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$3 billion in cancer drug waste: Can it be salvaged?
Three billion dollars: It’s enough to finance the annual out-of-pocket costs for 1 in 7 patients with cancer. It would cover almost half of the National Cancer Institute’s annual budget. And it could fund President Biden’s entire Cancer Moonshot program, with more than a billion to spare.
It’s also how much the United States spends on unused cancer drugs each year, some experts estimate.
Drug companies typically sell infused drugs in one or two single-dose vial sizes, but patients don’t come in such neat packages. A patient may need 300 mg of a drug that is only sold as 200 mg vials, which means half of a vial will go to waste.
Although most oncology drugs don’t incur substantial waste, even small volumes can translate to millions of dollars a year.
But can this money be saved or reallocated, if only we delivered drugs more efficiently?
Some experts don’t believe that’s possible.
“Attempts to recoup money for discarded drugs wouldn’t happen in a vacuum,” said Robin Yabroff, PhD, MBA, an epidemiologist and scientific vice president of Health Services Research at the American Cancer Society, who was part of a committee commissioned to evaluate the costs associated with discarded drugs.
The potential catch of any widespread effort to seek repayment or reduce the amount of discarded drugs, Dr. Yabroff and colleagues note, is that manufacturers would “simply increase the price of the vial.”
In other words, attempting to fix one problem may lead to another — essentially a whack-a-mole of cancer costs, which are projected to balloon to $246 billion by 2030.
What this means is without sweeping policies to rein in cancer care costs, oncologists can only do so much. And every little bit counts.
“We are left chipping away at this monster of cancer care costs,” said Adam Binder, MD, a medical oncologist at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia.
Millions spent on “reasonable amount” of waste
Michal Sarfaty, MD, was excited when enfortumab vedotin came on the market to treat advanced urothelial cancer in late 2019.
The cost of the drug, however, tempered her enthusiasm.
Enfortumab vedotin is a “great drug,” said Dr. Sarfaty, an oncologist at the Sheba Medical Center, Ramat Gan, Israel. But it can cost upwards of $500,000 a year for an average-weight man.
Given the expense, Dr. Sarfaty wanted to understand how much of the drug gets thrown away. During a fellowship at Memorial Sloan Kettering (MSK) Cancer Center in New York, Dr. Sarfaty explored the amount of unused enfortumab vedotin among the 64 patients who received the drug in 2020. She, along with a team at MSK, calculated the price tag of that waste and extrapolated those estimates for patients across the country.
Although waste occurred in almost half of administered doses (367 of 793), only a small volume got discarded — 2.9% per dose, on average.
Multiplying unused milligrams by the cost per milligram, Dr. Sarfaty and colleagues estimated that, for each patient, $3,127 of the drug got discarded. When calculated over the year, the cost came to just over $200,000 at MSK, and nearly $15 million when projected across the approved patient population in the United States.
“Ultimately, we did not see a lot of waste with this specific drug,” Dr. Sarfaty said. “Under 2.9% is considered a reasonable amount, below the 3% threshold Peter Bach, MD, and colleagues recommend. But even with this small amount of waste, the cost per patient and to the system remains notable.”
The problem with recouping drug waste
Estimates from the Centers for Medicare & Medicaid Services (CMS), which tracks costs associated with discarded weight-based drugs covered under Medicare Part B, support the notion that small quantities of discarded drugs can still translate to big bucks.
Since 2017, CMS has required healthcare providers to report the volume of drugs discarded from a single-dose vial using a code, known as the JW modifier. The JW modifier means that providers can be reimbursed for the entire vial amount, not just the quantity the patient used.
In 2019, claims data from Medicare Part B showed that 1.85% of discarded rituximab came to $33.3 million. For infliximab, the 1.55% of discarded liquid translated to $15 million, and just 0.36% of discarded pembrolizumab reached $10 million.
However, experts question whether the JW modifier accurately reflects the quantity of drugs discarded.
According to the 2021 report from the National Academies of Sciences, Engineering, and Medicine (NASEM), most physicians don’t use the JW modifier. Among Medicare claims, 16.2% included the JW modifier in 2017 and 16.9% did in 2018.
The rate was significantly lower for private insurance. Of more than 4 million private insurance claims on 77 drugs made in 2017 and 2018, only 3.6% included the JW modifier; 15 of these drugs had no JW claims.
“Although we found that most physicians don’t use the JW modifier, even those who do, don’t use it consistently, even for the same patient,” said Dr. Yabroff, a co-author on the report.
Going a step further, Dr. Yabroff and colleagues argue that even if everyone used the JW modifier as intended, manufacturers would probably increase the price of drugs to compensate for any loss, potentially eliminating savings for payers.
That’s because, in the United States, manufacturers typically base drug prices on a patient and payers’ “willingness to pay for better health,” not on the volume of liquid used. Take a patient who pays $2,000 to receive the dose they need. If that dose is 600 mg but requires using two vials of 400 mg, then “to the patient, the 600-mg dose is worth $2,000, and the remainder has no value whatsoever,” the NASEM authors argue.
The authors parallel this scenario to purchasing a designer coat or dress. If that item requires alterations that remove a section of material, “the customer does not typically get a rebate because all the fabric was not needed,” the NASEM team writes.
But there’s a flaw in this rationale, argues Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel. A person’s willingness to pay for better health assumes that the price of a drug is based on proper market forces, where a drug’s cost and its effectiveness are in harmony.
“The problem is we’re operating in a broken market where the prices of oncology drugs have no real bearing on their efficacy,” said Dr. Goldstein.
And, as Dr. Bach noted in a 2021 Health Affairs piece, willingness to pay also requires that consumers know what they’re paying and allows them to walk away from an excessively high price.
But neither is a reality.
For one, Dr. Bach explains, companies may lowball the monthly price of a drug. In 2020, GlaxoSmithKline (GSK) announced that its new drug Blenrep would carry a list price of $8,277 per vial, or about $23,900 per month for an average 79 kg (175 lb) patient. That price accounts for two vials of the drug. But, according to Dr. Bach, “what GSK left out is that 44% of U.S. adults weigh more than 80 kg, and above that weight, three vials are needed per dose.” That would raise the average monthly cost to $30,479.
Perhaps more importantly, consumers can’t easily walk away.
“Medicare can’t negotiate prices and is forced to pay what a drug company says,” Dr. Goldstein said. “This is very different to when I buy a coat. If the price is too high, I can walk away.”
Fixed dosing: A solution or a new problem?
Efforts to reduce the financial impact of discarded cancer drugs can blow back on physicians, patients, and payers in other unanticipated ways. Take fixed dosing. Although chemotherapy dosing remains weight-based, many targeted therapies — such as nivolumab and pembrolizumab — recently transitioned to a fixed dosing regimen.
Administering a fixed, instead of weight-based, dose eliminates waste but can create new problems.
“Patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” said Dr. Goldstein. In a 2017 analysis, Dr. Goldstein and colleagues compared dosing strategies in patients with metastatic non–small cell lung cancer who received pembrolizumab. The team found that the total annual cost of weight-based dosing was $2.6 billion, whereas the cost of the fixed dosing strategy was $3.44 billion — 24% more. In other words, personalized weight-based dosing would save more than $825 million dollars in the United States each year.
A 2020 analysis based in France found a similar cost increase of 26% for fixed dosing of pembrolizumab as well as nivolumab.
“I’ve argued we should go back to weight-based dosing,” Dr. Goldstein said. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”
Does dose rounding work?
Rose DiMarco, PharmD, BCPS, BCOP, keeps a tight watch on patients being treated at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia.
Dr. DiMarco educates patients about their treatment plan, reviews their lab results, and monitors them for side effects and drug interactions.
She also thinks a lot about costs.
“We spend about $100,000 a day on oncology drugs, and we want to make sure we’re not being wasteful,” Dr. DiMarco said in an interview.
One major initiative to curb waste and reduce costs at Jefferson has centered on dose rounding, which calculates whether a specific dose can be altered slightly to conserve vials and prevent waste. According to the Hematology/Oncology Pharmacy Association, a patient can receive up to 10% more or less of a weight-based dose without impacting treatment efficacy.
If, for instance, a patient requires 380 mg, but two vials come to 400 mg, rounding up that dose by approximately 5% means eliminating 20 mg that would go unused. But if that patient requires 420 mg, rounding down about 5% means substantial savings from not opening a new vial.
At Jefferson, Dr. DiMarco and her pharmacy colleagues map out dose ranges for all patients. Anyone who falls inside the 10% may be eligible for dose rounding. Anyone who doesn’t will receive the usual dose.
Although it is a challenge to implement, dose rounding has become standard of care at many cancer centers across the United States and is linked to substantial savings.
A 2018 analysis projected annual savings of $865,000 associated with rounding down eight monoclonal antibodies for patients with metastatic disease at a community cancer center. A more recent analysis from the Mayo Clinic found that dose rounding saved a total of 9,814 drug vials — 4485 of which were cancer drugs and 5329 of which were biologics — and resulted in $7.3 million in savings over 6 months in 2019 — $1.56 million from oncology agents and $5.7 from biologics.
And in a small 2019 analysis, researchers at Jefferson showed dose rounding of one monoclonal antibody saved approximately $30,000 in just 3 months, Dr. DiMarco noted.
“Not only does this process reduce costs and waste, but it also standardizes the preparation of hazardous medications, which can help prevent medication errors,” Dr. DiMarco said.
Nibbling around the edges
Despite estimates that scale into the billions of dollars, “drug wastage is just a small part of overall cancer costs,” Dr. Sarfaty said.
Fumiko Chino, MD, a radiation oncologist at MSK, agrees. “When we talk about affordability and cost, we can nibble around the edges of what’s really important,” Dr. Chino said. “Discarded drugs may cost a lot when you consider them in aggregate, but they are not as important as negotiated drug prices, which could substantially reduce overall costs.”
And until drug prices are addressed on a broader policy level, the cost of cancer care likely won’t improve in a meaningful way.
“But for the patient sitting in front of me, my focus will always be to provide the best care possible,” Dr. Binder said.
A version of this article first appeared on Medscape.com.
Three billion dollars: It’s enough to finance the annual out-of-pocket costs for 1 in 7 patients with cancer. It would cover almost half of the National Cancer Institute’s annual budget. And it could fund President Biden’s entire Cancer Moonshot program, with more than a billion to spare.
It’s also how much the United States spends on unused cancer drugs each year, some experts estimate.
Drug companies typically sell infused drugs in one or two single-dose vial sizes, but patients don’t come in such neat packages. A patient may need 300 mg of a drug that is only sold as 200 mg vials, which means half of a vial will go to waste.
Although most oncology drugs don’t incur substantial waste, even small volumes can translate to millions of dollars a year.
But can this money be saved or reallocated, if only we delivered drugs more efficiently?
Some experts don’t believe that’s possible.
“Attempts to recoup money for discarded drugs wouldn’t happen in a vacuum,” said Robin Yabroff, PhD, MBA, an epidemiologist and scientific vice president of Health Services Research at the American Cancer Society, who was part of a committee commissioned to evaluate the costs associated with discarded drugs.
The potential catch of any widespread effort to seek repayment or reduce the amount of discarded drugs, Dr. Yabroff and colleagues note, is that manufacturers would “simply increase the price of the vial.”
In other words, attempting to fix one problem may lead to another — essentially a whack-a-mole of cancer costs, which are projected to balloon to $246 billion by 2030.
What this means is without sweeping policies to rein in cancer care costs, oncologists can only do so much. And every little bit counts.
“We are left chipping away at this monster of cancer care costs,” said Adam Binder, MD, a medical oncologist at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia.
Millions spent on “reasonable amount” of waste
Michal Sarfaty, MD, was excited when enfortumab vedotin came on the market to treat advanced urothelial cancer in late 2019.
The cost of the drug, however, tempered her enthusiasm.
Enfortumab vedotin is a “great drug,” said Dr. Sarfaty, an oncologist at the Sheba Medical Center, Ramat Gan, Israel. But it can cost upwards of $500,000 a year for an average-weight man.
Given the expense, Dr. Sarfaty wanted to understand how much of the drug gets thrown away. During a fellowship at Memorial Sloan Kettering (MSK) Cancer Center in New York, Dr. Sarfaty explored the amount of unused enfortumab vedotin among the 64 patients who received the drug in 2020. She, along with a team at MSK, calculated the price tag of that waste and extrapolated those estimates for patients across the country.
Although waste occurred in almost half of administered doses (367 of 793), only a small volume got discarded — 2.9% per dose, on average.
Multiplying unused milligrams by the cost per milligram, Dr. Sarfaty and colleagues estimated that, for each patient, $3,127 of the drug got discarded. When calculated over the year, the cost came to just over $200,000 at MSK, and nearly $15 million when projected across the approved patient population in the United States.
“Ultimately, we did not see a lot of waste with this specific drug,” Dr. Sarfaty said. “Under 2.9% is considered a reasonable amount, below the 3% threshold Peter Bach, MD, and colleagues recommend. But even with this small amount of waste, the cost per patient and to the system remains notable.”
The problem with recouping drug waste
Estimates from the Centers for Medicare & Medicaid Services (CMS), which tracks costs associated with discarded weight-based drugs covered under Medicare Part B, support the notion that small quantities of discarded drugs can still translate to big bucks.
Since 2017, CMS has required healthcare providers to report the volume of drugs discarded from a single-dose vial using a code, known as the JW modifier. The JW modifier means that providers can be reimbursed for the entire vial amount, not just the quantity the patient used.
In 2019, claims data from Medicare Part B showed that 1.85% of discarded rituximab came to $33.3 million. For infliximab, the 1.55% of discarded liquid translated to $15 million, and just 0.36% of discarded pembrolizumab reached $10 million.
However, experts question whether the JW modifier accurately reflects the quantity of drugs discarded.
According to the 2021 report from the National Academies of Sciences, Engineering, and Medicine (NASEM), most physicians don’t use the JW modifier. Among Medicare claims, 16.2% included the JW modifier in 2017 and 16.9% did in 2018.
The rate was significantly lower for private insurance. Of more than 4 million private insurance claims on 77 drugs made in 2017 and 2018, only 3.6% included the JW modifier; 15 of these drugs had no JW claims.
“Although we found that most physicians don’t use the JW modifier, even those who do, don’t use it consistently, even for the same patient,” said Dr. Yabroff, a co-author on the report.
Going a step further, Dr. Yabroff and colleagues argue that even if everyone used the JW modifier as intended, manufacturers would probably increase the price of drugs to compensate for any loss, potentially eliminating savings for payers.
That’s because, in the United States, manufacturers typically base drug prices on a patient and payers’ “willingness to pay for better health,” not on the volume of liquid used. Take a patient who pays $2,000 to receive the dose they need. If that dose is 600 mg but requires using two vials of 400 mg, then “to the patient, the 600-mg dose is worth $2,000, and the remainder has no value whatsoever,” the NASEM authors argue.
The authors parallel this scenario to purchasing a designer coat or dress. If that item requires alterations that remove a section of material, “the customer does not typically get a rebate because all the fabric was not needed,” the NASEM team writes.
But there’s a flaw in this rationale, argues Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel. A person’s willingness to pay for better health assumes that the price of a drug is based on proper market forces, where a drug’s cost and its effectiveness are in harmony.
“The problem is we’re operating in a broken market where the prices of oncology drugs have no real bearing on their efficacy,” said Dr. Goldstein.
And, as Dr. Bach noted in a 2021 Health Affairs piece, willingness to pay also requires that consumers know what they’re paying and allows them to walk away from an excessively high price.
But neither is a reality.
For one, Dr. Bach explains, companies may lowball the monthly price of a drug. In 2020, GlaxoSmithKline (GSK) announced that its new drug Blenrep would carry a list price of $8,277 per vial, or about $23,900 per month for an average 79 kg (175 lb) patient. That price accounts for two vials of the drug. But, according to Dr. Bach, “what GSK left out is that 44% of U.S. adults weigh more than 80 kg, and above that weight, three vials are needed per dose.” That would raise the average monthly cost to $30,479.
Perhaps more importantly, consumers can’t easily walk away.
“Medicare can’t negotiate prices and is forced to pay what a drug company says,” Dr. Goldstein said. “This is very different to when I buy a coat. If the price is too high, I can walk away.”
Fixed dosing: A solution or a new problem?
Efforts to reduce the financial impact of discarded cancer drugs can blow back on physicians, patients, and payers in other unanticipated ways. Take fixed dosing. Although chemotherapy dosing remains weight-based, many targeted therapies — such as nivolumab and pembrolizumab — recently transitioned to a fixed dosing regimen.
Administering a fixed, instead of weight-based, dose eliminates waste but can create new problems.
“Patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” said Dr. Goldstein. In a 2017 analysis, Dr. Goldstein and colleagues compared dosing strategies in patients with metastatic non–small cell lung cancer who received pembrolizumab. The team found that the total annual cost of weight-based dosing was $2.6 billion, whereas the cost of the fixed dosing strategy was $3.44 billion — 24% more. In other words, personalized weight-based dosing would save more than $825 million dollars in the United States each year.
A 2020 analysis based in France found a similar cost increase of 26% for fixed dosing of pembrolizumab as well as nivolumab.
“I’ve argued we should go back to weight-based dosing,” Dr. Goldstein said. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”
Does dose rounding work?
Rose DiMarco, PharmD, BCPS, BCOP, keeps a tight watch on patients being treated at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia.
Dr. DiMarco educates patients about their treatment plan, reviews their lab results, and monitors them for side effects and drug interactions.
She also thinks a lot about costs.
“We spend about $100,000 a day on oncology drugs, and we want to make sure we’re not being wasteful,” Dr. DiMarco said in an interview.
One major initiative to curb waste and reduce costs at Jefferson has centered on dose rounding, which calculates whether a specific dose can be altered slightly to conserve vials and prevent waste. According to the Hematology/Oncology Pharmacy Association, a patient can receive up to 10% more or less of a weight-based dose without impacting treatment efficacy.
If, for instance, a patient requires 380 mg, but two vials come to 400 mg, rounding up that dose by approximately 5% means eliminating 20 mg that would go unused. But if that patient requires 420 mg, rounding down about 5% means substantial savings from not opening a new vial.
At Jefferson, Dr. DiMarco and her pharmacy colleagues map out dose ranges for all patients. Anyone who falls inside the 10% may be eligible for dose rounding. Anyone who doesn’t will receive the usual dose.
Although it is a challenge to implement, dose rounding has become standard of care at many cancer centers across the United States and is linked to substantial savings.
A 2018 analysis projected annual savings of $865,000 associated with rounding down eight monoclonal antibodies for patients with metastatic disease at a community cancer center. A more recent analysis from the Mayo Clinic found that dose rounding saved a total of 9,814 drug vials — 4485 of which were cancer drugs and 5329 of which were biologics — and resulted in $7.3 million in savings over 6 months in 2019 — $1.56 million from oncology agents and $5.7 from biologics.
And in a small 2019 analysis, researchers at Jefferson showed dose rounding of one monoclonal antibody saved approximately $30,000 in just 3 months, Dr. DiMarco noted.
“Not only does this process reduce costs and waste, but it also standardizes the preparation of hazardous medications, which can help prevent medication errors,” Dr. DiMarco said.
Nibbling around the edges
Despite estimates that scale into the billions of dollars, “drug wastage is just a small part of overall cancer costs,” Dr. Sarfaty said.
Fumiko Chino, MD, a radiation oncologist at MSK, agrees. “When we talk about affordability and cost, we can nibble around the edges of what’s really important,” Dr. Chino said. “Discarded drugs may cost a lot when you consider them in aggregate, but they are not as important as negotiated drug prices, which could substantially reduce overall costs.”
And until drug prices are addressed on a broader policy level, the cost of cancer care likely won’t improve in a meaningful way.
“But for the patient sitting in front of me, my focus will always be to provide the best care possible,” Dr. Binder said.
A version of this article first appeared on Medscape.com.
Three billion dollars: It’s enough to finance the annual out-of-pocket costs for 1 in 7 patients with cancer. It would cover almost half of the National Cancer Institute’s annual budget. And it could fund President Biden’s entire Cancer Moonshot program, with more than a billion to spare.
It’s also how much the United States spends on unused cancer drugs each year, some experts estimate.
Drug companies typically sell infused drugs in one or two single-dose vial sizes, but patients don’t come in such neat packages. A patient may need 300 mg of a drug that is only sold as 200 mg vials, which means half of a vial will go to waste.
Although most oncology drugs don’t incur substantial waste, even small volumes can translate to millions of dollars a year.
But can this money be saved or reallocated, if only we delivered drugs more efficiently?
Some experts don’t believe that’s possible.
“Attempts to recoup money for discarded drugs wouldn’t happen in a vacuum,” said Robin Yabroff, PhD, MBA, an epidemiologist and scientific vice president of Health Services Research at the American Cancer Society, who was part of a committee commissioned to evaluate the costs associated with discarded drugs.
The potential catch of any widespread effort to seek repayment or reduce the amount of discarded drugs, Dr. Yabroff and colleagues note, is that manufacturers would “simply increase the price of the vial.”
In other words, attempting to fix one problem may lead to another — essentially a whack-a-mole of cancer costs, which are projected to balloon to $246 billion by 2030.
What this means is without sweeping policies to rein in cancer care costs, oncologists can only do so much. And every little bit counts.
“We are left chipping away at this monster of cancer care costs,” said Adam Binder, MD, a medical oncologist at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia.
Millions spent on “reasonable amount” of waste
Michal Sarfaty, MD, was excited when enfortumab vedotin came on the market to treat advanced urothelial cancer in late 2019.
The cost of the drug, however, tempered her enthusiasm.
Enfortumab vedotin is a “great drug,” said Dr. Sarfaty, an oncologist at the Sheba Medical Center, Ramat Gan, Israel. But it can cost upwards of $500,000 a year for an average-weight man.
Given the expense, Dr. Sarfaty wanted to understand how much of the drug gets thrown away. During a fellowship at Memorial Sloan Kettering (MSK) Cancer Center in New York, Dr. Sarfaty explored the amount of unused enfortumab vedotin among the 64 patients who received the drug in 2020. She, along with a team at MSK, calculated the price tag of that waste and extrapolated those estimates for patients across the country.
Although waste occurred in almost half of administered doses (367 of 793), only a small volume got discarded — 2.9% per dose, on average.
Multiplying unused milligrams by the cost per milligram, Dr. Sarfaty and colleagues estimated that, for each patient, $3,127 of the drug got discarded. When calculated over the year, the cost came to just over $200,000 at MSK, and nearly $15 million when projected across the approved patient population in the United States.
“Ultimately, we did not see a lot of waste with this specific drug,” Dr. Sarfaty said. “Under 2.9% is considered a reasonable amount, below the 3% threshold Peter Bach, MD, and colleagues recommend. But even with this small amount of waste, the cost per patient and to the system remains notable.”
The problem with recouping drug waste
Estimates from the Centers for Medicare & Medicaid Services (CMS), which tracks costs associated with discarded weight-based drugs covered under Medicare Part B, support the notion that small quantities of discarded drugs can still translate to big bucks.
Since 2017, CMS has required healthcare providers to report the volume of drugs discarded from a single-dose vial using a code, known as the JW modifier. The JW modifier means that providers can be reimbursed for the entire vial amount, not just the quantity the patient used.
In 2019, claims data from Medicare Part B showed that 1.85% of discarded rituximab came to $33.3 million. For infliximab, the 1.55% of discarded liquid translated to $15 million, and just 0.36% of discarded pembrolizumab reached $10 million.
However, experts question whether the JW modifier accurately reflects the quantity of drugs discarded.
According to the 2021 report from the National Academies of Sciences, Engineering, and Medicine (NASEM), most physicians don’t use the JW modifier. Among Medicare claims, 16.2% included the JW modifier in 2017 and 16.9% did in 2018.
The rate was significantly lower for private insurance. Of more than 4 million private insurance claims on 77 drugs made in 2017 and 2018, only 3.6% included the JW modifier; 15 of these drugs had no JW claims.
“Although we found that most physicians don’t use the JW modifier, even those who do, don’t use it consistently, even for the same patient,” said Dr. Yabroff, a co-author on the report.
Going a step further, Dr. Yabroff and colleagues argue that even if everyone used the JW modifier as intended, manufacturers would probably increase the price of drugs to compensate for any loss, potentially eliminating savings for payers.
That’s because, in the United States, manufacturers typically base drug prices on a patient and payers’ “willingness to pay for better health,” not on the volume of liquid used. Take a patient who pays $2,000 to receive the dose they need. If that dose is 600 mg but requires using two vials of 400 mg, then “to the patient, the 600-mg dose is worth $2,000, and the remainder has no value whatsoever,” the NASEM authors argue.
The authors parallel this scenario to purchasing a designer coat or dress. If that item requires alterations that remove a section of material, “the customer does not typically get a rebate because all the fabric was not needed,” the NASEM team writes.
But there’s a flaw in this rationale, argues Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel. A person’s willingness to pay for better health assumes that the price of a drug is based on proper market forces, where a drug’s cost and its effectiveness are in harmony.
“The problem is we’re operating in a broken market where the prices of oncology drugs have no real bearing on their efficacy,” said Dr. Goldstein.
And, as Dr. Bach noted in a 2021 Health Affairs piece, willingness to pay also requires that consumers know what they’re paying and allows them to walk away from an excessively high price.
But neither is a reality.
For one, Dr. Bach explains, companies may lowball the monthly price of a drug. In 2020, GlaxoSmithKline (GSK) announced that its new drug Blenrep would carry a list price of $8,277 per vial, or about $23,900 per month for an average 79 kg (175 lb) patient. That price accounts for two vials of the drug. But, according to Dr. Bach, “what GSK left out is that 44% of U.S. adults weigh more than 80 kg, and above that weight, three vials are needed per dose.” That would raise the average monthly cost to $30,479.
Perhaps more importantly, consumers can’t easily walk away.
“Medicare can’t negotiate prices and is forced to pay what a drug company says,” Dr. Goldstein said. “This is very different to when I buy a coat. If the price is too high, I can walk away.”
Fixed dosing: A solution or a new problem?
Efforts to reduce the financial impact of discarded cancer drugs can blow back on physicians, patients, and payers in other unanticipated ways. Take fixed dosing. Although chemotherapy dosing remains weight-based, many targeted therapies — such as nivolumab and pembrolizumab — recently transitioned to a fixed dosing regimen.
Administering a fixed, instead of weight-based, dose eliminates waste but can create new problems.
“Patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” said Dr. Goldstein. In a 2017 analysis, Dr. Goldstein and colleagues compared dosing strategies in patients with metastatic non–small cell lung cancer who received pembrolizumab. The team found that the total annual cost of weight-based dosing was $2.6 billion, whereas the cost of the fixed dosing strategy was $3.44 billion — 24% more. In other words, personalized weight-based dosing would save more than $825 million dollars in the United States each year.
A 2020 analysis based in France found a similar cost increase of 26% for fixed dosing of pembrolizumab as well as nivolumab.
“I’ve argued we should go back to weight-based dosing,” Dr. Goldstein said. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”
Does dose rounding work?
Rose DiMarco, PharmD, BCPS, BCOP, keeps a tight watch on patients being treated at the Sidney Kimmel Cancer Center at Jefferson Health in Philadelphia.
Dr. DiMarco educates patients about their treatment plan, reviews their lab results, and monitors them for side effects and drug interactions.
She also thinks a lot about costs.
“We spend about $100,000 a day on oncology drugs, and we want to make sure we’re not being wasteful,” Dr. DiMarco said in an interview.
One major initiative to curb waste and reduce costs at Jefferson has centered on dose rounding, which calculates whether a specific dose can be altered slightly to conserve vials and prevent waste. According to the Hematology/Oncology Pharmacy Association, a patient can receive up to 10% more or less of a weight-based dose without impacting treatment efficacy.
If, for instance, a patient requires 380 mg, but two vials come to 400 mg, rounding up that dose by approximately 5% means eliminating 20 mg that would go unused. But if that patient requires 420 mg, rounding down about 5% means substantial savings from not opening a new vial.
At Jefferson, Dr. DiMarco and her pharmacy colleagues map out dose ranges for all patients. Anyone who falls inside the 10% may be eligible for dose rounding. Anyone who doesn’t will receive the usual dose.
Although it is a challenge to implement, dose rounding has become standard of care at many cancer centers across the United States and is linked to substantial savings.
A 2018 analysis projected annual savings of $865,000 associated with rounding down eight monoclonal antibodies for patients with metastatic disease at a community cancer center. A more recent analysis from the Mayo Clinic found that dose rounding saved a total of 9,814 drug vials — 4485 of which were cancer drugs and 5329 of which were biologics — and resulted in $7.3 million in savings over 6 months in 2019 — $1.56 million from oncology agents and $5.7 from biologics.
And in a small 2019 analysis, researchers at Jefferson showed dose rounding of one monoclonal antibody saved approximately $30,000 in just 3 months, Dr. DiMarco noted.
“Not only does this process reduce costs and waste, but it also standardizes the preparation of hazardous medications, which can help prevent medication errors,” Dr. DiMarco said.
Nibbling around the edges
Despite estimates that scale into the billions of dollars, “drug wastage is just a small part of overall cancer costs,” Dr. Sarfaty said.
Fumiko Chino, MD, a radiation oncologist at MSK, agrees. “When we talk about affordability and cost, we can nibble around the edges of what’s really important,” Dr. Chino said. “Discarded drugs may cost a lot when you consider them in aggregate, but they are not as important as negotiated drug prices, which could substantially reduce overall costs.”
And until drug prices are addressed on a broader policy level, the cost of cancer care likely won’t improve in a meaningful way.
“But for the patient sitting in front of me, my focus will always be to provide the best care possible,” Dr. Binder said.
A version of this article first appeared on Medscape.com.
Artificial intelligence: The Netflix of cancer treatment
Chemotherapy, now streaming at just $15.99 a month!
It’s a lazy Sunday and you flip on Netflix, looking for something new to watch. There’s an almost-overwhelming number of shows out there, but right at the top of the recommended list is something that strikes your fancy right away. The algorithm behind the scenes is doing its job well, winnowing the universe of content right down to the few things you’ll find relevant, based on what you’ve watched and liked in the past.
Now, the almighty content algorithm is coming for something a little more useful than binge watching obscure 80s sitcoms: cancer treatment.
By plugging the fully sequenced genomes of nearly 10,000 patients with 33 different types of cancer into an algorithm powered by the same sort of artificial intelligence used by Netflix, researchers from London and San Diego found 21 common faults in the chromosomes of tumors, which they called copy number signatures. While cancer is a complex disease, when faults occur in those copy number signatures, the results were similar across the board. If X genetic defect occurs within a tumor, Y result will happen, even across cancer types. For example, tumors whose chromosomes had shattered and reformed had by far the worst disease outcomes.
The eventual hope is that, just as Netflix can predict what you’ll want to watch based on what you’ve already seen, oncologists will be able to predict the course of a cancer, based on the tumor’s early genetic traits, and get ahead of future genetic degradation to prevent the worst outcomes. A sort of “Oh, your tumor has enjoyed The Office. Might we suggest a treatment of 30 Rock” situation. Further research will be required to determine whether or not the cancer algorithm can get us part 2 of “Stranger Things 4” a week early.
Pay criminals, cut crime?
What is the best method for punishing those who commit wrongdoing? Fines? Jail time? Actually, no. A recent study says that financial compensation works best.
In other words, pay them for their actions. Really.
Psychologist Tage S. Rai, PhD, of the University of California, San Diego, Rady School of Management, found that people who hurt others or commit crimes are actually doing it because they think it’s the right thing to do. The results of this study say play at the angle of their morality. When that’s compromised, the offender is less likely to do it again.
Four different experiments were conducted using an online economics game with nearly 1,500 participants. Dr. Rai found that providing a monetary bonus for inflicting a punishment on a third party within the game cut the participants’ willingness to do it again by 50%.
“People punish others to signal their own goodness and receiving compensation might make it seem as though they’re driven by greed rather than justice,” he said.
The big deterrent, though, was negative judgment from peers. People in the study were even more hesitant to inflict harm and gain a profit if they thought they were going to be judged for it.
So maybe the answer to cutting crime isn’t as simple as slapping on a fine. It’s slapping on shame and paying them for it.
A conspiracy of chronobiologic proportions
The Golden State Warriors just won the NBA championship – that much is true – but we’ve got some news that you didn’t get from ESPN. The kind of news that their “partners” from the NBA didn’t want them to report. Unlike most conspiracy theories, however, this one has some science behind it.
In this case, science in the form of a study published in Frontiers in Physiology says that jet lag had a greater effect on the Boston Celtics than it did on the Warriors.
“Eastward travel – where the destination time is later than the origin time – requires the athlete to shorten their day (known as a phase advance). During phase advance, athletes often struggle to fall asleep at an earlier bedtime, leading to sleep loss and, consequently, potential impaired physiological performance and motivation the next day,” senior author Elise Facer-Childs, PhD, of Monash University, Melbourne, said in written statement.
Dr. Facer-Childs and associates took a very close look at 10 seasons’ worth of NBA games – 11,481 games, to be exact – and found “that eastward (but not westward) jet lag was associated with impaired performance for home (but not away) teams.” The existence of a pro-Western bias against teams that traveled eastward for their home games was clear:
- The chance of winning for eastern teams was reduced by 6.0%.
- They grabbed 1.3 fewer rebounds per game.
- Their field goal percentage was 1.2% lower.
And here’s the final nail in the conspiracy coffin: The NBA knew about the jet lag effect and changed the schedule of the finals in 2014 in a way that makes it worse. Before that, the higher-seeded team got two home games, then the lower-seeded team had three at home, followed by two more at the home of the higher seed. Now it’s a 2-2-1-1-1 arrangement that leads to more travel and, of course, more jet lag.
The study was published during the championship series, so the investigators suggested that the Celtics “might benefit from chronobiology-informed strategies designed to mitigate eastward jet lag symptomatology.”
So there you have it, sports fans/conspiracy theorists: You can’t chase Steph Curry around the court for 48 minutes without the right chronobiology-informed strategy. Everyone knows that.
Being hungry can alter your ‘type’
Fasting and being hungry can be a dangerous mix for becoming “hangry” and irritable, but did you know being hungry can also affect your attraction to other people?
Evidence has shown that being hungry can affect important things such as decision-making, memory, cognition, and function. It might affect decision-making in the sense that those six tacos at Taco Bell might win out over grilled chicken breast and veggies at home, but can hunger make you think that the person you just swiped right on isn’t really your type after all?
We’ll leave that up to Valentina Cazzato of Liverpool (England) John Moores University and associates, whose study involved 44 people, of whom 21 were women in their early 20s. The participants were shown computer-generated images of men and women of different sizes. The same background was used for each picture and all the expressions of the models were neutral. Participants were asked to rate each image on how much they liked it. One study was done on participants who had been fasting for 12 hours, and the second was done on those who had just eaten something.
The subjects generally preferred slim models over more rounded ones, but not after fasting. When they were hungry, they found the round human bodies and faces more attractive. So, yes, it’s definitely possible that hunger can alter your attraction to others.
“Future work might seek to elucidate the relationship between physiological states of hunger and shifts in appreciation of the human bodies and whether this relationship might be mediated by individual traits associated with to beholder’s body adiposity,” said researchers.
Chemotherapy, now streaming at just $15.99 a month!
It’s a lazy Sunday and you flip on Netflix, looking for something new to watch. There’s an almost-overwhelming number of shows out there, but right at the top of the recommended list is something that strikes your fancy right away. The algorithm behind the scenes is doing its job well, winnowing the universe of content right down to the few things you’ll find relevant, based on what you’ve watched and liked in the past.
Now, the almighty content algorithm is coming for something a little more useful than binge watching obscure 80s sitcoms: cancer treatment.
By plugging the fully sequenced genomes of nearly 10,000 patients with 33 different types of cancer into an algorithm powered by the same sort of artificial intelligence used by Netflix, researchers from London and San Diego found 21 common faults in the chromosomes of tumors, which they called copy number signatures. While cancer is a complex disease, when faults occur in those copy number signatures, the results were similar across the board. If X genetic defect occurs within a tumor, Y result will happen, even across cancer types. For example, tumors whose chromosomes had shattered and reformed had by far the worst disease outcomes.
The eventual hope is that, just as Netflix can predict what you’ll want to watch based on what you’ve already seen, oncologists will be able to predict the course of a cancer, based on the tumor’s early genetic traits, and get ahead of future genetic degradation to prevent the worst outcomes. A sort of “Oh, your tumor has enjoyed The Office. Might we suggest a treatment of 30 Rock” situation. Further research will be required to determine whether or not the cancer algorithm can get us part 2 of “Stranger Things 4” a week early.
Pay criminals, cut crime?
What is the best method for punishing those who commit wrongdoing? Fines? Jail time? Actually, no. A recent study says that financial compensation works best.
In other words, pay them for their actions. Really.
Psychologist Tage S. Rai, PhD, of the University of California, San Diego, Rady School of Management, found that people who hurt others or commit crimes are actually doing it because they think it’s the right thing to do. The results of this study say play at the angle of their morality. When that’s compromised, the offender is less likely to do it again.
Four different experiments were conducted using an online economics game with nearly 1,500 participants. Dr. Rai found that providing a monetary bonus for inflicting a punishment on a third party within the game cut the participants’ willingness to do it again by 50%.
“People punish others to signal their own goodness and receiving compensation might make it seem as though they’re driven by greed rather than justice,” he said.
The big deterrent, though, was negative judgment from peers. People in the study were even more hesitant to inflict harm and gain a profit if they thought they were going to be judged for it.
So maybe the answer to cutting crime isn’t as simple as slapping on a fine. It’s slapping on shame and paying them for it.
A conspiracy of chronobiologic proportions
The Golden State Warriors just won the NBA championship – that much is true – but we’ve got some news that you didn’t get from ESPN. The kind of news that their “partners” from the NBA didn’t want them to report. Unlike most conspiracy theories, however, this one has some science behind it.
In this case, science in the form of a study published in Frontiers in Physiology says that jet lag had a greater effect on the Boston Celtics than it did on the Warriors.
“Eastward travel – where the destination time is later than the origin time – requires the athlete to shorten their day (known as a phase advance). During phase advance, athletes often struggle to fall asleep at an earlier bedtime, leading to sleep loss and, consequently, potential impaired physiological performance and motivation the next day,” senior author Elise Facer-Childs, PhD, of Monash University, Melbourne, said in written statement.
Dr. Facer-Childs and associates took a very close look at 10 seasons’ worth of NBA games – 11,481 games, to be exact – and found “that eastward (but not westward) jet lag was associated with impaired performance for home (but not away) teams.” The existence of a pro-Western bias against teams that traveled eastward for their home games was clear:
- The chance of winning for eastern teams was reduced by 6.0%.
- They grabbed 1.3 fewer rebounds per game.
- Their field goal percentage was 1.2% lower.
And here’s the final nail in the conspiracy coffin: The NBA knew about the jet lag effect and changed the schedule of the finals in 2014 in a way that makes it worse. Before that, the higher-seeded team got two home games, then the lower-seeded team had three at home, followed by two more at the home of the higher seed. Now it’s a 2-2-1-1-1 arrangement that leads to more travel and, of course, more jet lag.
The study was published during the championship series, so the investigators suggested that the Celtics “might benefit from chronobiology-informed strategies designed to mitigate eastward jet lag symptomatology.”
So there you have it, sports fans/conspiracy theorists: You can’t chase Steph Curry around the court for 48 minutes without the right chronobiology-informed strategy. Everyone knows that.
Being hungry can alter your ‘type’
Fasting and being hungry can be a dangerous mix for becoming “hangry” and irritable, but did you know being hungry can also affect your attraction to other people?
Evidence has shown that being hungry can affect important things such as decision-making, memory, cognition, and function. It might affect decision-making in the sense that those six tacos at Taco Bell might win out over grilled chicken breast and veggies at home, but can hunger make you think that the person you just swiped right on isn’t really your type after all?
We’ll leave that up to Valentina Cazzato of Liverpool (England) John Moores University and associates, whose study involved 44 people, of whom 21 were women in their early 20s. The participants were shown computer-generated images of men and women of different sizes. The same background was used for each picture and all the expressions of the models were neutral. Participants were asked to rate each image on how much they liked it. One study was done on participants who had been fasting for 12 hours, and the second was done on those who had just eaten something.
The subjects generally preferred slim models over more rounded ones, but not after fasting. When they were hungry, they found the round human bodies and faces more attractive. So, yes, it’s definitely possible that hunger can alter your attraction to others.
“Future work might seek to elucidate the relationship between physiological states of hunger and shifts in appreciation of the human bodies and whether this relationship might be mediated by individual traits associated with to beholder’s body adiposity,” said researchers.
Chemotherapy, now streaming at just $15.99 a month!
It’s a lazy Sunday and you flip on Netflix, looking for something new to watch. There’s an almost-overwhelming number of shows out there, but right at the top of the recommended list is something that strikes your fancy right away. The algorithm behind the scenes is doing its job well, winnowing the universe of content right down to the few things you’ll find relevant, based on what you’ve watched and liked in the past.
Now, the almighty content algorithm is coming for something a little more useful than binge watching obscure 80s sitcoms: cancer treatment.
By plugging the fully sequenced genomes of nearly 10,000 patients with 33 different types of cancer into an algorithm powered by the same sort of artificial intelligence used by Netflix, researchers from London and San Diego found 21 common faults in the chromosomes of tumors, which they called copy number signatures. While cancer is a complex disease, when faults occur in those copy number signatures, the results were similar across the board. If X genetic defect occurs within a tumor, Y result will happen, even across cancer types. For example, tumors whose chromosomes had shattered and reformed had by far the worst disease outcomes.
The eventual hope is that, just as Netflix can predict what you’ll want to watch based on what you’ve already seen, oncologists will be able to predict the course of a cancer, based on the tumor’s early genetic traits, and get ahead of future genetic degradation to prevent the worst outcomes. A sort of “Oh, your tumor has enjoyed The Office. Might we suggest a treatment of 30 Rock” situation. Further research will be required to determine whether or not the cancer algorithm can get us part 2 of “Stranger Things 4” a week early.
Pay criminals, cut crime?
What is the best method for punishing those who commit wrongdoing? Fines? Jail time? Actually, no. A recent study says that financial compensation works best.
In other words, pay them for their actions. Really.
Psychologist Tage S. Rai, PhD, of the University of California, San Diego, Rady School of Management, found that people who hurt others or commit crimes are actually doing it because they think it’s the right thing to do. The results of this study say play at the angle of their morality. When that’s compromised, the offender is less likely to do it again.
Four different experiments were conducted using an online economics game with nearly 1,500 participants. Dr. Rai found that providing a monetary bonus for inflicting a punishment on a third party within the game cut the participants’ willingness to do it again by 50%.
“People punish others to signal their own goodness and receiving compensation might make it seem as though they’re driven by greed rather than justice,” he said.
The big deterrent, though, was negative judgment from peers. People in the study were even more hesitant to inflict harm and gain a profit if they thought they were going to be judged for it.
So maybe the answer to cutting crime isn’t as simple as slapping on a fine. It’s slapping on shame and paying them for it.
A conspiracy of chronobiologic proportions
The Golden State Warriors just won the NBA championship – that much is true – but we’ve got some news that you didn’t get from ESPN. The kind of news that their “partners” from the NBA didn’t want them to report. Unlike most conspiracy theories, however, this one has some science behind it.
In this case, science in the form of a study published in Frontiers in Physiology says that jet lag had a greater effect on the Boston Celtics than it did on the Warriors.
“Eastward travel – where the destination time is later than the origin time – requires the athlete to shorten their day (known as a phase advance). During phase advance, athletes often struggle to fall asleep at an earlier bedtime, leading to sleep loss and, consequently, potential impaired physiological performance and motivation the next day,” senior author Elise Facer-Childs, PhD, of Monash University, Melbourne, said in written statement.
Dr. Facer-Childs and associates took a very close look at 10 seasons’ worth of NBA games – 11,481 games, to be exact – and found “that eastward (but not westward) jet lag was associated with impaired performance for home (but not away) teams.” The existence of a pro-Western bias against teams that traveled eastward for their home games was clear:
- The chance of winning for eastern teams was reduced by 6.0%.
- They grabbed 1.3 fewer rebounds per game.
- Their field goal percentage was 1.2% lower.
And here’s the final nail in the conspiracy coffin: The NBA knew about the jet lag effect and changed the schedule of the finals in 2014 in a way that makes it worse. Before that, the higher-seeded team got two home games, then the lower-seeded team had three at home, followed by two more at the home of the higher seed. Now it’s a 2-2-1-1-1 arrangement that leads to more travel and, of course, more jet lag.
The study was published during the championship series, so the investigators suggested that the Celtics “might benefit from chronobiology-informed strategies designed to mitigate eastward jet lag symptomatology.”
So there you have it, sports fans/conspiracy theorists: You can’t chase Steph Curry around the court for 48 minutes without the right chronobiology-informed strategy. Everyone knows that.
Being hungry can alter your ‘type’
Fasting and being hungry can be a dangerous mix for becoming “hangry” and irritable, but did you know being hungry can also affect your attraction to other people?
Evidence has shown that being hungry can affect important things such as decision-making, memory, cognition, and function. It might affect decision-making in the sense that those six tacos at Taco Bell might win out over grilled chicken breast and veggies at home, but can hunger make you think that the person you just swiped right on isn’t really your type after all?
We’ll leave that up to Valentina Cazzato of Liverpool (England) John Moores University and associates, whose study involved 44 people, of whom 21 were women in their early 20s. The participants were shown computer-generated images of men and women of different sizes. The same background was used for each picture and all the expressions of the models were neutral. Participants were asked to rate each image on how much they liked it. One study was done on participants who had been fasting for 12 hours, and the second was done on those who had just eaten something.
The subjects generally preferred slim models over more rounded ones, but not after fasting. When they were hungry, they found the round human bodies and faces more attractive. So, yes, it’s definitely possible that hunger can alter your attraction to others.
“Future work might seek to elucidate the relationship between physiological states of hunger and shifts in appreciation of the human bodies and whether this relationship might be mediated by individual traits associated with to beholder’s body adiposity,” said researchers.
Debated: Nonfactor versus gene therapy for hemophilia
Ultimately, results of a very informal polling of the online audience suggested a strong leaning toward the known benefits of nonfactor therapy, as opposed to as-yet unapproved gene therapy. Although Benjamin Samelson-Jones, MD, PhD, argued for gene therapy, he also saluted the progress made that had enabled such choices.
“Our patients and the field have greatly benefited from this broad spectrum of different therapies and how they’ve been implemented, and it’s a truly exciting time because there will continue to be advancements in both these therapeutic modalities in the next 5-10 years,” said Dr. Samelson-Jones, an assistant professor of pediatrics in the division of hematology at the Children’s Hospital of Philadelphia.
Game changers emerge
Hemophilia A, characterized by a hereditary deficiency in factor VIII disorder, has long involved prophylaxis treatment with procoagulant factor replacement therapy that requires intravenous injection as often as several times a week. This can cause problems with venous access that are particularly burdensome for child patients.
Nonfactor therapy, currently consisting of the approved emicizumab but with more agents in development, provides coagulation without replacement of factor VIII. Importantly, this treatment requires only subcutaneous injection which, after a loading dose period, may be needed weekly or even just once a month.
However, in 2018, at approximately the same time that emicizumab was approved, patients with hemophilia A became eligible to enroll in clinical trials for the far more revolutionary concept of gene therapy, with the chance to become infusion free after just a single infusion.
There are caveats aplenty. Four of the therapies now in phase 3 development are adeno-associated viral vectors that are liver directed, meaning that patients need to be closely followed in the first months post infusion, with regular blood tests and other monitoring.
Notably, once patients receive an infusion, they cannot receive another, because of the buildup of antibodies.
“I think [this is] most important when considering current gene therapy – a patient can only receive it once, based on current technology,” Dr. Samelson-Jones said in an interview.“That means if a patient received gene therapy in 2023, and something better is developed in 2025, they are unlikely to be able to receive it.”
Nevertheless, with favorable phase 3 data reported in March 2022 in the New England Journal of Medicine, the first gene therapy for hemophilia A, valoctocogene roxaparvovec (BioMarin), appears poised for possible regulatory approval very soon.
“I expect this product to be approved in the next year, though I been previously surprised before about delays in this product’s clinical development,” Dr. Samelson-Jones said.
Pros of nonfactor therapy
Arguing on the side of nonfactor therapy in the debate, Roseline d’Oiron, MD, underscored the extent to which nonfactor therapy has dramatically transformed lives.
With intravenous injections, “the burden of the stress and anxiety of the injections is underestimated, even when you don’t have venous access problems,” said Dr. d’Oiron, a clinician investigator at the University Paris XI.
The heavy toll that these therapeutic challenges have had on patients’ lives and identities has been documented in patient advocacy reports, underscoring that “the availability of subcutaneous therapies through the nonfactor therapies for hemophilia A has really been a game changer,” said Dr. d’Oiron, who is also the associate director of the Reference Centre for Hemophilia and Other Congenital Rare Bleeding Disorders, Congenital Platelets Disorders, and von Willebrand Disease at Bicêtre (France) Hospital AP-HP.
She noted that newer therapies in development show the potential to offer longer half-lives, providing “even more improvement with wider intervals between the subcutaneous injections.”
The efficacy of nonfactor therapies also translates to lower rates of joint bleeding, which represent the most common complication in hemophilia, potentially causing acute or chronic pain.
“These therapies allow a life that is much closer to what would be considered a normal life, and especially allowing some physical activities with the prevention of bleeding episodes,” Dr. d’Oiron said. “The drugs have a good safety profile and are completely changing the picture of this disease.”
Dr. d’Oiron noted that, in the real-world clinical setting, there is no debate over nonfactor versus gene therapy. Most prefer to stick with what is already working well for them.
“In my clinical practice, only a very limited number of patients are really willing and considering the switch to gene therapy,” she said. “They feel that the nonfactor therapy is filling their previous unmet needs quite well, and the impression is that we don’t necessarily need look for something different.”
Limitations of nonfactor therapy
Echoing that he has had the same favorable experiences with patients on emicizumab as described by Dr. d’Oiron, Dr. Samelson-Jones, pointed out key caveats that significantly differentiate it from gene therapy, not the least of which is the basic issue of the requirement of injections.
“Even with longer half-lives, approximately monthly injections are still required with nonfactor therapy,” which can – and have – been compromised by any range of societal disruptions, including a pandemic or supply issues.
Furthermore, the mechanism of nonfactor therapies in providing hemostatic regulation outside of normal factor VIII is unregulated, with ‘no easy ‘off’ switch,’ he explained.
“The balance that nonfactor agents provide between pro- and anticoagulant forces is inherently more fragile – more like a knife’s edge, and has resulted in the risk for thrombotic complications in most examples of nonfactor therapies,” he said.
In addition, the therapies have unknown immunogenicity, with an increased risk of the development of antidrug antibodies, called inhibitors, a theoretical complication of nonfactor therapies, if factor VIII is only administered in the setting of bleeds or perioperatively, Dr. Samelson-Jones said.
That being said, “nonfactor agents are not for all patients with hemophilia A in the future – but rather gene therapy is,” he noted.
Normal hemostasis ‘only achievable with gene therapy’
In contrast to nonfactor therapy, just one infusion of gene therapy “ideally offers many years of potentially curative hemostatic protection,” Dr. Samuelson-Jones said. “The ultimate goal, I believe, is to achieve normal hemostasis and health equity, and I contend this goal is only really achievable with gene therapy.”
He noted that, while gene therapies will require initial monitoring, “once the gene therapy recipient is 3 or 12 months out, the monitoring really de-escalates, and the patient is free from all drug delivery or needing to be in close contact with their treatment center.”
Regarding concerns about not being able to receive gene therapy more than once, Dr. Samuelson-Jones said that work is underway to develop alternative viral vectors and nonviral vectors that may overcome those challenges.
Overall, he underscored that challenges are par for the course in the development of any novel therapeutic approach.
For instance, similar challenges were experienced 10 years ago in the development of gene therapy for hemophilia B. However, with advances, “they’ve now been able to achieve long-term sustained levels in the normal ordinary curative range. And I’m optimistic that similar advances may be able to be achieved for factor VIII gene transfer,” he said.
Nonfactor therapies as bridge?
That being said, nonfactor therapies are going to be essential in treating patients until such advances come to fruition, Dr. Samelson-Jones noted.
“I would agree that nonfactor therapies in 2022 have really simplified and improved the convenience of prophylaxis,” he said, “but I would view them as a bridging therapy until gene therapy goes through clinical development and are licensed for all patients with hemophilia.”
While Dr. d’Oiron agreed with that possibility, she countered that, when it comes to crossing over to gene therapy, some very long bridges might be needed.
“I would love to have a therapy that would be both extremely safe and effective and offering a cure and normalization of hemostasis,” she said. “But I’m afraid that the current available gene therapy that might be arriving soon still does no fulfill all of these criteria. I think there are a lot of questions so far.”
Ultimately, Dr. Samelson-Jones conceded that the success of emicizumab has set a high bar in the minds of clinicians and patients alike, which will strongly influence perceptions of any alternative approaches –and of participation in clinical trials.
“I think that, unequivocally, emicizumab has changed the risk-benefit discussion about enrolling in clinical trials, and in gene therapy in particular,” he said. “And I think it also has set the threshold for efficacy – and if a gene therapy product in development can’t achieve bleeding control that is similar to that provided with emicizumab, then that is not a product that is going to be able to continue in clinical development.”
Importantly, both debaters underscored the need for ongoing efforts to make the novel – and therefore costly therapies accessible to all, through organizations including the World Federation of Hemophilia Humanitarian Aid Program.
“It would be my hope that we can then extend all of these great therapies to the majority of undertreated patients with hemophilia around the world,” Dr. Samelson-Jones said. “I think that’s an issue that must be addressed with all of these novel therapies.”
Commenting on these issues, Riitta Lassila, MD, professor of coagulation medicine at the Comprehensive Cancer Center at Helsinki University Hospital, , who moderated the debate, said it has also been her experience that some patients express reluctance to enter the gene therapy trials
“There are two groups of patients, just as in the healthy population as well,” she said in an interview. “Some more ready to take risks and some are very hesitant [regarding] anything new. We do have the saying: If something is not broken, don’t fix it.”
She noted the additional concern that while the therapy has been successful in hemophilia B, factor VIII involves a larger construct and may have limitations with hemophilia A.
Furthermore, “the sustainability of factor VIII production may decrease in a couple of years, and the treatment duration could remain suboptimal,” Dr. Lassila said. “However, hemostasis seems to still [be achieved] with gene therapy, so maybe there will be more efficient solutions in the future.”
Dr. Samuelson-Jones has been a consultant for Pfizer, Bayer, Genentech, Frontera, and Cabaletta and serves on the scientific advisory board of GeneVentiv. Dr. d’Oiron has reported relationships with Baxalta/Shire, Bayer, Biomarin, CSL Behring, LFB, NovoNordisk, Octapharma, Pfizer, Roche, and Sobi. Dr. Lassila has been an adviser for Roche (emicizumab) and Biomarin and CSL for gene therapy.
Ultimately, results of a very informal polling of the online audience suggested a strong leaning toward the known benefits of nonfactor therapy, as opposed to as-yet unapproved gene therapy. Although Benjamin Samelson-Jones, MD, PhD, argued for gene therapy, he also saluted the progress made that had enabled such choices.
“Our patients and the field have greatly benefited from this broad spectrum of different therapies and how they’ve been implemented, and it’s a truly exciting time because there will continue to be advancements in both these therapeutic modalities in the next 5-10 years,” said Dr. Samelson-Jones, an assistant professor of pediatrics in the division of hematology at the Children’s Hospital of Philadelphia.
Game changers emerge
Hemophilia A, characterized by a hereditary deficiency in factor VIII disorder, has long involved prophylaxis treatment with procoagulant factor replacement therapy that requires intravenous injection as often as several times a week. This can cause problems with venous access that are particularly burdensome for child patients.
Nonfactor therapy, currently consisting of the approved emicizumab but with more agents in development, provides coagulation without replacement of factor VIII. Importantly, this treatment requires only subcutaneous injection which, after a loading dose period, may be needed weekly or even just once a month.
However, in 2018, at approximately the same time that emicizumab was approved, patients with hemophilia A became eligible to enroll in clinical trials for the far more revolutionary concept of gene therapy, with the chance to become infusion free after just a single infusion.
There are caveats aplenty. Four of the therapies now in phase 3 development are adeno-associated viral vectors that are liver directed, meaning that patients need to be closely followed in the first months post infusion, with regular blood tests and other monitoring.
Notably, once patients receive an infusion, they cannot receive another, because of the buildup of antibodies.
“I think [this is] most important when considering current gene therapy – a patient can only receive it once, based on current technology,” Dr. Samelson-Jones said in an interview.“That means if a patient received gene therapy in 2023, and something better is developed in 2025, they are unlikely to be able to receive it.”
Nevertheless, with favorable phase 3 data reported in March 2022 in the New England Journal of Medicine, the first gene therapy for hemophilia A, valoctocogene roxaparvovec (BioMarin), appears poised for possible regulatory approval very soon.
“I expect this product to be approved in the next year, though I been previously surprised before about delays in this product’s clinical development,” Dr. Samelson-Jones said.
Pros of nonfactor therapy
Arguing on the side of nonfactor therapy in the debate, Roseline d’Oiron, MD, underscored the extent to which nonfactor therapy has dramatically transformed lives.
With intravenous injections, “the burden of the stress and anxiety of the injections is underestimated, even when you don’t have venous access problems,” said Dr. d’Oiron, a clinician investigator at the University Paris XI.
The heavy toll that these therapeutic challenges have had on patients’ lives and identities has been documented in patient advocacy reports, underscoring that “the availability of subcutaneous therapies through the nonfactor therapies for hemophilia A has really been a game changer,” said Dr. d’Oiron, who is also the associate director of the Reference Centre for Hemophilia and Other Congenital Rare Bleeding Disorders, Congenital Platelets Disorders, and von Willebrand Disease at Bicêtre (France) Hospital AP-HP.
She noted that newer therapies in development show the potential to offer longer half-lives, providing “even more improvement with wider intervals between the subcutaneous injections.”
The efficacy of nonfactor therapies also translates to lower rates of joint bleeding, which represent the most common complication in hemophilia, potentially causing acute or chronic pain.
“These therapies allow a life that is much closer to what would be considered a normal life, and especially allowing some physical activities with the prevention of bleeding episodes,” Dr. d’Oiron said. “The drugs have a good safety profile and are completely changing the picture of this disease.”
Dr. d’Oiron noted that, in the real-world clinical setting, there is no debate over nonfactor versus gene therapy. Most prefer to stick with what is already working well for them.
“In my clinical practice, only a very limited number of patients are really willing and considering the switch to gene therapy,” she said. “They feel that the nonfactor therapy is filling their previous unmet needs quite well, and the impression is that we don’t necessarily need look for something different.”
Limitations of nonfactor therapy
Echoing that he has had the same favorable experiences with patients on emicizumab as described by Dr. d’Oiron, Dr. Samelson-Jones, pointed out key caveats that significantly differentiate it from gene therapy, not the least of which is the basic issue of the requirement of injections.
“Even with longer half-lives, approximately monthly injections are still required with nonfactor therapy,” which can – and have – been compromised by any range of societal disruptions, including a pandemic or supply issues.
Furthermore, the mechanism of nonfactor therapies in providing hemostatic regulation outside of normal factor VIII is unregulated, with ‘no easy ‘off’ switch,’ he explained.
“The balance that nonfactor agents provide between pro- and anticoagulant forces is inherently more fragile – more like a knife’s edge, and has resulted in the risk for thrombotic complications in most examples of nonfactor therapies,” he said.
In addition, the therapies have unknown immunogenicity, with an increased risk of the development of antidrug antibodies, called inhibitors, a theoretical complication of nonfactor therapies, if factor VIII is only administered in the setting of bleeds or perioperatively, Dr. Samelson-Jones said.
That being said, “nonfactor agents are not for all patients with hemophilia A in the future – but rather gene therapy is,” he noted.
Normal hemostasis ‘only achievable with gene therapy’
In contrast to nonfactor therapy, just one infusion of gene therapy “ideally offers many years of potentially curative hemostatic protection,” Dr. Samuelson-Jones said. “The ultimate goal, I believe, is to achieve normal hemostasis and health equity, and I contend this goal is only really achievable with gene therapy.”
He noted that, while gene therapies will require initial monitoring, “once the gene therapy recipient is 3 or 12 months out, the monitoring really de-escalates, and the patient is free from all drug delivery or needing to be in close contact with their treatment center.”
Regarding concerns about not being able to receive gene therapy more than once, Dr. Samuelson-Jones said that work is underway to develop alternative viral vectors and nonviral vectors that may overcome those challenges.
Overall, he underscored that challenges are par for the course in the development of any novel therapeutic approach.
For instance, similar challenges were experienced 10 years ago in the development of gene therapy for hemophilia B. However, with advances, “they’ve now been able to achieve long-term sustained levels in the normal ordinary curative range. And I’m optimistic that similar advances may be able to be achieved for factor VIII gene transfer,” he said.
Nonfactor therapies as bridge?
That being said, nonfactor therapies are going to be essential in treating patients until such advances come to fruition, Dr. Samelson-Jones noted.
“I would agree that nonfactor therapies in 2022 have really simplified and improved the convenience of prophylaxis,” he said, “but I would view them as a bridging therapy until gene therapy goes through clinical development and are licensed for all patients with hemophilia.”
While Dr. d’Oiron agreed with that possibility, she countered that, when it comes to crossing over to gene therapy, some very long bridges might be needed.
“I would love to have a therapy that would be both extremely safe and effective and offering a cure and normalization of hemostasis,” she said. “But I’m afraid that the current available gene therapy that might be arriving soon still does no fulfill all of these criteria. I think there are a lot of questions so far.”
Ultimately, Dr. Samelson-Jones conceded that the success of emicizumab has set a high bar in the minds of clinicians and patients alike, which will strongly influence perceptions of any alternative approaches –and of participation in clinical trials.
“I think that, unequivocally, emicizumab has changed the risk-benefit discussion about enrolling in clinical trials, and in gene therapy in particular,” he said. “And I think it also has set the threshold for efficacy – and if a gene therapy product in development can’t achieve bleeding control that is similar to that provided with emicizumab, then that is not a product that is going to be able to continue in clinical development.”
Importantly, both debaters underscored the need for ongoing efforts to make the novel – and therefore costly therapies accessible to all, through organizations including the World Federation of Hemophilia Humanitarian Aid Program.
“It would be my hope that we can then extend all of these great therapies to the majority of undertreated patients with hemophilia around the world,” Dr. Samelson-Jones said. “I think that’s an issue that must be addressed with all of these novel therapies.”
Commenting on these issues, Riitta Lassila, MD, professor of coagulation medicine at the Comprehensive Cancer Center at Helsinki University Hospital, , who moderated the debate, said it has also been her experience that some patients express reluctance to enter the gene therapy trials
“There are two groups of patients, just as in the healthy population as well,” she said in an interview. “Some more ready to take risks and some are very hesitant [regarding] anything new. We do have the saying: If something is not broken, don’t fix it.”
She noted the additional concern that while the therapy has been successful in hemophilia B, factor VIII involves a larger construct and may have limitations with hemophilia A.
Furthermore, “the sustainability of factor VIII production may decrease in a couple of years, and the treatment duration could remain suboptimal,” Dr. Lassila said. “However, hemostasis seems to still [be achieved] with gene therapy, so maybe there will be more efficient solutions in the future.”
Dr. Samuelson-Jones has been a consultant for Pfizer, Bayer, Genentech, Frontera, and Cabaletta and serves on the scientific advisory board of GeneVentiv. Dr. d’Oiron has reported relationships with Baxalta/Shire, Bayer, Biomarin, CSL Behring, LFB, NovoNordisk, Octapharma, Pfizer, Roche, and Sobi. Dr. Lassila has been an adviser for Roche (emicizumab) and Biomarin and CSL for gene therapy.
Ultimately, results of a very informal polling of the online audience suggested a strong leaning toward the known benefits of nonfactor therapy, as opposed to as-yet unapproved gene therapy. Although Benjamin Samelson-Jones, MD, PhD, argued for gene therapy, he also saluted the progress made that had enabled such choices.
“Our patients and the field have greatly benefited from this broad spectrum of different therapies and how they’ve been implemented, and it’s a truly exciting time because there will continue to be advancements in both these therapeutic modalities in the next 5-10 years,” said Dr. Samelson-Jones, an assistant professor of pediatrics in the division of hematology at the Children’s Hospital of Philadelphia.
Game changers emerge
Hemophilia A, characterized by a hereditary deficiency in factor VIII disorder, has long involved prophylaxis treatment with procoagulant factor replacement therapy that requires intravenous injection as often as several times a week. This can cause problems with venous access that are particularly burdensome for child patients.
Nonfactor therapy, currently consisting of the approved emicizumab but with more agents in development, provides coagulation without replacement of factor VIII. Importantly, this treatment requires only subcutaneous injection which, after a loading dose period, may be needed weekly or even just once a month.
However, in 2018, at approximately the same time that emicizumab was approved, patients with hemophilia A became eligible to enroll in clinical trials for the far more revolutionary concept of gene therapy, with the chance to become infusion free after just a single infusion.
There are caveats aplenty. Four of the therapies now in phase 3 development are adeno-associated viral vectors that are liver directed, meaning that patients need to be closely followed in the first months post infusion, with regular blood tests and other monitoring.
Notably, once patients receive an infusion, they cannot receive another, because of the buildup of antibodies.
“I think [this is] most important when considering current gene therapy – a patient can only receive it once, based on current technology,” Dr. Samelson-Jones said in an interview.“That means if a patient received gene therapy in 2023, and something better is developed in 2025, they are unlikely to be able to receive it.”
Nevertheless, with favorable phase 3 data reported in March 2022 in the New England Journal of Medicine, the first gene therapy for hemophilia A, valoctocogene roxaparvovec (BioMarin), appears poised for possible regulatory approval very soon.
“I expect this product to be approved in the next year, though I been previously surprised before about delays in this product’s clinical development,” Dr. Samelson-Jones said.
Pros of nonfactor therapy
Arguing on the side of nonfactor therapy in the debate, Roseline d’Oiron, MD, underscored the extent to which nonfactor therapy has dramatically transformed lives.
With intravenous injections, “the burden of the stress and anxiety of the injections is underestimated, even when you don’t have venous access problems,” said Dr. d’Oiron, a clinician investigator at the University Paris XI.
The heavy toll that these therapeutic challenges have had on patients’ lives and identities has been documented in patient advocacy reports, underscoring that “the availability of subcutaneous therapies through the nonfactor therapies for hemophilia A has really been a game changer,” said Dr. d’Oiron, who is also the associate director of the Reference Centre for Hemophilia and Other Congenital Rare Bleeding Disorders, Congenital Platelets Disorders, and von Willebrand Disease at Bicêtre (France) Hospital AP-HP.
She noted that newer therapies in development show the potential to offer longer half-lives, providing “even more improvement with wider intervals between the subcutaneous injections.”
The efficacy of nonfactor therapies also translates to lower rates of joint bleeding, which represent the most common complication in hemophilia, potentially causing acute or chronic pain.
“These therapies allow a life that is much closer to what would be considered a normal life, and especially allowing some physical activities with the prevention of bleeding episodes,” Dr. d’Oiron said. “The drugs have a good safety profile and are completely changing the picture of this disease.”
Dr. d’Oiron noted that, in the real-world clinical setting, there is no debate over nonfactor versus gene therapy. Most prefer to stick with what is already working well for them.
“In my clinical practice, only a very limited number of patients are really willing and considering the switch to gene therapy,” she said. “They feel that the nonfactor therapy is filling their previous unmet needs quite well, and the impression is that we don’t necessarily need look for something different.”
Limitations of nonfactor therapy
Echoing that he has had the same favorable experiences with patients on emicizumab as described by Dr. d’Oiron, Dr. Samelson-Jones, pointed out key caveats that significantly differentiate it from gene therapy, not the least of which is the basic issue of the requirement of injections.
“Even with longer half-lives, approximately monthly injections are still required with nonfactor therapy,” which can – and have – been compromised by any range of societal disruptions, including a pandemic or supply issues.
Furthermore, the mechanism of nonfactor therapies in providing hemostatic regulation outside of normal factor VIII is unregulated, with ‘no easy ‘off’ switch,’ he explained.
“The balance that nonfactor agents provide between pro- and anticoagulant forces is inherently more fragile – more like a knife’s edge, and has resulted in the risk for thrombotic complications in most examples of nonfactor therapies,” he said.
In addition, the therapies have unknown immunogenicity, with an increased risk of the development of antidrug antibodies, called inhibitors, a theoretical complication of nonfactor therapies, if factor VIII is only administered in the setting of bleeds or perioperatively, Dr. Samelson-Jones said.
That being said, “nonfactor agents are not for all patients with hemophilia A in the future – but rather gene therapy is,” he noted.
Normal hemostasis ‘only achievable with gene therapy’
In contrast to nonfactor therapy, just one infusion of gene therapy “ideally offers many years of potentially curative hemostatic protection,” Dr. Samuelson-Jones said. “The ultimate goal, I believe, is to achieve normal hemostasis and health equity, and I contend this goal is only really achievable with gene therapy.”
He noted that, while gene therapies will require initial monitoring, “once the gene therapy recipient is 3 or 12 months out, the monitoring really de-escalates, and the patient is free from all drug delivery or needing to be in close contact with their treatment center.”
Regarding concerns about not being able to receive gene therapy more than once, Dr. Samuelson-Jones said that work is underway to develop alternative viral vectors and nonviral vectors that may overcome those challenges.
Overall, he underscored that challenges are par for the course in the development of any novel therapeutic approach.
For instance, similar challenges were experienced 10 years ago in the development of gene therapy for hemophilia B. However, with advances, “they’ve now been able to achieve long-term sustained levels in the normal ordinary curative range. And I’m optimistic that similar advances may be able to be achieved for factor VIII gene transfer,” he said.
Nonfactor therapies as bridge?
That being said, nonfactor therapies are going to be essential in treating patients until such advances come to fruition, Dr. Samelson-Jones noted.
“I would agree that nonfactor therapies in 2022 have really simplified and improved the convenience of prophylaxis,” he said, “but I would view them as a bridging therapy until gene therapy goes through clinical development and are licensed for all patients with hemophilia.”
While Dr. d’Oiron agreed with that possibility, she countered that, when it comes to crossing over to gene therapy, some very long bridges might be needed.
“I would love to have a therapy that would be both extremely safe and effective and offering a cure and normalization of hemostasis,” she said. “But I’m afraid that the current available gene therapy that might be arriving soon still does no fulfill all of these criteria. I think there are a lot of questions so far.”
Ultimately, Dr. Samelson-Jones conceded that the success of emicizumab has set a high bar in the minds of clinicians and patients alike, which will strongly influence perceptions of any alternative approaches –and of participation in clinical trials.
“I think that, unequivocally, emicizumab has changed the risk-benefit discussion about enrolling in clinical trials, and in gene therapy in particular,” he said. “And I think it also has set the threshold for efficacy – and if a gene therapy product in development can’t achieve bleeding control that is similar to that provided with emicizumab, then that is not a product that is going to be able to continue in clinical development.”
Importantly, both debaters underscored the need for ongoing efforts to make the novel – and therefore costly therapies accessible to all, through organizations including the World Federation of Hemophilia Humanitarian Aid Program.
“It would be my hope that we can then extend all of these great therapies to the majority of undertreated patients with hemophilia around the world,” Dr. Samelson-Jones said. “I think that’s an issue that must be addressed with all of these novel therapies.”
Commenting on these issues, Riitta Lassila, MD, professor of coagulation medicine at the Comprehensive Cancer Center at Helsinki University Hospital, , who moderated the debate, said it has also been her experience that some patients express reluctance to enter the gene therapy trials
“There are two groups of patients, just as in the healthy population as well,” she said in an interview. “Some more ready to take risks and some are very hesitant [regarding] anything new. We do have the saying: If something is not broken, don’t fix it.”
She noted the additional concern that while the therapy has been successful in hemophilia B, factor VIII involves a larger construct and may have limitations with hemophilia A.
Furthermore, “the sustainability of factor VIII production may decrease in a couple of years, and the treatment duration could remain suboptimal,” Dr. Lassila said. “However, hemostasis seems to still [be achieved] with gene therapy, so maybe there will be more efficient solutions in the future.”
Dr. Samuelson-Jones has been a consultant for Pfizer, Bayer, Genentech, Frontera, and Cabaletta and serves on the scientific advisory board of GeneVentiv. Dr. d’Oiron has reported relationships with Baxalta/Shire, Bayer, Biomarin, CSL Behring, LFB, NovoNordisk, Octapharma, Pfizer, Roche, and Sobi. Dr. Lassila has been an adviser for Roche (emicizumab) and Biomarin and CSL for gene therapy.
FROM EHA 2022
Experts opine on hemophilia treatments
, according to a recent report in The Journal of Medicine in Life.
To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.
“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.
The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.
They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.
About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.
However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.
“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.
There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.
The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.
“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.
In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.
For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.
Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.
Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.
The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.
, according to a recent report in The Journal of Medicine in Life.
To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.
“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.
The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.
They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.
About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.
However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.
“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.
There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.
The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.
“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.
In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.
For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.
Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.
Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.
The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.
, according to a recent report in The Journal of Medicine in Life.
To get there, the World Federation of Hemophilia (WFH) has recognized that physicians need to aim for higher trough levels so patients can lead as normal a life as possible, but there’s debate about which levels are ideal.
“There is increasing recognition and evidence from the literature that factor trough levels of 1%-3% are insufficient to prevent bleeds in all patients with hemophilia. It has also been suggested that maintaining higher factor levels (above 10%) may be optimal to prevent subclinical bleeding and the gradual progression of joint disease over a lifespan in very active patients,” according to the report.
The paper was a summary of expert opinion on the issue and a range of other current and future challenges in hemophilia care. Switzerland-based Sobi surveyed nine hemophilia experts in central Europe for their insights, then convened an advisory panel to flesh out their responses.
They were asked for their thoughts on the efficacy of factor versus non-factor replacement therapy when aiming for a 3%-5% target trough for hemophilia A prophylaxis.
About half said non-factor therapy was more effective, while the other half favored factor therapy because it has similar efficacy and allows the tailoring of treatment to individual pharmacokinetic data, physical activity, and the condition of the musculoskeletal system.
However, “if the new treatment aim for [prophylaxis] is to increase the trough level, existing and future prophylactic regimens are likely to require adjustment. Maintaining such high trough levels in some patients may lead to the re-shortening of longer treatment intervals and, consequently, an increase of previously reduced factor consumption, which has been an important benefit of [extended half-life] products,” the report noted.
“This creates space for next-generation FVIII replacement therapy,” such as Sobi’s efanesoctocog alfa, which has been granted fast-track designation in the United States for hemophilia treatment, the report notes.
There was also a split in opinion on whether factor therapy offered similar or improved efficacy, compared with non-factor therapy when prophylaxis is intensified to aim for a 10% trough in very active patients. Factor prophylaxis “may be preferable for active hemophilia A” because of the greater personalization, it said.
The experts noted that trough levels are just one aspect of patient care; the overall aim is a better quality of life. The panel was asked about how quality of life could be enhanced in the future. More than half said that the move towards personalized treatment is key, including greater use of telemedicine applications such as Sobi’s florio HAEMO and Takeda’s MyPKFit.
“In addition, most of the experts agreed that novel therapies such as the new class of FVIII replacement therapy, efanesoctocog alfa (BIVV001), would become another mainstream therapy due to its potential to achieve personalized, extended protection against all bleeding types in patients with severe hemophilia A,” the report said.
In the meantime, the advent of extended half-life products and novel non-factor therapies such as emicizumab; subcutaneous siRNA prophylactic therapies such as fitusiran; and anti-tissue factor pathway inhibitors such as marstacimab – each with different mechanisms of action – has led to new challenges in laboratory monitoring.
For more personalized treatment to happen, “it will be necessary for specialized clinical laboratories to be fully equipped with the required equipment, product-specific reagents, and expertise to perform appropriate assays and monitor levels of coagulation activity,” the report noted.
Thrombin generation assays to measure the dynamics of blood coagulation are promising. “There’s significant potential for monitoring the efficacy” of prophylaxis across various established and novel hemophilia treatments, but the approach “is still in its infancy,” the report noted.
Overall, “new and emerging therapies such as novel [extended half-life] factor concentrates and non-factor treatments will likely reshape hemophilia care within the next decade, providing more efficacious and convenient management options and possibly curative therapies,” it said.
The work was funded by Sobi. Most of the panelists disclosed speaker/advisor fees and/or research funding from the company, as well as many others.
FROM The JOURNAL OF MEDICINE AND LIFE
Venetoclax combos prolong progression-free CLL survival
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding the Bruton tyrosine kinase inhibitor ibrutinib to the two-drug combination pushed the 3-year PFS even higher, but the risk of severe adverse events may outweigh the benefits of the triple combination for some higher-risk patients.
“Time-limited targeted therapy with venetoclax plus obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy with respect to progression-free survival,” said first author Barbara Eichhorst, MD, of the University of Cologne (Germany).
However, given higher rates of infection and other adverse events observed when adding ibrutinib, “I would say, based on this data, not to use the triple combination in clinical practice,” Dr. Eichhorst cautioned.
Dr. Eichhorst presented these late-breaking results at the European Hematology Association annual congress.
For patients considered unfit for chemoimmunotherapy, the fixed-duration therapy of venetoclax plus obinutuzumab has become standard treatment for CLL. For those deemed fit to withstand chemoimmunotherapy, this option remains the standard of care.
However, no studies have compared the targeted combination with chemoimmunotherapy for fit patients with CLL.
Dr. Eichhorst and colleagues conducted the GAIA/CLL13 trial to determine how the two- or three-drug targeted combinations stack up against standard chemoimmunotherapy for fit patients.
In the phase 3 study, 920 treatment-naive, fit patients with CLL in which there were no TP53 aberrations were randomly assigned to one of four treatment groups that each had 230 patients – standard chemoimmunotherapy or one of three time-limited venetoclax arms.
The regimen for the chemoimmunotherapy group included fludarabine, cyclophosphamide, and rituximab for those aged 65 and younger, and bendamustine and rituximab for those over 65. The patients who received venetoclax were divided into groups that received either venetoclax plus rituximab, venetoclax plus obinutuzumab, or triple therapy of venetoclax, obinutuzumab, and ibrutinib.
The median age was 61, and follow-up was just over 3 years (38.8 months). Nearly 40% of patients were in advanced Binet stages, and more than half (56%) were of unmutated immunoglobulin heavy chain gene (IgVH) status, which is associated with worse outcomes in CLL.
Compared with chemotherapy, the two-drug combination demonstrated significantly better PFS (hazard ratio, 0.32; P < .000001), as did the triple therapy (HR, 0.42; P < .001), though the venetoclax-rituximab combination did not (HR, 0.79; P = .183).
The 3-year PFS rates were highest in the triple-therapy group (90.5%), followed by the venetoclax and obinutuzumab group (87.7%). The chemoimmunotherapy (75.5%) and venetoclax plus rituximab groups (80.8%) had the lowest 3-year PFS rates.
Overall, 3-year PFS rates for patients with unmutated IgVH were slightly lower, compared with those who had mutated IgVH.
The best PFS rate was among patients who received the 3-drug combination, although one interesting caveat emerged among the under-65 subset of patients in the mutated IgVH group: the chemotherapy arm achieved a slightly better PFS rate (95%) compared with the triple-therapy arm (93.6%).
Notably, overall survival was similar among all groups; about 96% of patients were alive at 3 years.
Several adverse events were more pronounced in the triple-therapy group. The highest rate of grade 3-4 infections was among those who received ibrutinib (22.1% vs. 20.4% for chemotherapy, 11.4% for venetoclax/rituximab, and 14.9% for venetoclax/obinutuzumab). The triple-therapy group also had the highest rate of hypertension (5.6% vs. 1.4% for chemotherapy, 2.1% for venetoclax/rituximab, and 1.8% for venetoclax/obinutuzumab).
Rates of febrile neutropenia and secondary primary malignancies, however, were highest in the chemoimmunotherapy group. More than 11% of patients in the chemoimmunotherapy group had febrile neutropenia, compared with 7.8% of those who received triple therapy, 4.2% in the venetoclax/rituximab group, and 3.1% of those who received venetoclax/obinutuzumab. Almost half of patients in the chemoimmunotherapy group had secondary primary malignancies versus fewer than 30% in the other arms.
EHA President-Elect António Almeida, MD, noted that the research sheds important light on evolving treatment options for CLL.
“The first is that the triple combination appears better than the double combinations, and I think that’s an important message because of longer treatment-free remission and progression-free remissions,” Dr. Almeida, of the Hospital da Luz, Lisbon, said in an interview.
The second important message: Given the time-limited administration of the venetoclax combinations, the data show that “we can stop ibrutinib and that is safe,” he added. “That’s quite important.”
Third, the findings can help guide treatment choices. “We’ve already had an indication that obinutuzumab is better than rituximab in the CLL setting, but this again solidifies that notion,” Dr. Almeida added.
Dr. Eichhorst has relationships with Janssen, Gilead, F. Hoffmann–La Roche, AbbVie, BeiGene, AstraZeneca, MSD, Adaptive Biotechnologies, and Hexal. Dr. Almeida disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EHA 2022
Microbiome’s new happy place: The beer gut
Your gut microbiome will thank you later
A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?
In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.
Beer? Yes. Beer.
We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?
In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.
So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
We’ve lost our minds, but at least we know how fast they’re going
The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”
When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.
To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.
That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.
The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
Missing links: A real fish story
Dear LOTME:
Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?
Restless in Roswell
Dear Restless:
The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.
For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?
The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.
“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.
In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.
So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
Can you lend me an ear?
If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?
Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?
“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.
And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”
The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!
Your gut microbiome will thank you later
A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?
In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.
Beer? Yes. Beer.
We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?
In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.
So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
We’ve lost our minds, but at least we know how fast they’re going
The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”
When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.
To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.
That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.
The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
Missing links: A real fish story
Dear LOTME:
Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?
Restless in Roswell
Dear Restless:
The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.
For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?
The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.
“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.
In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.
So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
Can you lend me an ear?
If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?
Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?
“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.
And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”
The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!
Your gut microbiome will thank you later
A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?
In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.
Beer? Yes. Beer.
We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?
In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.
So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
We’ve lost our minds, but at least we know how fast they’re going
The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”
When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.
To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.
That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.
The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
Missing links: A real fish story
Dear LOTME:
Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?
Restless in Roswell
Dear Restless:
The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.
For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?
The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.
“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.
In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.
So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
Can you lend me an ear?
If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?
Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?
“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.
And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”
The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!
Momelotinib hits the mark for deadly bone marrow cancer
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
FROM ASCO 2022
Severe COVID-19 and blood cancer: Plasma therapy may help
, new research shows.
The study demonstrated that “plasma from convalescent or vaccinated individuals shortens the time to improvement in hematological and solid cancer patients with severe COVID-19” and “prolongs overall survival,” said study coauthor Maike Janssen, MD, of the department of internal medicine at Heidelberg (Germany) University Hospital.
Dr. Janssen presented the study findings at the annual congress of the European Hematology Association held in Vienna.
Although people with COVID-19 do not appear to benefit from treatment with convalescent plasma, some data indicate that certain patients who cannot mount a strong immune response to SARS-CoV-2 infection may benefit.
In this recent multicenter study, 134 patients with confirmed COVID-19 whose oxygen saturation was 94% or lower were randomly assigned to undergo treatment with convalescent or vaccinated SARS-CoV-2 plasma (n = 68) or to receive standard of care (n = 66). Patients fell into four clinical groups: those with a hematologic malignancy or who had undergone active cancer therapy for any cancer within the past 24 months; those with chronic immunosuppression; those between the ages of 50 and 75 with lymphopenia and/or elevated D-dimer levels; and those older than 75 years.
The convalescent or vaccinated SARS-CoV-2 plasma was administered in two bags (238-337 mL plasma each) from different donors on days 1 and 2. Only plasma from donors with high levels of neutralizing activity (titers above 1:80) were included. The primary endpoint was time to improvement by 2 points on a 7-point scale or discharge from the hospital. The secondary endpoint was improvement in overall survival.
The authors found that overall, patients in the plasma group demonstrated a shorter time to improvement – median of 12.5 days, vs. 18 days – but the difference was not significant (P = .29).
However, for the subgroup of 56 patients with hematologic/solid cancers, the time to improvement was significantly shorter: 13 days vs. 31 days (hazard ratio [HR], 2.5; P = .003).
Similarly, plasma therapy did not improve overall survival in the study population overall – there were 12 deaths in the plasma group over 80 days, vs. 15 in the control group (P = .80). Patients in the hematologic/solid cancer subgroup who received plasma therapy did demonstrate significantly better overall survival (HR, 0.28; P = .042).
No similar significant differences in time to improvement or overall survival were observed in the other three groups. “We found that plasma did not improve outcomes in immune-competent patients with other risk factors and/or older age,” Dr. Janssen said.
Although study enrollment ended when the Omicron variant began surging, Dr. Janssen noted that plasma from Omicron patients may also be of benefit to those with hematologic cancers.
“We have treated some patients in individual cases using plasma from Omicron patients who were already vaccinated or with breakthrough infections, and we did see benefits in those cases,” she noted.
The study was funded by the Federal Ministry of Education and Research, Germany. Dr. Janssen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
The study demonstrated that “plasma from convalescent or vaccinated individuals shortens the time to improvement in hematological and solid cancer patients with severe COVID-19” and “prolongs overall survival,” said study coauthor Maike Janssen, MD, of the department of internal medicine at Heidelberg (Germany) University Hospital.
Dr. Janssen presented the study findings at the annual congress of the European Hematology Association held in Vienna.
Although people with COVID-19 do not appear to benefit from treatment with convalescent plasma, some data indicate that certain patients who cannot mount a strong immune response to SARS-CoV-2 infection may benefit.
In this recent multicenter study, 134 patients with confirmed COVID-19 whose oxygen saturation was 94% or lower were randomly assigned to undergo treatment with convalescent or vaccinated SARS-CoV-2 plasma (n = 68) or to receive standard of care (n = 66). Patients fell into four clinical groups: those with a hematologic malignancy or who had undergone active cancer therapy for any cancer within the past 24 months; those with chronic immunosuppression; those between the ages of 50 and 75 with lymphopenia and/or elevated D-dimer levels; and those older than 75 years.
The convalescent or vaccinated SARS-CoV-2 plasma was administered in two bags (238-337 mL plasma each) from different donors on days 1 and 2. Only plasma from donors with high levels of neutralizing activity (titers above 1:80) were included. The primary endpoint was time to improvement by 2 points on a 7-point scale or discharge from the hospital. The secondary endpoint was improvement in overall survival.
The authors found that overall, patients in the plasma group demonstrated a shorter time to improvement – median of 12.5 days, vs. 18 days – but the difference was not significant (P = .29).
However, for the subgroup of 56 patients with hematologic/solid cancers, the time to improvement was significantly shorter: 13 days vs. 31 days (hazard ratio [HR], 2.5; P = .003).
Similarly, plasma therapy did not improve overall survival in the study population overall – there were 12 deaths in the plasma group over 80 days, vs. 15 in the control group (P = .80). Patients in the hematologic/solid cancer subgroup who received plasma therapy did demonstrate significantly better overall survival (HR, 0.28; P = .042).
No similar significant differences in time to improvement or overall survival were observed in the other three groups. “We found that plasma did not improve outcomes in immune-competent patients with other risk factors and/or older age,” Dr. Janssen said.
Although study enrollment ended when the Omicron variant began surging, Dr. Janssen noted that plasma from Omicron patients may also be of benefit to those with hematologic cancers.
“We have treated some patients in individual cases using plasma from Omicron patients who were already vaccinated or with breakthrough infections, and we did see benefits in those cases,” she noted.
The study was funded by the Federal Ministry of Education and Research, Germany. Dr. Janssen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
The study demonstrated that “plasma from convalescent or vaccinated individuals shortens the time to improvement in hematological and solid cancer patients with severe COVID-19” and “prolongs overall survival,” said study coauthor Maike Janssen, MD, of the department of internal medicine at Heidelberg (Germany) University Hospital.
Dr. Janssen presented the study findings at the annual congress of the European Hematology Association held in Vienna.
Although people with COVID-19 do not appear to benefit from treatment with convalescent plasma, some data indicate that certain patients who cannot mount a strong immune response to SARS-CoV-2 infection may benefit.
In this recent multicenter study, 134 patients with confirmed COVID-19 whose oxygen saturation was 94% or lower were randomly assigned to undergo treatment with convalescent or vaccinated SARS-CoV-2 plasma (n = 68) or to receive standard of care (n = 66). Patients fell into four clinical groups: those with a hematologic malignancy or who had undergone active cancer therapy for any cancer within the past 24 months; those with chronic immunosuppression; those between the ages of 50 and 75 with lymphopenia and/or elevated D-dimer levels; and those older than 75 years.
The convalescent or vaccinated SARS-CoV-2 plasma was administered in two bags (238-337 mL plasma each) from different donors on days 1 and 2. Only plasma from donors with high levels of neutralizing activity (titers above 1:80) were included. The primary endpoint was time to improvement by 2 points on a 7-point scale or discharge from the hospital. The secondary endpoint was improvement in overall survival.
The authors found that overall, patients in the plasma group demonstrated a shorter time to improvement – median of 12.5 days, vs. 18 days – but the difference was not significant (P = .29).
However, for the subgroup of 56 patients with hematologic/solid cancers, the time to improvement was significantly shorter: 13 days vs. 31 days (hazard ratio [HR], 2.5; P = .003).
Similarly, plasma therapy did not improve overall survival in the study population overall – there were 12 deaths in the plasma group over 80 days, vs. 15 in the control group (P = .80). Patients in the hematologic/solid cancer subgroup who received plasma therapy did demonstrate significantly better overall survival (HR, 0.28; P = .042).
No similar significant differences in time to improvement or overall survival were observed in the other three groups. “We found that plasma did not improve outcomes in immune-competent patients with other risk factors and/or older age,” Dr. Janssen said.
Although study enrollment ended when the Omicron variant began surging, Dr. Janssen noted that plasma from Omicron patients may also be of benefit to those with hematologic cancers.
“We have treated some patients in individual cases using plasma from Omicron patients who were already vaccinated or with breakthrough infections, and we did see benefits in those cases,” she noted.
The study was funded by the Federal Ministry of Education and Research, Germany. Dr. Janssen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EHA 2022
‘My malpractice insurance doubled!’ Why, when fewer patients are suing?
Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.
In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.
“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”
Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.
“If claims are going down, I don’t understand why premium payments are going up,” she said.
Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.
Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.
Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.
According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.
The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
Cases plummet during pandemic
During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.
“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”
The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.
“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”
In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.
But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.
“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
High-dollar verdicts pave expensive path
The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.
“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”
In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.
Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.
“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”
High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.
“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
What does 2022 have in store?
Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.
Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.
Such delayed claims may end up costing more because of social inflation, said Mr. Burns.
“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”
Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.
“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”
As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.
“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”
For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.
“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”
A version of this article first appeared on Medscape.com.
Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.
In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.
“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”
Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.
“If claims are going down, I don’t understand why premium payments are going up,” she said.
Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.
Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.
Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.
According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.
The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
Cases plummet during pandemic
During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.
“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”
The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.
“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”
In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.
But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.
“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
High-dollar verdicts pave expensive path
The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.
“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”
In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.
Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.
“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”
High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.
“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
What does 2022 have in store?
Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.
Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.
Such delayed claims may end up costing more because of social inflation, said Mr. Burns.
“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”
Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.
“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”
As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.
“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”
For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.
“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”
A version of this article first appeared on Medscape.com.
Angela Intili, MD, an ob.gyn., was used to seeing her medical malpractice insurance premium rise slightly every couple of years. But she was shocked by the drastic rise she recently experienced.
In the last 2 years, Dr. Intili’s premiums shot from $60,000 to $130,000, she said.
“After 30 years of practice, this is the first time I’ve asked myself if I can even afford to continue practicing obstetrics and gynecology,” said Dr. Intili, 62, of Joliet, Ill. “It’s gotten very difficult to make ends meet as far as overhead because of the liability costs. I still love what I’m doing but I don’t know if I can afford to do it anymore.”
Even more frustrating for Dr. Intili was learning that claims in Illinois have sharply declined. From 2016 to 2020, tort filings in Illinois decreased by 43%, according to a state report.
“If claims are going down, I don’t understand why premium payments are going up,” she said.
Physicians across the country are experiencing a similar paradox. Claims are down, yet premiums are rising.
Medscape’s Malpractice Report 2021 found that 42% of primary care physicians were sued in 2020 through mid-2021, down from 52% in 2019. Fifty-six percent of specialists were sued in 2020 through mid-2021 compared with 62% in 2019, the report found. The pandemic was undoubtedly behind the decrease in suits, according to legal experts.
Yet, physicians paid higher premiums in 2021 and are on track for increases again in 2022, according to data and analysts.
According to Conning, direct premiums written for physicians increased 7.0% in 2021 (from $5.01 billion to $5.36 billion). Conning, an investment management firm that serves the insurance industry, analyzes annual financial reports filed by insurers to state insurance departments. The Medical Liability Monitor’s 2021 report found that premiums for internists, surgeons, and ob.gyns. in states without Patient Compensation Funds rose by an average of 2% in 2021.
The disparities raise questions about why physicians are paying higher premiums when having fewer claims is likely saving insurers’ money. Shouldn’t physicians’ rates reflect the reduction in claims?
Cases plummet during pandemic
During the pandemic, the volume of new medical malpractice claims dwindled to nearly nothing, said Michael Matray, editor of the Medical Liability Monitor, a national publication that analyzes medical liability insurance premiums.
“The court system closed for a while,” he said. “No elective procedures were being done in 2020 and the early parts of 2021. If you have no treatment, you have no malpractice, so of course, claims frequency tumbled down to a trickle.”
The number of large awards also decreased during the pandemic, noted Bill Burns, a director of insurance research at Conning.
“For claims that were already in the system, many of them could not be resolved because of the court closures, inability to take statements and depositions, etc.,” he said. “This resulted in a drop in verdicts.”
In 2021, there were 16 medical malpractice verdicts of $10 million or more in the United States, according to TransRe, an international reinsurance company that tracks large verdicts. In 2020, there were six verdicts of $10 million or more, TransRe research found. This is down from 52 verdicts of $10 million or more in 2019 and 46 verdicts of $10 million or more in 2018.
But although the pandemic lowered claims and decreased the number of payouts, one important aspect was untouched by the COVID era, said Richard E. Anderson, MD, chairman and CEO for The Doctors Company, a national medical liability insurer, and TDC Group.
“It’s a fair question: If claims are down, why are premiums continuing to go up?” Dr. Anderson said. “The answer is severity.”
High-dollar verdicts pave expensive path
The upward trend in severity has continued for about 6 years and has not slowed, Dr. Anderson said. Severity refers to high-dollar verdicts and settlements.
“We’re seeing record-high verdicts all over the country,” he said. “We used to have maps that showed the top 10 medical malpractice verdicts or awards, and they would be clustered where you’d expect them to be, New York, Florida, Illinois, and so forth. Now, if you look at those top 10 verdicts, they could be anywhere in the country.”
In Minnesota for instance, a jury awarded a record $111 million in damages to a college student in May after finding a hospital and an orthopedic surgeon negligent in treating his broken leg. In April, a Kansas City jury awarded a family $25 million after finding that an ob.gyn. and hospital failed to properly treat a mother in labor, causing brain damage to her infant.
Such record payouts factor into premium costs, said Ned Rand Jr., CEO for ProAssurance, a national medical liability insurer. Though only a minority of claims reach that level, when a high award occurs, it puts pressure on the ultimate cost to resolve claims, he said. The frequency of claims filed is also expected to soon rebound, he noted.
“As we price the product sitting here today, we have to factor both of those in,” Mr. Rand said. “That’s why we, as an industry, continue to see, by and large, rates going up. And we fell behind. Some of this severity, in particular, as an industry, we weren’t pricing fully for, so we’ve been playing catch-up.”
High-dollar awards – also called nuclear verdicts – set the arena for future settlements in similar cases, Dr. Anderson added.
“If it was an orthopedic case for instance, and there was a similar injury in another case, that’s the trial lawyers’ starting point for the award,” he said. “Now, they’re not going to get it, but it distorts the negotiations. As we have more and more nuclear verdicts, it becomes harder to settle claims for reasonable amounts.”
What does 2022 have in store?
Analysts say the backlog of malpractice claims in the court system could prove calamitous for premiums and the liability landscape.
Courts are slogging through the pileup caused by the pandemic, but it’s estimated that there is still about a one-third larger case backlog than normal, according to Mr. Matray.
Such delayed claims may end up costing more because of social inflation, said Mr. Burns.
“People look at the world differently than they did 2 years ago,” he said. “A jury may have awarded $5 million for a claim a few years ago. But then the pandemic hits, and we have the George Floyd incident, and we have people out of work and a shortage in baby formula. Yet, companies are still making a lot of money and many insurance companies are turning record profits. Today, that jury may look at a sympathetic malpractice victim and award $10 million for the same claim.”
Concerns also exist about a potential surge of new malpractice claims. Mr. Rand compares the possible wave to a large bubble.
“I liken it to a cartoon, when one character grabs the hose and a big bubble forms as the water builds up,” he said. “Then the character releases, and water comes flooding out. As an industry, we wait, wondering: Is there going to be this flood of claims as the court systems reopen and the statute of limitations approach around some of these claims? That’s an ongoing concern.”
As for impending premiums, physicians can expect rises in 2022 and again in 2023, according to Chris Wojciechowski, a partner at TigerRisk Partners, a reinsurance broker.
“In general, there is a lot of uncertainty around the state of the economy, the tort environment, litigation post COVID, and overall volatility across the capital markets,” he said. “Furthermore, thanks to social and financial inflation, the potential for very severe verdicts has increased dramatically, and as courthouses reopen, the trends are not looking favorable. While many of the physician carriers have strong balance sheets, they can’t lose money on an underwriting basis forever.”
For Dr. Intili, the Illinois ob.gyn., news of another impending increase in 2022 is distressing. She expects another 10%-20% rise in 2022, she said. If she were younger and earlier in her career, she might’ve considered moving, she said, but her family lives in Illinois and she cares for her older parents.
“I’m not ready to retire,” Dr. Intili said. “I’m looking into options, possibly becoming a hospitalist or doing locum tenens work. I’ve been a solo practitioner for 27 years and I love the autonomy. But these high premiums are making it almost impossible to continue.”
A version of this article first appeared on Medscape.com.
Novel gene therapy offers hope for some lymphomas
Not all patients with relapsed or refractory large B cell lymphoma (r/r LBCL) are candidates for high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT), and options for second-line therapies for this population are limited, said Dr. Alison Sehgal of the University of Pittsburgh Medical Center in her presentation of the findings.
Lisocabtagene maraleucel (liso-cel) is a CD19-directed CAR T-cell product. In a previous phase 3 randomized trial (the TRANSFORM study), lisocabtagene showed superiority over salvage chemotherapy for LBCL patients who were fit candidates for stem cell transplant, but its use in older, frail patients who are not transplant candidates remains uncertain, wrote Dr. Sehgal and colleagues in their poster at the meeting.
In the study, the researchers identified 74 patients with r/r LBCL. Of these, 61 were treated with liso-cel. The patients ranged in age from 53 to 84 years, with a median age of 74 years, 61% were male, and 89% were white. Approximately half were refractory and half were relapsed.
For the therapy, patients underwent lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by an infusion of liso-cel at a target dose of 100 x 106 CAR+ T cells; all patients had at least 6 months of follow-up from their first response.
The primary endpoint of overall response rate occurred in 80% of the patients, and clinically meaningful complete response occurred in 54% over a median follow-up of 12.3 months.
“Clinically meaningful CRs were observed across all subgroups,” Dr. Sehgal said in her presentation.
The response lasted a median of 21.7 months, and the median follow-up for duration of response was 15.5 months. The median overall survival was not reached, but the median progression-free survival was 9.0 months, with a median follow-up period of 13.0 months.
Responses occurred across all prespecified subgroups, with no significant differences in either safety or efficacy based on hematopoietic cell transplantation–specific comorbidity index (HCT-CI) scores.
“Despite the advanced age and comorbidities of the population, the safety profile was consistent with previous reports,” and no new or increased safety signals appeared, Dr. Sehgal said.
The most common treatment-emergent adverse events of grade 3 or higher were neutropenia (48%), leukopenia (21%), thrombocytopenia (20%), and anemia (11%). Cytokine-release syndrome (CRS) occurred in 23 patients (38%); of these, 1 patient was grade 3 and none were grades 4 or 5.
Approximately one-third of the patients (31%) experienced neurological events during the study; three cases were grade 3, none were grades 4 or 5. Patients with CRS or NE were treated with tocilizumab (10%), corticosteroids (3%), or both (20%). Treatment-emergent adverse events of grade 3 or higher occurred in 79% of patients overall, including grade 5 events in two patients because of COVID-19.
The study findings were limited by the small sample size and lack of controls. However, the results support the potential use of liso-cel as a second-line therapy for r/r LBCL patients who are not candidates for HSCT, Dr. Sehgal concluded.
Addressing an ongoing unmet need
In an interview, study coauthor Dr. Leo I. Gordon of Northwestern University, Chicago, observed, “Patients with relapsed or refractory large B-cell lymphoma who are not considered candidates for stem cell transplant following first-line treatment, based on age, comorbidities, health status, or other prognostic factors, have more difficult-to-treat disease, poor prognosis, and more limited treatment options.”
Dr. Gordon noted that the PILOT study is the only trial to evaluate a CAR T-cell therapy as a second-line treatment for r/r LBCL patients who are not considered candidates for stem cell transplant.
“Data from the primary analysis of the PILOT study further demonstrate the potential value of using CAR T-cell therapies earlier in the treatment paradigm for relapsed or refractory LBCL to help improve clinical outcomes and address ongoing unmet need,” he said.
CAR T-cell therapies have shown benefits in later lines for r/r LBCL and as a second-line treatment for r/r LBCL patients who are deemed candidates for stem cell transplant, “so we were encouraged and not surprised by these data.”
However, Dr. Gordon noted, “There may be some patients with similar presentations that might have a transplant, so one limitation of the trial is how one defines patients where transplant is the intended therapy, and that assessment varies among institutions and clinicians.”
An application for liso-cel as a treatment for patients with r/r LBCL who have failed front-line therapy is currently under Priority Review with the FDA, with a Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022, he added.
Liso-cel may fill treatment gap as second-line therapy
The current study is important because “the long-term outcomes of patients with relapsed or refractory large B-cell lymphoma who are not candidates for stem cell transplantation is very poor,” said Dr. Brian Till of Fred Hutchinson Cancer Research Center, Seattle, in an interview.
“CAR T therapy leads to about a 40% cure rate, but is currently only available in this population after the failure of second-line therapy,” said Dr. Till, who was not involved in the study.
“Given that liso-cel was shown to improve outcomes in the second-line setting among transplant candidates, it is logical to consider it as second-line therapy in nontransplant candidates as well, who are otherwise fit enough to receive CAR T therapy,” Dr. Till explained.
“This study showed a rate of long-term progression-free survival similar to what has been observed in the third-line setting and was reasonably well tolerated in these older patients,” said Dr. Till. The results suggest “that second-line liso-cel may be an attractive treatment strategy for patients who are not candidates for stem cell transplantation due to advanced age or comorbidities,” he noted.
Dr. Till had no relevant financial conflicts to disclose.
The study was funded by Bristol Myers Squibb.
Not all patients with relapsed or refractory large B cell lymphoma (r/r LBCL) are candidates for high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT), and options for second-line therapies for this population are limited, said Dr. Alison Sehgal of the University of Pittsburgh Medical Center in her presentation of the findings.
Lisocabtagene maraleucel (liso-cel) is a CD19-directed CAR T-cell product. In a previous phase 3 randomized trial (the TRANSFORM study), lisocabtagene showed superiority over salvage chemotherapy for LBCL patients who were fit candidates for stem cell transplant, but its use in older, frail patients who are not transplant candidates remains uncertain, wrote Dr. Sehgal and colleagues in their poster at the meeting.
In the study, the researchers identified 74 patients with r/r LBCL. Of these, 61 were treated with liso-cel. The patients ranged in age from 53 to 84 years, with a median age of 74 years, 61% were male, and 89% were white. Approximately half were refractory and half were relapsed.
For the therapy, patients underwent lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by an infusion of liso-cel at a target dose of 100 x 106 CAR+ T cells; all patients had at least 6 months of follow-up from their first response.
The primary endpoint of overall response rate occurred in 80% of the patients, and clinically meaningful complete response occurred in 54% over a median follow-up of 12.3 months.
“Clinically meaningful CRs were observed across all subgroups,” Dr. Sehgal said in her presentation.
The response lasted a median of 21.7 months, and the median follow-up for duration of response was 15.5 months. The median overall survival was not reached, but the median progression-free survival was 9.0 months, with a median follow-up period of 13.0 months.
Responses occurred across all prespecified subgroups, with no significant differences in either safety or efficacy based on hematopoietic cell transplantation–specific comorbidity index (HCT-CI) scores.
“Despite the advanced age and comorbidities of the population, the safety profile was consistent with previous reports,” and no new or increased safety signals appeared, Dr. Sehgal said.
The most common treatment-emergent adverse events of grade 3 or higher were neutropenia (48%), leukopenia (21%), thrombocytopenia (20%), and anemia (11%). Cytokine-release syndrome (CRS) occurred in 23 patients (38%); of these, 1 patient was grade 3 and none were grades 4 or 5.
Approximately one-third of the patients (31%) experienced neurological events during the study; three cases were grade 3, none were grades 4 or 5. Patients with CRS or NE were treated with tocilizumab (10%), corticosteroids (3%), or both (20%). Treatment-emergent adverse events of grade 3 or higher occurred in 79% of patients overall, including grade 5 events in two patients because of COVID-19.
The study findings were limited by the small sample size and lack of controls. However, the results support the potential use of liso-cel as a second-line therapy for r/r LBCL patients who are not candidates for HSCT, Dr. Sehgal concluded.
Addressing an ongoing unmet need
In an interview, study coauthor Dr. Leo I. Gordon of Northwestern University, Chicago, observed, “Patients with relapsed or refractory large B-cell lymphoma who are not considered candidates for stem cell transplant following first-line treatment, based on age, comorbidities, health status, or other prognostic factors, have more difficult-to-treat disease, poor prognosis, and more limited treatment options.”
Dr. Gordon noted that the PILOT study is the only trial to evaluate a CAR T-cell therapy as a second-line treatment for r/r LBCL patients who are not considered candidates for stem cell transplant.
“Data from the primary analysis of the PILOT study further demonstrate the potential value of using CAR T-cell therapies earlier in the treatment paradigm for relapsed or refractory LBCL to help improve clinical outcomes and address ongoing unmet need,” he said.
CAR T-cell therapies have shown benefits in later lines for r/r LBCL and as a second-line treatment for r/r LBCL patients who are deemed candidates for stem cell transplant, “so we were encouraged and not surprised by these data.”
However, Dr. Gordon noted, “There may be some patients with similar presentations that might have a transplant, so one limitation of the trial is how one defines patients where transplant is the intended therapy, and that assessment varies among institutions and clinicians.”
An application for liso-cel as a treatment for patients with r/r LBCL who have failed front-line therapy is currently under Priority Review with the FDA, with a Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022, he added.
Liso-cel may fill treatment gap as second-line therapy
The current study is important because “the long-term outcomes of patients with relapsed or refractory large B-cell lymphoma who are not candidates for stem cell transplantation is very poor,” said Dr. Brian Till of Fred Hutchinson Cancer Research Center, Seattle, in an interview.
“CAR T therapy leads to about a 40% cure rate, but is currently only available in this population after the failure of second-line therapy,” said Dr. Till, who was not involved in the study.
“Given that liso-cel was shown to improve outcomes in the second-line setting among transplant candidates, it is logical to consider it as second-line therapy in nontransplant candidates as well, who are otherwise fit enough to receive CAR T therapy,” Dr. Till explained.
“This study showed a rate of long-term progression-free survival similar to what has been observed in the third-line setting and was reasonably well tolerated in these older patients,” said Dr. Till. The results suggest “that second-line liso-cel may be an attractive treatment strategy for patients who are not candidates for stem cell transplantation due to advanced age or comorbidities,” he noted.
Dr. Till had no relevant financial conflicts to disclose.
The study was funded by Bristol Myers Squibb.
Not all patients with relapsed or refractory large B cell lymphoma (r/r LBCL) are candidates for high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT), and options for second-line therapies for this population are limited, said Dr. Alison Sehgal of the University of Pittsburgh Medical Center in her presentation of the findings.
Lisocabtagene maraleucel (liso-cel) is a CD19-directed CAR T-cell product. In a previous phase 3 randomized trial (the TRANSFORM study), lisocabtagene showed superiority over salvage chemotherapy for LBCL patients who were fit candidates for stem cell transplant, but its use in older, frail patients who are not transplant candidates remains uncertain, wrote Dr. Sehgal and colleagues in their poster at the meeting.
In the study, the researchers identified 74 patients with r/r LBCL. Of these, 61 were treated with liso-cel. The patients ranged in age from 53 to 84 years, with a median age of 74 years, 61% were male, and 89% were white. Approximately half were refractory and half were relapsed.
For the therapy, patients underwent lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by an infusion of liso-cel at a target dose of 100 x 106 CAR+ T cells; all patients had at least 6 months of follow-up from their first response.
The primary endpoint of overall response rate occurred in 80% of the patients, and clinically meaningful complete response occurred in 54% over a median follow-up of 12.3 months.
“Clinically meaningful CRs were observed across all subgroups,” Dr. Sehgal said in her presentation.
The response lasted a median of 21.7 months, and the median follow-up for duration of response was 15.5 months. The median overall survival was not reached, but the median progression-free survival was 9.0 months, with a median follow-up period of 13.0 months.
Responses occurred across all prespecified subgroups, with no significant differences in either safety or efficacy based on hematopoietic cell transplantation–specific comorbidity index (HCT-CI) scores.
“Despite the advanced age and comorbidities of the population, the safety profile was consistent with previous reports,” and no new or increased safety signals appeared, Dr. Sehgal said.
The most common treatment-emergent adverse events of grade 3 or higher were neutropenia (48%), leukopenia (21%), thrombocytopenia (20%), and anemia (11%). Cytokine-release syndrome (CRS) occurred in 23 patients (38%); of these, 1 patient was grade 3 and none were grades 4 or 5.
Approximately one-third of the patients (31%) experienced neurological events during the study; three cases were grade 3, none were grades 4 or 5. Patients with CRS or NE were treated with tocilizumab (10%), corticosteroids (3%), or both (20%). Treatment-emergent adverse events of grade 3 or higher occurred in 79% of patients overall, including grade 5 events in two patients because of COVID-19.
The study findings were limited by the small sample size and lack of controls. However, the results support the potential use of liso-cel as a second-line therapy for r/r LBCL patients who are not candidates for HSCT, Dr. Sehgal concluded.
Addressing an ongoing unmet need
In an interview, study coauthor Dr. Leo I. Gordon of Northwestern University, Chicago, observed, “Patients with relapsed or refractory large B-cell lymphoma who are not considered candidates for stem cell transplant following first-line treatment, based on age, comorbidities, health status, or other prognostic factors, have more difficult-to-treat disease, poor prognosis, and more limited treatment options.”
Dr. Gordon noted that the PILOT study is the only trial to evaluate a CAR T-cell therapy as a second-line treatment for r/r LBCL patients who are not considered candidates for stem cell transplant.
“Data from the primary analysis of the PILOT study further demonstrate the potential value of using CAR T-cell therapies earlier in the treatment paradigm for relapsed or refractory LBCL to help improve clinical outcomes and address ongoing unmet need,” he said.
CAR T-cell therapies have shown benefits in later lines for r/r LBCL and as a second-line treatment for r/r LBCL patients who are deemed candidates for stem cell transplant, “so we were encouraged and not surprised by these data.”
However, Dr. Gordon noted, “There may be some patients with similar presentations that might have a transplant, so one limitation of the trial is how one defines patients where transplant is the intended therapy, and that assessment varies among institutions and clinicians.”
An application for liso-cel as a treatment for patients with r/r LBCL who have failed front-line therapy is currently under Priority Review with the FDA, with a Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022, he added.
Liso-cel may fill treatment gap as second-line therapy
The current study is important because “the long-term outcomes of patients with relapsed or refractory large B-cell lymphoma who are not candidates for stem cell transplantation is very poor,” said Dr. Brian Till of Fred Hutchinson Cancer Research Center, Seattle, in an interview.
“CAR T therapy leads to about a 40% cure rate, but is currently only available in this population after the failure of second-line therapy,” said Dr. Till, who was not involved in the study.
“Given that liso-cel was shown to improve outcomes in the second-line setting among transplant candidates, it is logical to consider it as second-line therapy in nontransplant candidates as well, who are otherwise fit enough to receive CAR T therapy,” Dr. Till explained.
“This study showed a rate of long-term progression-free survival similar to what has been observed in the third-line setting and was reasonably well tolerated in these older patients,” said Dr. Till. The results suggest “that second-line liso-cel may be an attractive treatment strategy for patients who are not candidates for stem cell transplantation due to advanced age or comorbidities,” he noted.
Dr. Till had no relevant financial conflicts to disclose.
The study was funded by Bristol Myers Squibb.
FROM ASCO 2022