CLL

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.

Drug shortages in the United States hit a 10-year high in the first quarter of 2023, according to data from the American Society of Health-System Pharmacists (ASHP). Among the top five drug classes affected by shortages are chemotherapy drugs used in the treatment of cancer, many of which do not have alternatives.

“The shortage of certain cancer drugs has become a serious and life-threatening issue for cancer patients across the country,” Karen E. Knudsen, MBA, PhD, chief executive officer of the American Cancer Society (ACS) and its advocacy affiliate, the American Cancer Society Cancer Action Network (ACS CAN), said in a statement. “I have heard from patients and practitioners who are directly experiencing the impact of these shortages.”

As of early May, there were 15 oncology drugs on the official Food and Drug Administration drug shortage list. The other top drug classes on shortage include drugs used for central nervous system (CNS) disorders,  antimicrobials, fluids and electrolytes, and hormones.

Factors blamed for the current shortages include expanded demand, supply shortages, limited manufacturing capacity, and low profit margins for generic therapies.

Dr. Knudsen emphasized that several of the oncology drugs now in short supply do not have an effective alternative. “As first-line treatments for a number of cancers, including triple-negative breast cancer, ovarian cancer, and leukemia often experienced by pediatric cancer patients, the shortage could lead to delays in treatment that could result in worse outcomes,” she said.

The ACS has listed the following oncology drugs and supportive agents as being in short supply: carboplatin injection used to treat triple negative breast cancer, ovarian, head, and neck cancers; fludarabine phosphate injection used for treating B-cell chronic lymphocytic leukemia; dacarbazine injection for treatment of skin cancer; amifostine injection; azacitidine injection; capecitabine tablets; cisplatin injection; cytarabine injection; dexamethasone sodium phosphate injection; hydrocortisone sodium succinate injection; leucovorin calcium lyophilized powder for injection; Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) injection; methotrexate injection; pentostatin injection; and streptozocin (Zanosar) sterile powder.

Many of these drugs, such as cisplatin, are used in multiple regimens, so the issue is not limited to one specific cancer type.

In addition to these drugs, many products used in cancer care such as intravenous saline solutions are also in short supply, the ACS noted.
 

Two decades of shortages

Drug shortages in the United States have been a chronic problem for more than 2 decades, waxing and waning in intensity. In March, a hearing on drug shortages held by the Senate Committee on Homeland Security and Governmental Affairs noted that since 2001, the number of new drug shortages has ranged between 58 (in 2004) and 267 (in 2011). The trend toward new drug shortages declined from 2018 through 2021, but then rose to 160 in 2022.

The report further noted that the first quarter of 2023 marked the highest number of ongoing shortages by quarter since early 2018, with 301 active shortages as of March 31. For some drugs, the problem has become chronic, as more than 15 critical drug products have been in short supply for more than a decade, and 20 have been in shortage since at least 2015.

A 2022 survey of oncology pharmacists at 68 organizations nationwide showed that 63% of institutions reported one or more drug shortages every month, with a 34% increase in 2019, compared with 2018. Treatment delays, reduced doses, or alternative regimens were reported by 75% of respondents, the authors wrote.

Dr. Knudsen noted that the FDA is largely limited to working directly with the manufacturer on whatever issue is causing the shortage, as well as working with other manufacturers of the same product to urge them to ramp up production. 

“ACS CAN is urging Congress to look at longer-term solutions that change the fundamental underpinnings of the shortages,” she said. “In the meantime, we urge the industry to work with medical practitioners to help identify alternatives where possible to ensure that cancer patients’ treatments are not delayed.”
 

A version of this article first appeared on Medscape.com.

Drug shortages in the United States hit a 10-year high in the first quarter of 2023, according to data from the American Society of Health-System Pharmacists (ASHP). Among the top five drug classes affected by shortages are chemotherapy drugs used in the treatment of cancer, many of which do not have alternatives.

“The shortage of certain cancer drugs has become a serious and life-threatening issue for cancer patients across the country,” Karen E. Knudsen, MBA, PhD, chief executive officer of the American Cancer Society (ACS) and its advocacy affiliate, the American Cancer Society Cancer Action Network (ACS CAN), said in a statement. “I have heard from patients and practitioners who are directly experiencing the impact of these shortages.”

As of early May, there were 15 oncology drugs on the official Food and Drug Administration drug shortage list. The other top drug classes on shortage include drugs used for central nervous system (CNS) disorders,  antimicrobials, fluids and electrolytes, and hormones.

Factors blamed for the current shortages include expanded demand, supply shortages, limited manufacturing capacity, and low profit margins for generic therapies.

Dr. Knudsen emphasized that several of the oncology drugs now in short supply do not have an effective alternative. “As first-line treatments for a number of cancers, including triple-negative breast cancer, ovarian cancer, and leukemia often experienced by pediatric cancer patients, the shortage could lead to delays in treatment that could result in worse outcomes,” she said.

The ACS has listed the following oncology drugs and supportive agents as being in short supply: carboplatin injection used to treat triple negative breast cancer, ovarian, head, and neck cancers; fludarabine phosphate injection used for treating B-cell chronic lymphocytic leukemia; dacarbazine injection for treatment of skin cancer; amifostine injection; azacitidine injection; capecitabine tablets; cisplatin injection; cytarabine injection; dexamethasone sodium phosphate injection; hydrocortisone sodium succinate injection; leucovorin calcium lyophilized powder for injection; Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) injection; methotrexate injection; pentostatin injection; and streptozocin (Zanosar) sterile powder.

Many of these drugs, such as cisplatin, are used in multiple regimens, so the issue is not limited to one specific cancer type.

In addition to these drugs, many products used in cancer care such as intravenous saline solutions are also in short supply, the ACS noted.
 

Two decades of shortages

Drug shortages in the United States have been a chronic problem for more than 2 decades, waxing and waning in intensity. In March, a hearing on drug shortages held by the Senate Committee on Homeland Security and Governmental Affairs noted that since 2001, the number of new drug shortages has ranged between 58 (in 2004) and 267 (in 2011). The trend toward new drug shortages declined from 2018 through 2021, but then rose to 160 in 2022.

The report further noted that the first quarter of 2023 marked the highest number of ongoing shortages by quarter since early 2018, with 301 active shortages as of March 31. For some drugs, the problem has become chronic, as more than 15 critical drug products have been in short supply for more than a decade, and 20 have been in shortage since at least 2015.

A 2022 survey of oncology pharmacists at 68 organizations nationwide showed that 63% of institutions reported one or more drug shortages every month, with a 34% increase in 2019, compared with 2018. Treatment delays, reduced doses, or alternative regimens were reported by 75% of respondents, the authors wrote.

Dr. Knudsen noted that the FDA is largely limited to working directly with the manufacturer on whatever issue is causing the shortage, as well as working with other manufacturers of the same product to urge them to ramp up production. 

“ACS CAN is urging Congress to look at longer-term solutions that change the fundamental underpinnings of the shortages,” she said. “In the meantime, we urge the industry to work with medical practitioners to help identify alternatives where possible to ensure that cancer patients’ treatments are not delayed.”
 

A version of this article first appeared on Medscape.com.

Drug shortages in the United States hit a 10-year high in the first quarter of 2023, according to data from the American Society of Health-System Pharmacists (ASHP). Among the top five drug classes affected by shortages are chemotherapy drugs used in the treatment of cancer, many of which do not have alternatives.

“The shortage of certain cancer drugs has become a serious and life-threatening issue for cancer patients across the country,” Karen E. Knudsen, MBA, PhD, chief executive officer of the American Cancer Society (ACS) and its advocacy affiliate, the American Cancer Society Cancer Action Network (ACS CAN), said in a statement. “I have heard from patients and practitioners who are directly experiencing the impact of these shortages.”

As of early May, there were 15 oncology drugs on the official Food and Drug Administration drug shortage list. The other top drug classes on shortage include drugs used for central nervous system (CNS) disorders,  antimicrobials, fluids and electrolytes, and hormones.

Factors blamed for the current shortages include expanded demand, supply shortages, limited manufacturing capacity, and low profit margins for generic therapies.

Dr. Knudsen emphasized that several of the oncology drugs now in short supply do not have an effective alternative. “As first-line treatments for a number of cancers, including triple-negative breast cancer, ovarian cancer, and leukemia often experienced by pediatric cancer patients, the shortage could lead to delays in treatment that could result in worse outcomes,” she said.

The ACS has listed the following oncology drugs and supportive agents as being in short supply: carboplatin injection used to treat triple negative breast cancer, ovarian, head, and neck cancers; fludarabine phosphate injection used for treating B-cell chronic lymphocytic leukemia; dacarbazine injection for treatment of skin cancer; amifostine injection; azacitidine injection; capecitabine tablets; cisplatin injection; cytarabine injection; dexamethasone sodium phosphate injection; hydrocortisone sodium succinate injection; leucovorin calcium lyophilized powder for injection; Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) injection; methotrexate injection; pentostatin injection; and streptozocin (Zanosar) sterile powder.

Many of these drugs, such as cisplatin, are used in multiple regimens, so the issue is not limited to one specific cancer type.

In addition to these drugs, many products used in cancer care such as intravenous saline solutions are also in short supply, the ACS noted.
 

Two decades of shortages

Drug shortages in the United States have been a chronic problem for more than 2 decades, waxing and waning in intensity. In March, a hearing on drug shortages held by the Senate Committee on Homeland Security and Governmental Affairs noted that since 2001, the number of new drug shortages has ranged between 58 (in 2004) and 267 (in 2011). The trend toward new drug shortages declined from 2018 through 2021, but then rose to 160 in 2022.

The report further noted that the first quarter of 2023 marked the highest number of ongoing shortages by quarter since early 2018, with 301 active shortages as of March 31. For some drugs, the problem has become chronic, as more than 15 critical drug products have been in short supply for more than a decade, and 20 have been in shortage since at least 2015.

A 2022 survey of oncology pharmacists at 68 organizations nationwide showed that 63% of institutions reported one or more drug shortages every month, with a 34% increase in 2019, compared with 2018. Treatment delays, reduced doses, or alternative regimens were reported by 75% of respondents, the authors wrote.

Dr. Knudsen noted that the FDA is largely limited to working directly with the manufacturer on whatever issue is causing the shortage, as well as working with other manufacturers of the same product to urge them to ramp up production. 

“ACS CAN is urging Congress to look at longer-term solutions that change the fundamental underpinnings of the shortages,” she said. “In the meantime, we urge the industry to work with medical practitioners to help identify alternatives where possible to ensure that cancer patients’ treatments are not delayed.”
 

A version of this article first appeared on Medscape.com.

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.

The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.

A version of this article first appeared on WebMD.com.

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.

The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.

A version of this article first appeared on WebMD.com.

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.

The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.

A version of this article first appeared on WebMD.com.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

While they’re much less likely to develop chronic lymphocytic leukemia (CLL) than are White patients, African-American patients with this blood cancer are detected later and die sooner from the disease, a new study shows.

The findings, published in the American Journal of Hematology, hint that the racial disparity has shrunk over time, especially within the first few years of the targeted-therapy era. Still, “Black patients had a shorter median overall survival of 7 years compared to 9 years for White patients,” study coauthor Deborah Stephens, DO, of the University of Utah Huntsman Cancer Institute, said in an interview. “Clearly, more research is needed to tease out the biologic or economic barriers to achieving prolonged survival.”

As the researchers noted, CLL is far more common among White patients (5.1 cases per 100,000) than other races (Black patients: 3.2 cases per 100,000; Hispanic patients: 2.1 cases per 100,000; Asian American patients: 1.1 per 100,000). In total, non-White patients make up just 11%-13% of CLL cases in the United States.

According to Dr. Stephens, “little is known or published” about Black patients with CLL, “and it is still a mystery why fewer patients that are Black develop CLL and why this group would have shorter survival.”

Dr. Stephens and colleagues launched the new study – the largest of its kind to date – to understand disparities between White and Black patients over most of the past 20 years. The researchers especially wanted to analyze trends during the last decade, when targeted therapies revolutionized treatment of the disease.

The study authors analyzed data in the National Cancer Database for 97,804 patients diagnosed from 2004 to 2018 (90.7% White, 7.6% Black, 0.6% Asian, 1.1% other). Of patients who reported ethnicity (n = 93,555), 2.6% were Hispanic.

Black patients were more likely to have begun CLL therapy at diagnosis (35.9%) than were White patients (23.6%), a sign that Black patients had more advanced disease. Black patients also had shorter overall survival (7.0 years, 95% confidence interval [CI], 6.7–7.3 years) vs. White patients (9.1 years, 95% CI, 9.0–9.3 years, P < .001).

“This finding could be due to underlying biologic differences in the pathology of CLL, when comparing patients across racial groups,” Dr. Stephens said. “Additionally, there could be differences in access to care. Notably, there are fewer racial minorities enrolled in clinical trials, and perhaps we are not individualizing therapy for unique biologic factors seen in CLL affecting racial minorities.”

Other factors also could be at play. Black patients were more likely than were White patients to have one or more comorbidities (27.9% vs. 21.3%, P < .001), lack insurance (6.6% vs. 2.1%, P < .001) and live in lower-income neighborhoods (47.7% vs. 13.1%, P < .001).

What explains the gap in outcomes? In an interview, study lead author Victoria Vardell, MD, of the University of Utah, Salt Lake City, noted that researchers often attribute worse medical outcomes in Black patients to economic and social disparities.

“However, when we adjusted for a number of surrogate markers of health care access, including income, comorbidities, and location, among others, this disparity remained. That indicates that this may be a more complex problem in CLL in particular. Certainly, we cannot adjust for all the socioeconomic strain placed on Black Americans, including those with CLL, but there may be molecular features related to ancestry or environmental exposures that also play a role,” Dr. Vardell said.

She added that “the high cost and difficulty obtaining many novel therapies, particularly in the clinical trial setting, places significantly higher burdens on already disadvantaged populations.”

There is some good news in the new report. “Promisingly, our data suggest that the survival disparity between White and Black patients with CLL may be improving, particularly within the last 5 years, though longer follow-up is needed to confirm significance,” the researchers reported.

Alessandra Ferrajoli, MD, of M.D. Anderson Cancer Center, Houston, who has studied racial disparities in CLL, praised the study in an interview. As she noted, it examines an impressively large population.

The explanations for the disparities are still elusive, she said, although it seems clear there are multiple factors at play. “We don’t know if the disease has the same characteristics in African-Americans as in Whites,” Dr. Ferrajoli said. However, she noted, there’s “no indication that the response to treatment is different according to race.”

Moving forward, she said, the study findings “reinforce the fact that we need to pay attention to this population and be quite attentive to their characteristics.”

No study funding was reported. The authors and Dr. Ferrajoli have no disclosures.

While they’re much less likely to develop chronic lymphocytic leukemia (CLL) than are White patients, African-American patients with this blood cancer are detected later and die sooner from the disease, a new study shows.

The findings, published in the American Journal of Hematology, hint that the racial disparity has shrunk over time, especially within the first few years of the targeted-therapy era. Still, “Black patients had a shorter median overall survival of 7 years compared to 9 years for White patients,” study coauthor Deborah Stephens, DO, of the University of Utah Huntsman Cancer Institute, said in an interview. “Clearly, more research is needed to tease out the biologic or economic barriers to achieving prolonged survival.”

As the researchers noted, CLL is far more common among White patients (5.1 cases per 100,000) than other races (Black patients: 3.2 cases per 100,000; Hispanic patients: 2.1 cases per 100,000; Asian American patients: 1.1 per 100,000). In total, non-White patients make up just 11%-13% of CLL cases in the United States.

According to Dr. Stephens, “little is known or published” about Black patients with CLL, “and it is still a mystery why fewer patients that are Black develop CLL and why this group would have shorter survival.”

Dr. Stephens and colleagues launched the new study – the largest of its kind to date – to understand disparities between White and Black patients over most of the past 20 years. The researchers especially wanted to analyze trends during the last decade, when targeted therapies revolutionized treatment of the disease.

The study authors analyzed data in the National Cancer Database for 97,804 patients diagnosed from 2004 to 2018 (90.7% White, 7.6% Black, 0.6% Asian, 1.1% other). Of patients who reported ethnicity (n = 93,555), 2.6% were Hispanic.

Black patients were more likely to have begun CLL therapy at diagnosis (35.9%) than were White patients (23.6%), a sign that Black patients had more advanced disease. Black patients also had shorter overall survival (7.0 years, 95% confidence interval [CI], 6.7–7.3 years) vs. White patients (9.1 years, 95% CI, 9.0–9.3 years, P < .001).

“This finding could be due to underlying biologic differences in the pathology of CLL, when comparing patients across racial groups,” Dr. Stephens said. “Additionally, there could be differences in access to care. Notably, there are fewer racial minorities enrolled in clinical trials, and perhaps we are not individualizing therapy for unique biologic factors seen in CLL affecting racial minorities.”

Other factors also could be at play. Black patients were more likely than were White patients to have one or more comorbidities (27.9% vs. 21.3%, P < .001), lack insurance (6.6% vs. 2.1%, P < .001) and live in lower-income neighborhoods (47.7% vs. 13.1%, P < .001).

What explains the gap in outcomes? In an interview, study lead author Victoria Vardell, MD, of the University of Utah, Salt Lake City, noted that researchers often attribute worse medical outcomes in Black patients to economic and social disparities.

“However, when we adjusted for a number of surrogate markers of health care access, including income, comorbidities, and location, among others, this disparity remained. That indicates that this may be a more complex problem in CLL in particular. Certainly, we cannot adjust for all the socioeconomic strain placed on Black Americans, including those with CLL, but there may be molecular features related to ancestry or environmental exposures that also play a role,” Dr. Vardell said.

She added that “the high cost and difficulty obtaining many novel therapies, particularly in the clinical trial setting, places significantly higher burdens on already disadvantaged populations.”

There is some good news in the new report. “Promisingly, our data suggest that the survival disparity between White and Black patients with CLL may be improving, particularly within the last 5 years, though longer follow-up is needed to confirm significance,” the researchers reported.

Alessandra Ferrajoli, MD, of M.D. Anderson Cancer Center, Houston, who has studied racial disparities in CLL, praised the study in an interview. As she noted, it examines an impressively large population.

The explanations for the disparities are still elusive, she said, although it seems clear there are multiple factors at play. “We don’t know if the disease has the same characteristics in African-Americans as in Whites,” Dr. Ferrajoli said. However, she noted, there’s “no indication that the response to treatment is different according to race.”

Moving forward, she said, the study findings “reinforce the fact that we need to pay attention to this population and be quite attentive to their characteristics.”

No study funding was reported. The authors and Dr. Ferrajoli have no disclosures.

While they’re much less likely to develop chronic lymphocytic leukemia (CLL) than are White patients, African-American patients with this blood cancer are detected later and die sooner from the disease, a new study shows.

The findings, published in the American Journal of Hematology, hint that the racial disparity has shrunk over time, especially within the first few years of the targeted-therapy era. Still, “Black patients had a shorter median overall survival of 7 years compared to 9 years for White patients,” study coauthor Deborah Stephens, DO, of the University of Utah Huntsman Cancer Institute, said in an interview. “Clearly, more research is needed to tease out the biologic or economic barriers to achieving prolonged survival.”

As the researchers noted, CLL is far more common among White patients (5.1 cases per 100,000) than other races (Black patients: 3.2 cases per 100,000; Hispanic patients: 2.1 cases per 100,000; Asian American patients: 1.1 per 100,000). In total, non-White patients make up just 11%-13% of CLL cases in the United States.

According to Dr. Stephens, “little is known or published” about Black patients with CLL, “and it is still a mystery why fewer patients that are Black develop CLL and why this group would have shorter survival.”

Dr. Stephens and colleagues launched the new study – the largest of its kind to date – to understand disparities between White and Black patients over most of the past 20 years. The researchers especially wanted to analyze trends during the last decade, when targeted therapies revolutionized treatment of the disease.

The study authors analyzed data in the National Cancer Database for 97,804 patients diagnosed from 2004 to 2018 (90.7% White, 7.6% Black, 0.6% Asian, 1.1% other). Of patients who reported ethnicity (n = 93,555), 2.6% were Hispanic.

Black patients were more likely to have begun CLL therapy at diagnosis (35.9%) than were White patients (23.6%), a sign that Black patients had more advanced disease. Black patients also had shorter overall survival (7.0 years, 95% confidence interval [CI], 6.7–7.3 years) vs. White patients (9.1 years, 95% CI, 9.0–9.3 years, P < .001).

“This finding could be due to underlying biologic differences in the pathology of CLL, when comparing patients across racial groups,” Dr. Stephens said. “Additionally, there could be differences in access to care. Notably, there are fewer racial minorities enrolled in clinical trials, and perhaps we are not individualizing therapy for unique biologic factors seen in CLL affecting racial minorities.”

Other factors also could be at play. Black patients were more likely than were White patients to have one or more comorbidities (27.9% vs. 21.3%, P < .001), lack insurance (6.6% vs. 2.1%, P < .001) and live in lower-income neighborhoods (47.7% vs. 13.1%, P < .001).

What explains the gap in outcomes? In an interview, study lead author Victoria Vardell, MD, of the University of Utah, Salt Lake City, noted that researchers often attribute worse medical outcomes in Black patients to economic and social disparities.

“However, when we adjusted for a number of surrogate markers of health care access, including income, comorbidities, and location, among others, this disparity remained. That indicates that this may be a more complex problem in CLL in particular. Certainly, we cannot adjust for all the socioeconomic strain placed on Black Americans, including those with CLL, but there may be molecular features related to ancestry or environmental exposures that also play a role,” Dr. Vardell said.

She added that “the high cost and difficulty obtaining many novel therapies, particularly in the clinical trial setting, places significantly higher burdens on already disadvantaged populations.”

There is some good news in the new report. “Promisingly, our data suggest that the survival disparity between White and Black patients with CLL may be improving, particularly within the last 5 years, though longer follow-up is needed to confirm significance,” the researchers reported.

Alessandra Ferrajoli, MD, of M.D. Anderson Cancer Center, Houston, who has studied racial disparities in CLL, praised the study in an interview. As she noted, it examines an impressively large population.

The explanations for the disparities are still elusive, she said, although it seems clear there are multiple factors at play. “We don’t know if the disease has the same characteristics in African-Americans as in Whites,” Dr. Ferrajoli said. However, she noted, there’s “no indication that the response to treatment is different according to race.”

Moving forward, she said, the study findings “reinforce the fact that we need to pay attention to this population and be quite attentive to their characteristics.”

No study funding was reported. The authors and Dr. Ferrajoli have no disclosures.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

A version of this article first appeared on WebMD.com.

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

A version of this article first appeared on WebMD.com.

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

A version of this article first appeared on WebMD.com.