COVID-19 infection rates have been nearly 4 times higher among American Indians/Alaska Natives (AI/ANs) when compared with those of non-Hispanic Whites, and AI/ANs are more than 4 times more likely to be hospitalized with the virus. Some mitigation measures have been harder to maintain in Native American communities. Frequent handwashing is difficult when water is at a premium, and social distancing is not always possible when extended families—including elderly—may be living in a single residence.

So vaccination “remains the most promising intervention,” the Indian Health Service Vaccine Task Force wrote in its COVID-19 Pandemic Vaccine Plan, released in November. The plan details how the IHS health care system will prepare for and distribute a vaccine when one becomes available in the US.

The Vaccine Task Force was established by the IHS Headquarters Incident Command Structure, which was activated in early March to respond to COVID-19. In September, the US Department of Health and Human Services (HHS) began a series of consultations with tribes and urban Indian organizations for input on the plan, which aligns as well with recommendations from the Centers for Disease Control and Prevention (CDC).

To “ensure that vaccines are effectively delivered throughout Indian Country in ways that make sense for tribal communities,” HHS Secretary Alex Azar says the Trump Administration has given all tribal health programs and urban Indian organizations two ways to receive the vaccine: through the IHS or through the state.

The CDC, along with IHS, states, and tribes, are coordinating the distribution of a vaccine for federal sites, tribal health programs, and Urban Indian Organizations (UIOs). CDC has issued data requirements that all health care facilities must meet for COVID-19 vaccine administration, inventory, and monitoring.

“There are system-wide planning efforts in place to make sure we’re ready to implement vaccination activities as soon as a US Food and Drug Administration authorized or approved vaccine is available,” said IHS Director RADM Michael Weahkee in a press release. The program’s success, he said, depends on “the strong partnership between the federal government, tribes, and urban leaders.”

The list of IHS, tribal health programs, and UIOs facilities that will receive the COVID-19 vaccine from the IHS, broken down by IHS area, is available on the IHS coronavirus website.

COVID-19 infection rates have been nearly 4 times higher among American Indians/Alaska Natives (AI/ANs) when compared with those of non-Hispanic Whites, and AI/ANs are more than 4 times more likely to be hospitalized with the virus. Some mitigation measures have been harder to maintain in Native American communities. Frequent handwashing is difficult when water is at a premium, and social distancing is not always possible when extended families—including elderly—may be living in a single residence.

So vaccination “remains the most promising intervention,” the Indian Health Service Vaccine Task Force wrote in its COVID-19 Pandemic Vaccine Plan, released in November. The plan details how the IHS health care system will prepare for and distribute a vaccine when one becomes available in the US.

The Vaccine Task Force was established by the IHS Headquarters Incident Command Structure, which was activated in early March to respond to COVID-19. In September, the US Department of Health and Human Services (HHS) began a series of consultations with tribes and urban Indian organizations for input on the plan, which aligns as well with recommendations from the Centers for Disease Control and Prevention (CDC).

To “ensure that vaccines are effectively delivered throughout Indian Country in ways that make sense for tribal communities,” HHS Secretary Alex Azar says the Trump Administration has given all tribal health programs and urban Indian organizations two ways to receive the vaccine: through the IHS or through the state.

The CDC, along with IHS, states, and tribes, are coordinating the distribution of a vaccine for federal sites, tribal health programs, and Urban Indian Organizations (UIOs). CDC has issued data requirements that all health care facilities must meet for COVID-19 vaccine administration, inventory, and monitoring.

“There are system-wide planning efforts in place to make sure we’re ready to implement vaccination activities as soon as a US Food and Drug Administration authorized or approved vaccine is available,” said IHS Director RADM Michael Weahkee in a press release. The program’s success, he said, depends on “the strong partnership between the federal government, tribes, and urban leaders.”

The list of IHS, tribal health programs, and UIOs facilities that will receive the COVID-19 vaccine from the IHS, broken down by IHS area, is available on the IHS coronavirus website.

COVID-19 infection rates have been nearly 4 times higher among American Indians/Alaska Natives (AI/ANs) when compared with those of non-Hispanic Whites, and AI/ANs are more than 4 times more likely to be hospitalized with the virus. Some mitigation measures have been harder to maintain in Native American communities. Frequent handwashing is difficult when water is at a premium, and social distancing is not always possible when extended families—including elderly—may be living in a single residence.

So vaccination “remains the most promising intervention,” the Indian Health Service Vaccine Task Force wrote in its COVID-19 Pandemic Vaccine Plan, released in November. The plan details how the IHS health care system will prepare for and distribute a vaccine when one becomes available in the US.

The Vaccine Task Force was established by the IHS Headquarters Incident Command Structure, which was activated in early March to respond to COVID-19. In September, the US Department of Health and Human Services (HHS) began a series of consultations with tribes and urban Indian organizations for input on the plan, which aligns as well with recommendations from the Centers for Disease Control and Prevention (CDC).

To “ensure that vaccines are effectively delivered throughout Indian Country in ways that make sense for tribal communities,” HHS Secretary Alex Azar says the Trump Administration has given all tribal health programs and urban Indian organizations two ways to receive the vaccine: through the IHS or through the state.

The CDC, along with IHS, states, and tribes, are coordinating the distribution of a vaccine for federal sites, tribal health programs, and Urban Indian Organizations (UIOs). CDC has issued data requirements that all health care facilities must meet for COVID-19 vaccine administration, inventory, and monitoring.

“There are system-wide planning efforts in place to make sure we’re ready to implement vaccination activities as soon as a US Food and Drug Administration authorized or approved vaccine is available,” said IHS Director RADM Michael Weahkee in a press release. The program’s success, he said, depends on “the strong partnership between the federal government, tribes, and urban leaders.”

The list of IHS, tribal health programs, and UIOs facilities that will receive the COVID-19 vaccine from the IHS, broken down by IHS area, is available on the IHS coronavirus website.

The Centers for Disease Control and Prevention (CDC) and Michigan Department of Health and Human Services surveyed health care personnel in 27 hospitals and 7 medical control agencies that coordinate emergency medical services in the Detroit metropolitan area. Of 16,397 participants, 6.9% had COVID-19 antibodies (although only 2.7% reported a history of a positive real-time transcription polymerase chain reaction test); however, participants had about 6 times the odds of exposure to the virus at home when compared with the workplace. Of those who reported close contact (within 6 feet) of a person with confirmed COVID-19 for ≥ 10 minutes, seroprevalence was highest among those with exposure to a household member (34.3%).

The survey revealed a pattern that suggested community acquisition was a common underlying factor of infection risk, the researchers say. Workers were only more vulnerable at home and when they were closer to the metropolitan center. Seropositivity was more common within 9 miles of Detroit’s center, regardless of occupation and health care setting. The farther away from the center, the lower the seroprevalence.

By work location, seroprevalence was highest among participants who worked in hospital wards (8.8%) and lowest among those in police departments (3.9%). In hospitals, participants working in wards and EDs had higher seropositivity (8.8% and 8.1%, respectively) than did those in ICUs and ORs (6.1% and 4.5%, respectively). Nurses and nurse assistants were more likely to be seropositive than physicians. Nurse assistants had the highest incidence, regardless of where they worked.

Reducing community spread through population-based measures may directly protect healthcare workers on 2 fronts, the researchers say: reduced occupational exposure as a result of fewer infected patients in the less controlled workplace setting such as the ED, and reduced exposure in their homes and communities.

The Centers for Disease Control and Prevention (CDC) and Michigan Department of Health and Human Services surveyed health care personnel in 27 hospitals and 7 medical control agencies that coordinate emergency medical services in the Detroit metropolitan area. Of 16,397 participants, 6.9% had COVID-19 antibodies (although only 2.7% reported a history of a positive real-time transcription polymerase chain reaction test); however, participants had about 6 times the odds of exposure to the virus at home when compared with the workplace. Of those who reported close contact (within 6 feet) of a person with confirmed COVID-19 for ≥ 10 minutes, seroprevalence was highest among those with exposure to a household member (34.3%).

The survey revealed a pattern that suggested community acquisition was a common underlying factor of infection risk, the researchers say. Workers were only more vulnerable at home and when they were closer to the metropolitan center. Seropositivity was more common within 9 miles of Detroit’s center, regardless of occupation and health care setting. The farther away from the center, the lower the seroprevalence.

By work location, seroprevalence was highest among participants who worked in hospital wards (8.8%) and lowest among those in police departments (3.9%). In hospitals, participants working in wards and EDs had higher seropositivity (8.8% and 8.1%, respectively) than did those in ICUs and ORs (6.1% and 4.5%, respectively). Nurses and nurse assistants were more likely to be seropositive than physicians. Nurse assistants had the highest incidence, regardless of where they worked.

Reducing community spread through population-based measures may directly protect healthcare workers on 2 fronts, the researchers say: reduced occupational exposure as a result of fewer infected patients in the less controlled workplace setting such as the ED, and reduced exposure in their homes and communities.

The Centers for Disease Control and Prevention (CDC) and Michigan Department of Health and Human Services surveyed health care personnel in 27 hospitals and 7 medical control agencies that coordinate emergency medical services in the Detroit metropolitan area. Of 16,397 participants, 6.9% had COVID-19 antibodies (although only 2.7% reported a history of a positive real-time transcription polymerase chain reaction test); however, participants had about 6 times the odds of exposure to the virus at home when compared with the workplace. Of those who reported close contact (within 6 feet) of a person with confirmed COVID-19 for ≥ 10 minutes, seroprevalence was highest among those with exposure to a household member (34.3%).

The survey revealed a pattern that suggested community acquisition was a common underlying factor of infection risk, the researchers say. Workers were only more vulnerable at home and when they were closer to the metropolitan center. Seropositivity was more common within 9 miles of Detroit’s center, regardless of occupation and health care setting. The farther away from the center, the lower the seroprevalence.

By work location, seroprevalence was highest among participants who worked in hospital wards (8.8%) and lowest among those in police departments (3.9%). In hospitals, participants working in wards and EDs had higher seropositivity (8.8% and 8.1%, respectively) than did those in ICUs and ORs (6.1% and 4.5%, respectively). Nurses and nurse assistants were more likely to be seropositive than physicians. Nurse assistants had the highest incidence, regardless of where they worked.

Reducing community spread through population-based measures may directly protect healthcare workers on 2 fronts, the researchers say: reduced occupational exposure as a result of fewer infected patients in the less controlled workplace setting such as the ED, and reduced exposure in their homes and communities.

The Food and Drug Administration’s new indication for liraglutide (Saxenda) for weight loss in adolescents with obesity, announced on Dec. 4, received welcome as a milestone for advancing a field that’s seen no new drug options since 2003 and boosted by 50% the list of agents indicated for weight loss in this age group.

But liraglutide’s track record in adolescents in the key study published earlier in 2020 left some experts unconvinced that liraglutide’s modest effects would have much impact on blunting the expanding cohort of teens who are obese.

“Until now, we’ve had phentermine and orlistat with FDA approval” for adolescents with obesity, and phentermine’s label specifies only patients older than 16 years. “It’s important that the FDA deemed liraglutide’s benefits greater than its risks for adolescents,” said Aaron S. Kelly, PhD, leader of the 82-week, multicenter, randomized study of liraglutide in 251 adolescents with obesity that directly led to the FDA’s action.

“We have results from a strong, published randomized trial, and the green light from the FDA, and that should give clinicians reassurance and confidence to use liraglutide clinically,” said Dr. Kelly, professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota in Minneapolis.
 

An ‘unimpressive’ drop in BMI

Sonia Caprio, MD, had a more skeptical take on liraglutide’s role with its new indication: “Approval of higher-dose liraglutide is an improvement that reflects a willingness to accept adolescent obesity as a disease that needs treatment with pharmacological agents. However, the study, published in New England Journal of Medicine, was not impressive in terms of weight loss, and more importantly liraglutide was not associated with any significant changes in metabolic markers” such as insulin resistance, high-sensitivity C-reactive protein, lipoproteins and triglycerides, and hemoglobin A1c.

The observed average 5% drop in body mass index seen after a year on liraglutide treatment, compared with baseline and relative to no average change from baseline in the placebo arm, was “totally insufficient, and will not diminish any of the metabolic complications in youth with obesity,” commented Dr. Caprio, an endocrinologist and professor of pediatrics at Yale University in New Haven, Conn.

Results from the study led by Dr. Kelly also showed that liraglutide for 56 weeks cut BMI by 5% in 43% of patients, and by 10% in 26%, compared with respective rates of 19% and 8% among those in the placebo-control arm. He took a more expansive view of the potential benefits from weight loss of the caliber demonstrated by liraglutide in the study.

“In general, we wait too long with obesity in children; the earlier the intervention the better. A 3% or 4% reduction in BMI at 12 or 13 years old can pay big dividends down the road” when a typical adolescent trajectory of steadily rising weight can be flattened, he said in an interview.

Bariatric and metabolic surgery, although highly effective and usually safe, is seen by many clinicians, patients, and families as an “intervention of last resort,” and its very low level of uptake in adolescents bears witness to that reputation. It also creates an important niche for safe and effective drugs to fill as an adjunct to lifestyle changes, which are often ineffective when used by themselves. Liraglutide’s main mechanism for weight loss is depressing hunger, Dr. Kelly noted.
 

Existing meds have limitations

The existing medical treatments, orlistat and phentermine, both have significant drawbacks that limit their use. Orlistat (Xenical, Alli), FDA approved for adolescents 12-16 years old since 2003, limits intestinal fat absorption and as a result often produces unwanted GI effects. Phentermine’s approval for older adolescents dates from 1959 and has a weak evidence base, its label limits it to “short-term” use that’s generally taken to mean a maximum of 12 weeks. And, as a stimulant, phentermine has often been regarded as potentially dangerous, although Dr. Kelly noted that stimulants are well-accepted treatments for other disorders in children and adolescents.

“The earlier we treat obesity in youth, the better, given that it tends to track into adulthood,” agreed Dr. Caprio. “However, it remains to be seen whether weight reduction with a pharmacological agent is going to help prevent the intractable trajectories of weight and its complications. So far, it looks like surgery may be more efficacious,” she said in an interview.

Another drawback for the near future with liraglutide will likely be its cost for many patients, more than $10,000/year at full retail prices for the weight-loss formulation, given that insurers have had a poor record of covering the drug for this indication in adults, both Dr. Caprio and Dr. Kelly noted.

Compliance with liraglutide is also important. Dr. Kelly’s study followed patients for their first 26 weeks off treatment after 56 weeks on the drug, and showed that on average weights rebounded to virtually baseline levels by 6 months after treatment stopped.
 

Obesity treatment lasts a lifetime

“Obesity is a chronic disease, that requires chronic treatment, just like hypertension,” Dr. Kelly stressed, and cited the rebound seen in his study when liraglutide stopped as further proof of that concept. “All obesity treatment is lifelong,” he maintained.

He highlighted the importance of clinicians discussing with adolescent patients and their families the prospect of potentially remaining on liraglutide treatment for years to maintain weight loss. His experience with the randomized study convinced him that many adolescents with obesity are amenable to daily subcutaneous injection using the pen device that liraglutide comes in, but he acknowledged that some teens find this off-putting.

For the near term, Dr. Kelly foresaw liraglutide treatment of adolescents as something that will mostly be administered to patients who seek care at centers that specialize in obesity management. “I’ll think we’ll eventually see it move to more primary care settings, but that will be down the road.”

The study of liraglutide in adolescents was sponsored by Novo Nordisk, the company that markets liraglutide (Saxenda). Dr. Kelly has been a consultant to Novo Nordisk and also to Orexigen Therapeutics, Vivus, and WW, and he has received research funding from AstraZeneca. Dr. Caprio had no disclosures.

[email protected]

The Food and Drug Administration’s new indication for liraglutide (Saxenda) for weight loss in adolescents with obesity, announced on Dec. 4, received welcome as a milestone for advancing a field that’s seen no new drug options since 2003 and boosted by 50% the list of agents indicated for weight loss in this age group.

But liraglutide’s track record in adolescents in the key study published earlier in 2020 left some experts unconvinced that liraglutide’s modest effects would have much impact on blunting the expanding cohort of teens who are obese.

“Until now, we’ve had phentermine and orlistat with FDA approval” for adolescents with obesity, and phentermine’s label specifies only patients older than 16 years. “It’s important that the FDA deemed liraglutide’s benefits greater than its risks for adolescents,” said Aaron S. Kelly, PhD, leader of the 82-week, multicenter, randomized study of liraglutide in 251 adolescents with obesity that directly led to the FDA’s action.

“We have results from a strong, published randomized trial, and the green light from the FDA, and that should give clinicians reassurance and confidence to use liraglutide clinically,” said Dr. Kelly, professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota in Minneapolis.
 

An ‘unimpressive’ drop in BMI

Sonia Caprio, MD, had a more skeptical take on liraglutide’s role with its new indication: “Approval of higher-dose liraglutide is an improvement that reflects a willingness to accept adolescent obesity as a disease that needs treatment with pharmacological agents. However, the study, published in New England Journal of Medicine, was not impressive in terms of weight loss, and more importantly liraglutide was not associated with any significant changes in metabolic markers” such as insulin resistance, high-sensitivity C-reactive protein, lipoproteins and triglycerides, and hemoglobin A1c.

The observed average 5% drop in body mass index seen after a year on liraglutide treatment, compared with baseline and relative to no average change from baseline in the placebo arm, was “totally insufficient, and will not diminish any of the metabolic complications in youth with obesity,” commented Dr. Caprio, an endocrinologist and professor of pediatrics at Yale University in New Haven, Conn.

Results from the study led by Dr. Kelly also showed that liraglutide for 56 weeks cut BMI by 5% in 43% of patients, and by 10% in 26%, compared with respective rates of 19% and 8% among those in the placebo-control arm. He took a more expansive view of the potential benefits from weight loss of the caliber demonstrated by liraglutide in the study.

“In general, we wait too long with obesity in children; the earlier the intervention the better. A 3% or 4% reduction in BMI at 12 or 13 years old can pay big dividends down the road” when a typical adolescent trajectory of steadily rising weight can be flattened, he said in an interview.

Bariatric and metabolic surgery, although highly effective and usually safe, is seen by many clinicians, patients, and families as an “intervention of last resort,” and its very low level of uptake in adolescents bears witness to that reputation. It also creates an important niche for safe and effective drugs to fill as an adjunct to lifestyle changes, which are often ineffective when used by themselves. Liraglutide’s main mechanism for weight loss is depressing hunger, Dr. Kelly noted.
 

Existing meds have limitations

The existing medical treatments, orlistat and phentermine, both have significant drawbacks that limit their use. Orlistat (Xenical, Alli), FDA approved for adolescents 12-16 years old since 2003, limits intestinal fat absorption and as a result often produces unwanted GI effects. Phentermine’s approval for older adolescents dates from 1959 and has a weak evidence base, its label limits it to “short-term” use that’s generally taken to mean a maximum of 12 weeks. And, as a stimulant, phentermine has often been regarded as potentially dangerous, although Dr. Kelly noted that stimulants are well-accepted treatments for other disorders in children and adolescents.

“The earlier we treat obesity in youth, the better, given that it tends to track into adulthood,” agreed Dr. Caprio. “However, it remains to be seen whether weight reduction with a pharmacological agent is going to help prevent the intractable trajectories of weight and its complications. So far, it looks like surgery may be more efficacious,” she said in an interview.

Another drawback for the near future with liraglutide will likely be its cost for many patients, more than $10,000/year at full retail prices for the weight-loss formulation, given that insurers have had a poor record of covering the drug for this indication in adults, both Dr. Caprio and Dr. Kelly noted.

Compliance with liraglutide is also important. Dr. Kelly’s study followed patients for their first 26 weeks off treatment after 56 weeks on the drug, and showed that on average weights rebounded to virtually baseline levels by 6 months after treatment stopped.
 

Obesity treatment lasts a lifetime

“Obesity is a chronic disease, that requires chronic treatment, just like hypertension,” Dr. Kelly stressed, and cited the rebound seen in his study when liraglutide stopped as further proof of that concept. “All obesity treatment is lifelong,” he maintained.

He highlighted the importance of clinicians discussing with adolescent patients and their families the prospect of potentially remaining on liraglutide treatment for years to maintain weight loss. His experience with the randomized study convinced him that many adolescents with obesity are amenable to daily subcutaneous injection using the pen device that liraglutide comes in, but he acknowledged that some teens find this off-putting.

For the near term, Dr. Kelly foresaw liraglutide treatment of adolescents as something that will mostly be administered to patients who seek care at centers that specialize in obesity management. “I’ll think we’ll eventually see it move to more primary care settings, but that will be down the road.”

The study of liraglutide in adolescents was sponsored by Novo Nordisk, the company that markets liraglutide (Saxenda). Dr. Kelly has been a consultant to Novo Nordisk and also to Orexigen Therapeutics, Vivus, and WW, and he has received research funding from AstraZeneca. Dr. Caprio had no disclosures.

[email protected]

The Food and Drug Administration’s new indication for liraglutide (Saxenda) for weight loss in adolescents with obesity, announced on Dec. 4, received welcome as a milestone for advancing a field that’s seen no new drug options since 2003 and boosted by 50% the list of agents indicated for weight loss in this age group.

But liraglutide’s track record in adolescents in the key study published earlier in 2020 left some experts unconvinced that liraglutide’s modest effects would have much impact on blunting the expanding cohort of teens who are obese.

“Until now, we’ve had phentermine and orlistat with FDA approval” for adolescents with obesity, and phentermine’s label specifies only patients older than 16 years. “It’s important that the FDA deemed liraglutide’s benefits greater than its risks for adolescents,” said Aaron S. Kelly, PhD, leader of the 82-week, multicenter, randomized study of liraglutide in 251 adolescents with obesity that directly led to the FDA’s action.

“We have results from a strong, published randomized trial, and the green light from the FDA, and that should give clinicians reassurance and confidence to use liraglutide clinically,” said Dr. Kelly, professor of pediatrics and codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota in Minneapolis.
 

An ‘unimpressive’ drop in BMI

Sonia Caprio, MD, had a more skeptical take on liraglutide’s role with its new indication: “Approval of higher-dose liraglutide is an improvement that reflects a willingness to accept adolescent obesity as a disease that needs treatment with pharmacological agents. However, the study, published in New England Journal of Medicine, was not impressive in terms of weight loss, and more importantly liraglutide was not associated with any significant changes in metabolic markers” such as insulin resistance, high-sensitivity C-reactive protein, lipoproteins and triglycerides, and hemoglobin A1c.

The observed average 5% drop in body mass index seen after a year on liraglutide treatment, compared with baseline and relative to no average change from baseline in the placebo arm, was “totally insufficient, and will not diminish any of the metabolic complications in youth with obesity,” commented Dr. Caprio, an endocrinologist and professor of pediatrics at Yale University in New Haven, Conn.

Results from the study led by Dr. Kelly also showed that liraglutide for 56 weeks cut BMI by 5% in 43% of patients, and by 10% in 26%, compared with respective rates of 19% and 8% among those in the placebo-control arm. He took a more expansive view of the potential benefits from weight loss of the caliber demonstrated by liraglutide in the study.

“In general, we wait too long with obesity in children; the earlier the intervention the better. A 3% or 4% reduction in BMI at 12 or 13 years old can pay big dividends down the road” when a typical adolescent trajectory of steadily rising weight can be flattened, he said in an interview.

Bariatric and metabolic surgery, although highly effective and usually safe, is seen by many clinicians, patients, and families as an “intervention of last resort,” and its very low level of uptake in adolescents bears witness to that reputation. It also creates an important niche for safe and effective drugs to fill as an adjunct to lifestyle changes, which are often ineffective when used by themselves. Liraglutide’s main mechanism for weight loss is depressing hunger, Dr. Kelly noted.
 

Existing meds have limitations

The existing medical treatments, orlistat and phentermine, both have significant drawbacks that limit their use. Orlistat (Xenical, Alli), FDA approved for adolescents 12-16 years old since 2003, limits intestinal fat absorption and as a result often produces unwanted GI effects. Phentermine’s approval for older adolescents dates from 1959 and has a weak evidence base, its label limits it to “short-term” use that’s generally taken to mean a maximum of 12 weeks. And, as a stimulant, phentermine has often been regarded as potentially dangerous, although Dr. Kelly noted that stimulants are well-accepted treatments for other disorders in children and adolescents.

“The earlier we treat obesity in youth, the better, given that it tends to track into adulthood,” agreed Dr. Caprio. “However, it remains to be seen whether weight reduction with a pharmacological agent is going to help prevent the intractable trajectories of weight and its complications. So far, it looks like surgery may be more efficacious,” she said in an interview.

Another drawback for the near future with liraglutide will likely be its cost for many patients, more than $10,000/year at full retail prices for the weight-loss formulation, given that insurers have had a poor record of covering the drug for this indication in adults, both Dr. Caprio and Dr. Kelly noted.

Compliance with liraglutide is also important. Dr. Kelly’s study followed patients for their first 26 weeks off treatment after 56 weeks on the drug, and showed that on average weights rebounded to virtually baseline levels by 6 months after treatment stopped.
 

Obesity treatment lasts a lifetime

“Obesity is a chronic disease, that requires chronic treatment, just like hypertension,” Dr. Kelly stressed, and cited the rebound seen in his study when liraglutide stopped as further proof of that concept. “All obesity treatment is lifelong,” he maintained.

He highlighted the importance of clinicians discussing with adolescent patients and their families the prospect of potentially remaining on liraglutide treatment for years to maintain weight loss. His experience with the randomized study convinced him that many adolescents with obesity are amenable to daily subcutaneous injection using the pen device that liraglutide comes in, but he acknowledged that some teens find this off-putting.

For the near term, Dr. Kelly foresaw liraglutide treatment of adolescents as something that will mostly be administered to patients who seek care at centers that specialize in obesity management. “I’ll think we’ll eventually see it move to more primary care settings, but that will be down the road.”

The study of liraglutide in adolescents was sponsored by Novo Nordisk, the company that markets liraglutide (Saxenda). Dr. Kelly has been a consultant to Novo Nordisk and also to Orexigen Therapeutics, Vivus, and WW, and he has received research funding from AstraZeneca. Dr. Caprio had no disclosures.

[email protected]

Additional results from the THALES trial have shown that 1 month’s dual antiplatelet therapy with ticagrelor (Brilinta; Astra Zeneca) plus aspirin is associated with a reduction in disabling stroke, compared with aspirin alone in patients with minor stroke or high-risk transient ischemic attack (TIA).

Primary results of the THALES trial, published earlier this year in the New England Journal of Medicine, showed a reduction in the primary endpoint of stroke or death within 30 days with the combination of ticagrelor plus aspirin versus aspirin alone, although this was accompanied by an increase in bleeding. In terms of risk/benefit, the main results showed that for every 1,000 patients treatment with ticagrelor on top of aspirin would prevent 11 strokes or deaths at the cost of four severe hemorrhages.

The current exploratory analysis, which focuses on the severity of the strokes occurring in the trial, was published online Nov. 7 in JAMA Neurology to coincide with its presentation at the European Stroke Organisation-World Stroke Organization Conference 2020.

Results showed that, compared with aspirin alone, ticagrelor plus aspirin significantly reduced the 30-day risk for disabling stroke or death (4.0% versus 4.7%), and the total disability burden (the shift analysis of the distribution of modified Rankin scale) following subsequent ischemic stroke was reduced by a significant 23%.

“This new information on disabling stroke underlines the importance of getting patients on dual antiplatelet therapy quickly after a TIA or mild stroke,” said principal investigator of the THALES trial, S. Claiborne Johnston, MD, PhD.

Dr. Johnston, who is dean of Dell Medical School at the University of Texas at Austin, added: “It’s reassuring that ticagrelor has this effect, which was pretty robust. An accompanying editorial to the THALES publication in the NEJM incorrectly stated that ticagrelor did not reduce risk of disabling stroke, so it is good to be able to correct that misconception with this new data.”

Lead author of the exploratory analysis, Pierre Amarenco, MD, professor of neurology at Bichat University Hospital, Paris, added: “The main results showed that ticagrelor on top of aspirin reduced stroke but now we have new information showing reduction in disabling stroke. Obviously, these are the most important types of stroke to prevent. These are the strokes that will impact patients functionally.”

The THALES trial included 11,016 patients with a noncardioembolic, nonsevere ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤ 5) or high-risk TIA, of whom 10,803 had modified Rankin Scale (mRS) functional score recorded at 30 days. 

They were randomized within 24 hours of symptom onset to ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for 1 month) or placebo. All patients received aspirin (300-325 mg on day 1 followed by 75-100 mg daily for 1 month).

In the new analysis, time to occurrence of disabling stroke (mRS greater than 1) or death within 30 days occurred in 221 of 5,511 patients (4.0%) randomized to ticagrelor and in 260 of 5,478 patients (4.7%) randomized to placebo (hazard ratio, 0.83; P = .04).

The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; P = .002).

Factors associated with disability were baseline NIHSS score of 4-5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure.

Asked how the current results compared with observations reported in the main NEJM paper of similar incidences of disability (mRS > 1) in the two groups, Dr. Johnston explained that the result in the original paper looked at disability in the overall population, not just those who went on to have a stroke during follow-up. 

“The problem with looking at overall disability is that most of it is actually from the index stroke (the one that led to the patient being enrolled in the trial). That creates a lot of noise that overwhelms the benefit in reducing disability due to new stroke, the thing we really care about and the subject of the new paper,” he commented.
 

Ticagrelor or clopidogrel?

Ticagrelor now becomes the second antiplatelet agent to have shown benefits on top of aspirin in the minor stroke and high-risk TIA population. Clopidogrel also showed a reduction in major ischemic events in the POINT trial as well as in the Chinese CHANCE trial in similar populations.

Dr. Amarenco pointed out, however, that until now the only treatment that has been shown to reduce disabling stroke in the minor stroke/high risk TIA population in a single trial is aspirin. “The CHANCE and POINT trials of clopidogrel did not show a reduction in disabling stroke individually but this was observed when the trials were combined,” he noted. 

“Clinicians will now have to choose between ticagrelor and clopidogrel. We don’t have a head-to-head comparison yet but ticagrelor is effective in all patients whereas clopidogrel may not be as effective in the large subgroup of patients who carry the loss of function gene which make up about 20% of the western population and about 40% of the Asian population,” he said. 

“It is very important in the acute phase of stroke to know that the antiplatelet drug is immediately effective as the risk of a recurrent event is highest in the first few hours and days.”

Dr. Amarenco acknowledged that some hospitals may favor clopidogrel because of cost, as it is available generically so is much cheaper than ticagrelor. “But we are only talking about 30 days of treatment, so cost is not too much of an issue,” he pointed out.  

The Food and Drug Administration recently approved use of ticagrelor in this indication on the basis of the THALES study.

“It is great news that vascular neurologists now have a new player for reducing future stroke in these patients,” Dr. Amarenco said. Clopidogrel is not approved for this indication but is recommended in American Heart Association/American Stroke Association guidelines, he added.  

Dr. Johnston, who was also the lead investigator of the POINT trial with clopidogrel, suggested that it is more important to get patients on dual-antiplatelet therapy rather than worrying too much about which agent to use. “I think we can use aspirin plus either ticagrelor or clopidogrel. The effect on disabling stroke was not significant in POINT but it did reach significance in a meta-analysis combining POINT and CHANCE,” he noted.

He said that choosing between ticagrelor and clopidogrel is tricky without head-to-head data. “Differences in the studied populations makes direct comparison of the trials unwise,” he stressed.

Dr. Johnston pointed out that neither of the clopidogrel trials included moderate strokes (NIHSS scores of 4 and 5) in their study population. “We only have data on ticagrelor for this important group, which accounted for 30% of the THALES study population,” he noted.

“Some people are concerned about the limited efficacy of clopidogrel in large subgroups of patients who do not metabolize it to its active form, but on the flip side, clopidogrel is cheaper – though a 21- to 30-day course [of ticagrelor] probably isn’t that costly – and has more data in combination with aspirin,” he added.

Dr. Johnston said that the approval of ticagrelor for this new indication was “reassuring,” and “provides some air cover for practitioners given the risks of hemorrhage.” He added: “We didn’t bother with an FDA submission after POINT because it was an NIH-sponsored trial. The drug company normally prioritizes regulatory approvals for marketing purposes but their interests were limited because clopidogrel has exceeded its patent life.”

Cost-utility analyses are not yet available, but Dr. Johnston noted: “I suspect both drugs will have substantial benefits and be cost saving. Stroke is expensive, particularly disabling stroke.”

Dr. Johnston said that the more important message is: “Get these people on dual-antiplatelet therapy as soon as possible. Too many patients are not getting the right treatment immediately after symptom onset. We have lots of work to do here.”
 

Reassuring information

Commenting on the research, J. David Spence, MD, professor of neurology at the Robarts Research Institute, London, Ont., who was not involved in the THALES trial, said this new analysis provided useful and important information that should reassure and encourage clinicians to use dual-antiplatelet therapy in this patient population.

He pointed out that the shift analysis gives the most clinically relevant results. “While the number of patients with a disabling stroke defined as an mRS greater than 1 is lower in the ticagrelor group, I am much more interested in the effect on more severe disability levels – those with an mRS score of 3 or more. Those are the disabilities that we really want to prevent. And from examining the shift analysis distribution, we can see that these more severe disabilities are being reduced with ticagrelor.”

Dr. Spence believes the benefit/risk ratio of dual-antiplatelet therapy could be further improved by better control of blood pressure. “The absolute risk of severe hemorrhage was low in this study, but in my view, most of this could have been prevented by better control of hypertension, as 20 of the 28 severe hemorrhages in the ticagrelor group were intracranial bleeds which can be significantly reduced by good blood pressure control.

“In my view, the increased risk of hemorrhage with dual-antiplatelet therapy should not be regarded as inevitable; it can be virtually eliminated with better medical care,” he stated.

Another outside commentator, Peter Rothwell, MD, PhD, professor of neurology, University of Oxford (England), also believes this is an important paper. “The main NEJM report presented the data on overall disability, but did not present a clear analysis of the effect of ticagrelor plus aspirin on disabling recurrent stroke, but disability in all patients is mainly determined by nonvascular premorbid disability and by the effects of the initial prerandomization stroke. It was highly unlikely that ticagrelor plus aspirin would change these pretrial factors. The only thing that treatment could change was the severity of any posttreatment recurrent stroke, which it did,” he said.

“There is evidence that aspirin plus clopidogrel has the same effect on disabling recurrent stroke. So we now know that ticagrelor plus aspirin also has this effect, which informs consideration of the relative merits of the two treatment strategies,” Dr. Rothwell added.

The THALES trial was sponsored by Astra Zeneca. Dr. Johnston reports support from Sanofi and AstraZeneca outside the submitted work. Dr. Amarenco reports grants and personal fees from AstraZeneca and Bristol-Myers Squibb during the conduct of the study. 

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

Additional results from the THALES trial have shown that 1 month’s dual antiplatelet therapy with ticagrelor (Brilinta; Astra Zeneca) plus aspirin is associated with a reduction in disabling stroke, compared with aspirin alone in patients with minor stroke or high-risk transient ischemic attack (TIA).

Primary results of the THALES trial, published earlier this year in the New England Journal of Medicine, showed a reduction in the primary endpoint of stroke or death within 30 days with the combination of ticagrelor plus aspirin versus aspirin alone, although this was accompanied by an increase in bleeding. In terms of risk/benefit, the main results showed that for every 1,000 patients treatment with ticagrelor on top of aspirin would prevent 11 strokes or deaths at the cost of four severe hemorrhages.

The current exploratory analysis, which focuses on the severity of the strokes occurring in the trial, was published online Nov. 7 in JAMA Neurology to coincide with its presentation at the European Stroke Organisation-World Stroke Organization Conference 2020.

Results showed that, compared with aspirin alone, ticagrelor plus aspirin significantly reduced the 30-day risk for disabling stroke or death (4.0% versus 4.7%), and the total disability burden (the shift analysis of the distribution of modified Rankin scale) following subsequent ischemic stroke was reduced by a significant 23%.

“This new information on disabling stroke underlines the importance of getting patients on dual antiplatelet therapy quickly after a TIA or mild stroke,” said principal investigator of the THALES trial, S. Claiborne Johnston, MD, PhD.

Dr. Johnston, who is dean of Dell Medical School at the University of Texas at Austin, added: “It’s reassuring that ticagrelor has this effect, which was pretty robust. An accompanying editorial to the THALES publication in the NEJM incorrectly stated that ticagrelor did not reduce risk of disabling stroke, so it is good to be able to correct that misconception with this new data.”

Lead author of the exploratory analysis, Pierre Amarenco, MD, professor of neurology at Bichat University Hospital, Paris, added: “The main results showed that ticagrelor on top of aspirin reduced stroke but now we have new information showing reduction in disabling stroke. Obviously, these are the most important types of stroke to prevent. These are the strokes that will impact patients functionally.”

The THALES trial included 11,016 patients with a noncardioembolic, nonsevere ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤ 5) or high-risk TIA, of whom 10,803 had modified Rankin Scale (mRS) functional score recorded at 30 days. 

They were randomized within 24 hours of symptom onset to ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for 1 month) or placebo. All patients received aspirin (300-325 mg on day 1 followed by 75-100 mg daily for 1 month).

In the new analysis, time to occurrence of disabling stroke (mRS greater than 1) or death within 30 days occurred in 221 of 5,511 patients (4.0%) randomized to ticagrelor and in 260 of 5,478 patients (4.7%) randomized to placebo (hazard ratio, 0.83; P = .04).

The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; P = .002).

Factors associated with disability were baseline NIHSS score of 4-5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure.

Asked how the current results compared with observations reported in the main NEJM paper of similar incidences of disability (mRS > 1) in the two groups, Dr. Johnston explained that the result in the original paper looked at disability in the overall population, not just those who went on to have a stroke during follow-up. 

“The problem with looking at overall disability is that most of it is actually from the index stroke (the one that led to the patient being enrolled in the trial). That creates a lot of noise that overwhelms the benefit in reducing disability due to new stroke, the thing we really care about and the subject of the new paper,” he commented.
 

Ticagrelor or clopidogrel?

Ticagrelor now becomes the second antiplatelet agent to have shown benefits on top of aspirin in the minor stroke and high-risk TIA population. Clopidogrel also showed a reduction in major ischemic events in the POINT trial as well as in the Chinese CHANCE trial in similar populations.

Dr. Amarenco pointed out, however, that until now the only treatment that has been shown to reduce disabling stroke in the minor stroke/high risk TIA population in a single trial is aspirin. “The CHANCE and POINT trials of clopidogrel did not show a reduction in disabling stroke individually but this was observed when the trials were combined,” he noted. 

“Clinicians will now have to choose between ticagrelor and clopidogrel. We don’t have a head-to-head comparison yet but ticagrelor is effective in all patients whereas clopidogrel may not be as effective in the large subgroup of patients who carry the loss of function gene which make up about 20% of the western population and about 40% of the Asian population,” he said. 

“It is very important in the acute phase of stroke to know that the antiplatelet drug is immediately effective as the risk of a recurrent event is highest in the first few hours and days.”

Dr. Amarenco acknowledged that some hospitals may favor clopidogrel because of cost, as it is available generically so is much cheaper than ticagrelor. “But we are only talking about 30 days of treatment, so cost is not too much of an issue,” he pointed out.  

The Food and Drug Administration recently approved use of ticagrelor in this indication on the basis of the THALES study.

“It is great news that vascular neurologists now have a new player for reducing future stroke in these patients,” Dr. Amarenco said. Clopidogrel is not approved for this indication but is recommended in American Heart Association/American Stroke Association guidelines, he added.  

Dr. Johnston, who was also the lead investigator of the POINT trial with clopidogrel, suggested that it is more important to get patients on dual-antiplatelet therapy rather than worrying too much about which agent to use. “I think we can use aspirin plus either ticagrelor or clopidogrel. The effect on disabling stroke was not significant in POINT but it did reach significance in a meta-analysis combining POINT and CHANCE,” he noted.

He said that choosing between ticagrelor and clopidogrel is tricky without head-to-head data. “Differences in the studied populations makes direct comparison of the trials unwise,” he stressed.

Dr. Johnston pointed out that neither of the clopidogrel trials included moderate strokes (NIHSS scores of 4 and 5) in their study population. “We only have data on ticagrelor for this important group, which accounted for 30% of the THALES study population,” he noted.

“Some people are concerned about the limited efficacy of clopidogrel in large subgroups of patients who do not metabolize it to its active form, but on the flip side, clopidogrel is cheaper – though a 21- to 30-day course [of ticagrelor] probably isn’t that costly – and has more data in combination with aspirin,” he added.

Dr. Johnston said that the approval of ticagrelor for this new indication was “reassuring,” and “provides some air cover for practitioners given the risks of hemorrhage.” He added: “We didn’t bother with an FDA submission after POINT because it was an NIH-sponsored trial. The drug company normally prioritizes regulatory approvals for marketing purposes but their interests were limited because clopidogrel has exceeded its patent life.”

Cost-utility analyses are not yet available, but Dr. Johnston noted: “I suspect both drugs will have substantial benefits and be cost saving. Stroke is expensive, particularly disabling stroke.”

Dr. Johnston said that the more important message is: “Get these people on dual-antiplatelet therapy as soon as possible. Too many patients are not getting the right treatment immediately after symptom onset. We have lots of work to do here.”
 

Reassuring information

Commenting on the research, J. David Spence, MD, professor of neurology at the Robarts Research Institute, London, Ont., who was not involved in the THALES trial, said this new analysis provided useful and important information that should reassure and encourage clinicians to use dual-antiplatelet therapy in this patient population.

He pointed out that the shift analysis gives the most clinically relevant results. “While the number of patients with a disabling stroke defined as an mRS greater than 1 is lower in the ticagrelor group, I am much more interested in the effect on more severe disability levels – those with an mRS score of 3 or more. Those are the disabilities that we really want to prevent. And from examining the shift analysis distribution, we can see that these more severe disabilities are being reduced with ticagrelor.”

Dr. Spence believes the benefit/risk ratio of dual-antiplatelet therapy could be further improved by better control of blood pressure. “The absolute risk of severe hemorrhage was low in this study, but in my view, most of this could have been prevented by better control of hypertension, as 20 of the 28 severe hemorrhages in the ticagrelor group were intracranial bleeds which can be significantly reduced by good blood pressure control.

“In my view, the increased risk of hemorrhage with dual-antiplatelet therapy should not be regarded as inevitable; it can be virtually eliminated with better medical care,” he stated.

Another outside commentator, Peter Rothwell, MD, PhD, professor of neurology, University of Oxford (England), also believes this is an important paper. “The main NEJM report presented the data on overall disability, but did not present a clear analysis of the effect of ticagrelor plus aspirin on disabling recurrent stroke, but disability in all patients is mainly determined by nonvascular premorbid disability and by the effects of the initial prerandomization stroke. It was highly unlikely that ticagrelor plus aspirin would change these pretrial factors. The only thing that treatment could change was the severity of any posttreatment recurrent stroke, which it did,” he said.

“There is evidence that aspirin plus clopidogrel has the same effect on disabling recurrent stroke. So we now know that ticagrelor plus aspirin also has this effect, which informs consideration of the relative merits of the two treatment strategies,” Dr. Rothwell added.

The THALES trial was sponsored by Astra Zeneca. Dr. Johnston reports support from Sanofi and AstraZeneca outside the submitted work. Dr. Amarenco reports grants and personal fees from AstraZeneca and Bristol-Myers Squibb during the conduct of the study. 

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

Additional results from the THALES trial have shown that 1 month’s dual antiplatelet therapy with ticagrelor (Brilinta; Astra Zeneca) plus aspirin is associated with a reduction in disabling stroke, compared with aspirin alone in patients with minor stroke or high-risk transient ischemic attack (TIA).

Primary results of the THALES trial, published earlier this year in the New England Journal of Medicine, showed a reduction in the primary endpoint of stroke or death within 30 days with the combination of ticagrelor plus aspirin versus aspirin alone, although this was accompanied by an increase in bleeding. In terms of risk/benefit, the main results showed that for every 1,000 patients treatment with ticagrelor on top of aspirin would prevent 11 strokes or deaths at the cost of four severe hemorrhages.

The current exploratory analysis, which focuses on the severity of the strokes occurring in the trial, was published online Nov. 7 in JAMA Neurology to coincide with its presentation at the European Stroke Organisation-World Stroke Organization Conference 2020.

Results showed that, compared with aspirin alone, ticagrelor plus aspirin significantly reduced the 30-day risk for disabling stroke or death (4.0% versus 4.7%), and the total disability burden (the shift analysis of the distribution of modified Rankin scale) following subsequent ischemic stroke was reduced by a significant 23%.

“This new information on disabling stroke underlines the importance of getting patients on dual antiplatelet therapy quickly after a TIA or mild stroke,” said principal investigator of the THALES trial, S. Claiborne Johnston, MD, PhD.

Dr. Johnston, who is dean of Dell Medical School at the University of Texas at Austin, added: “It’s reassuring that ticagrelor has this effect, which was pretty robust. An accompanying editorial to the THALES publication in the NEJM incorrectly stated that ticagrelor did not reduce risk of disabling stroke, so it is good to be able to correct that misconception with this new data.”

Lead author of the exploratory analysis, Pierre Amarenco, MD, professor of neurology at Bichat University Hospital, Paris, added: “The main results showed that ticagrelor on top of aspirin reduced stroke but now we have new information showing reduction in disabling stroke. Obviously, these are the most important types of stroke to prevent. These are the strokes that will impact patients functionally.”

The THALES trial included 11,016 patients with a noncardioembolic, nonsevere ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤ 5) or high-risk TIA, of whom 10,803 had modified Rankin Scale (mRS) functional score recorded at 30 days. 

They were randomized within 24 hours of symptom onset to ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for 1 month) or placebo. All patients received aspirin (300-325 mg on day 1 followed by 75-100 mg daily for 1 month).

In the new analysis, time to occurrence of disabling stroke (mRS greater than 1) or death within 30 days occurred in 221 of 5,511 patients (4.0%) randomized to ticagrelor and in 260 of 5,478 patients (4.7%) randomized to placebo (hazard ratio, 0.83; P = .04).

The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; P = .002).

Factors associated with disability were baseline NIHSS score of 4-5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure.

Asked how the current results compared with observations reported in the main NEJM paper of similar incidences of disability (mRS > 1) in the two groups, Dr. Johnston explained that the result in the original paper looked at disability in the overall population, not just those who went on to have a stroke during follow-up. 

“The problem with looking at overall disability is that most of it is actually from the index stroke (the one that led to the patient being enrolled in the trial). That creates a lot of noise that overwhelms the benefit in reducing disability due to new stroke, the thing we really care about and the subject of the new paper,” he commented.
 

Ticagrelor or clopidogrel?

Ticagrelor now becomes the second antiplatelet agent to have shown benefits on top of aspirin in the minor stroke and high-risk TIA population. Clopidogrel also showed a reduction in major ischemic events in the POINT trial as well as in the Chinese CHANCE trial in similar populations.

Dr. Amarenco pointed out, however, that until now the only treatment that has been shown to reduce disabling stroke in the minor stroke/high risk TIA population in a single trial is aspirin. “The CHANCE and POINT trials of clopidogrel did not show a reduction in disabling stroke individually but this was observed when the trials were combined,” he noted. 

“Clinicians will now have to choose between ticagrelor and clopidogrel. We don’t have a head-to-head comparison yet but ticagrelor is effective in all patients whereas clopidogrel may not be as effective in the large subgroup of patients who carry the loss of function gene which make up about 20% of the western population and about 40% of the Asian population,” he said. 

“It is very important in the acute phase of stroke to know that the antiplatelet drug is immediately effective as the risk of a recurrent event is highest in the first few hours and days.”

Dr. Amarenco acknowledged that some hospitals may favor clopidogrel because of cost, as it is available generically so is much cheaper than ticagrelor. “But we are only talking about 30 days of treatment, so cost is not too much of an issue,” he pointed out.  

The Food and Drug Administration recently approved use of ticagrelor in this indication on the basis of the THALES study.

“It is great news that vascular neurologists now have a new player for reducing future stroke in these patients,” Dr. Amarenco said. Clopidogrel is not approved for this indication but is recommended in American Heart Association/American Stroke Association guidelines, he added.  

Dr. Johnston, who was also the lead investigator of the POINT trial with clopidogrel, suggested that it is more important to get patients on dual-antiplatelet therapy rather than worrying too much about which agent to use. “I think we can use aspirin plus either ticagrelor or clopidogrel. The effect on disabling stroke was not significant in POINT but it did reach significance in a meta-analysis combining POINT and CHANCE,” he noted.

He said that choosing between ticagrelor and clopidogrel is tricky without head-to-head data. “Differences in the studied populations makes direct comparison of the trials unwise,” he stressed.

Dr. Johnston pointed out that neither of the clopidogrel trials included moderate strokes (NIHSS scores of 4 and 5) in their study population. “We only have data on ticagrelor for this important group, which accounted for 30% of the THALES study population,” he noted.

“Some people are concerned about the limited efficacy of clopidogrel in large subgroups of patients who do not metabolize it to its active form, but on the flip side, clopidogrel is cheaper – though a 21- to 30-day course [of ticagrelor] probably isn’t that costly – and has more data in combination with aspirin,” he added.

Dr. Johnston said that the approval of ticagrelor for this new indication was “reassuring,” and “provides some air cover for practitioners given the risks of hemorrhage.” He added: “We didn’t bother with an FDA submission after POINT because it was an NIH-sponsored trial. The drug company normally prioritizes regulatory approvals for marketing purposes but their interests were limited because clopidogrel has exceeded its patent life.”

Cost-utility analyses are not yet available, but Dr. Johnston noted: “I suspect both drugs will have substantial benefits and be cost saving. Stroke is expensive, particularly disabling stroke.”

Dr. Johnston said that the more important message is: “Get these people on dual-antiplatelet therapy as soon as possible. Too many patients are not getting the right treatment immediately after symptom onset. We have lots of work to do here.”
 

Reassuring information

Commenting on the research, J. David Spence, MD, professor of neurology at the Robarts Research Institute, London, Ont., who was not involved in the THALES trial, said this new analysis provided useful and important information that should reassure and encourage clinicians to use dual-antiplatelet therapy in this patient population.

He pointed out that the shift analysis gives the most clinically relevant results. “While the number of patients with a disabling stroke defined as an mRS greater than 1 is lower in the ticagrelor group, I am much more interested in the effect on more severe disability levels – those with an mRS score of 3 or more. Those are the disabilities that we really want to prevent. And from examining the shift analysis distribution, we can see that these more severe disabilities are being reduced with ticagrelor.”

Dr. Spence believes the benefit/risk ratio of dual-antiplatelet therapy could be further improved by better control of blood pressure. “The absolute risk of severe hemorrhage was low in this study, but in my view, most of this could have been prevented by better control of hypertension, as 20 of the 28 severe hemorrhages in the ticagrelor group were intracranial bleeds which can be significantly reduced by good blood pressure control.

“In my view, the increased risk of hemorrhage with dual-antiplatelet therapy should not be regarded as inevitable; it can be virtually eliminated with better medical care,” he stated.

Another outside commentator, Peter Rothwell, MD, PhD, professor of neurology, University of Oxford (England), also believes this is an important paper. “The main NEJM report presented the data on overall disability, but did not present a clear analysis of the effect of ticagrelor plus aspirin on disabling recurrent stroke, but disability in all patients is mainly determined by nonvascular premorbid disability and by the effects of the initial prerandomization stroke. It was highly unlikely that ticagrelor plus aspirin would change these pretrial factors. The only thing that treatment could change was the severity of any posttreatment recurrent stroke, which it did,” he said.

“There is evidence that aspirin plus clopidogrel has the same effect on disabling recurrent stroke. So we now know that ticagrelor plus aspirin also has this effect, which informs consideration of the relative merits of the two treatment strategies,” Dr. Rothwell added.

The THALES trial was sponsored by Astra Zeneca. Dr. Johnston reports support from Sanofi and AstraZeneca outside the submitted work. Dr. Amarenco reports grants and personal fees from AstraZeneca and Bristol-Myers Squibb during the conduct of the study. 

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

Adolescents and young adults with aggressive mature B-cell non-Hodgkin lymphomas appear to have better outcomes when they’re treated under pediatric protocols rather than adult regimens, Canadian investigators say.

Results of a study of patients from the ages of 15 to 21 years with either diffuse large B-cell lymphoma (DLBCL) or Burkitt’s lymphoma treated at regional or community cancer centers in the province of Ontario indicated that adolescents and young adult (AYA) patients treated at adult centers had a more than fourfold risk for disease relapse or progression, compared with their counterparts who were treated at pediatric centers, reported Sumit Gupta, MD, PhD, from the Hospital for Sick Children in Toronto and colleagues.

“Our data suggest that pediatric approaches are associated with improved event-free survival and overall survival, primarily due to a decrease in the risk of relapse or progression, while still using lower cumulative doses of chemotherapy,” he said in an oral abstract presented at the American Society of Hematology annual meeting, held virtually.

The findings echo those seen in the treatment of patients with acute lymphoblastic leukemia (ALL). As previously reported, a study from Nordic and Baltic countries showed that young adults with ALL who were treated with a pediatric regimen had a 4-year event-free survival rate of 73%, compared with 42% for historical controls.

Similarly, a prospective U.S. study reported in 2014 showed that AYA with ALL treated with a pediatric regimen had better overall and event-free survival rates, compared with historical controls.

As with ALL, pediatric and adult regimens for treatment of patients with aggressive mature B-cell NHL differ substantially, with pediatric patients receiving more intensive short-term therapy with lower cumulative doses.

In addition, while pediatric regimens for DLBCL and Burkitt’s lymphoma are identical, adult regimens differ substantially between the two histologies, Dr. Gupta pointed out.

Adult regimens for DLBCL most often incorporate CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP), whereas Burkitt’s lymphoma in adults is generally treated with more aggressive multidrug regimens, in combination with rituximab.

Rituximab was incorporated into adults’ regimens far earlier than in pediatric regimens, with Food and Drug Administration approval of rituximab in frontline therapy of adults with DLBCL in 2006, “whereas the first pediatric large-scale randomized controlled trial of rituximab in pediatric mature B-cell lymphoma was only published earlier this year,” he noted.
 

Population-based study

To see how treatment patterns for AYA patients with aggressive mature B-cell non-Hodgkin lymphomas differ between pediatric and adult centers, Dr. Gupta and colleagues conducted a population-based study of all AYA in Ontario diagnosed with Burkitt’s or DLBCL from the ages of 15 to 21 years from 1992 through 2012.

AYA from the ages of 15 to 18 years who were treated at pediatric centers were identified through the Provincial Pediatric Oncology Registry, which includes data on demographics, disease treatment, and outcomes from each of Ontario’s five childhood cancer treatments centers.

Adolescents and young adults from 15 to 21 years who were treated at adult centers with adult regimens were identified through the Ontario Cancer Registry using chart abstraction by trained personnel at all treatment centers, with all data validated by clinician reviewers.

A total of 176 patients were identified, 129 with DLBCL and 47 with Burkitt’s lymphoma. In all, 62 of the 176 patients (35.2%) were treated in pediatric centers. Not surprisingly, multivariable analysis showed that AYA treated in adult centers were older, and more likely to have been treated earlier in the study period.

Comparing treatment patterns by locus of care, the investigators found that patients with DLBCL in pediatric centers received half of the cumulative anthracycline doses as those in adult centers (150 mg/m² vs. 300 mg/m²; P < .001) and about 75% of cumulative alkylating agent doses (3,300 mg/m² vs. 4,465 mg/m²; P = .009).

Patients with Burkitt’s lymphoma had identical exposures to anthracyclines in pediatric vs. adult centers (120 mg/m²), but those treated in pediatric centers had half the exposure to alkylators as those treated in adult centers (3,300 mg/m² vs. 6,600 mg/m²; P = .03).

Among patients with DLBCL, none of those treated at pediatric centers received rituximab, compared with 32.3% of those treated at adult centers (P < .001), whereas only a handful of patients with Burkitt’s lymphoma received rituximab in both pediatric and adult centers (nonsignificant).

Among all patients. 5-year event-free survival was 82.3% for those treated in pediatric centers, compared with 66.7% for those treated in adult centers (P = .02). Respective 5-year overall survival rates were 85.5% and 71.1% (P = .03).

Looking at survival by histology, the investigators saw that 5-year event-free survival for patients with DLBCL was 83.3% when they were treated like children vs. 66.7% when they were treated like adults (P = .04). Respective 5-year overall survival rates were 88.9% and 72% (P = .04).

Both event-free survival (80.8% vs. 66.7%) and overall survival (80.8% vs. 66.7%) were numerically but not statistically higher among patients with Burkitt’s treated at pediatric vs. adult centers.

An analysis adjusting for disease histology, stage, and time period of diagnosis showed that treatment at an adult center was associated with higher risk for death, with a hazard ratio of 2.4 (P = .03).

Additionally, an analysis adjusted for age, disease stage, and histology showed that patients treated in adult centers had a significantly increased risk of relapse or progression, compared with a HR of 4.4 (95% confidence interval; P = .008).

There were no significant differences in the risk of treatment-related mortality between the center types, however.

“It is important to note, however, that pediatric approaches to mature B-cell NHL [non-Hodgkin lymphoma] are associated with increased inpatient needs as compared to adult approaches, and with greater supportive care requirements. Thus the safety of such approaches in adults centers need to be established,” Dr. Gupta said.
 

Lower doses, better outcomes

In the question and answer session following the presentation, Jennifer Teichman, MD, MSc, a fellow in hematology at the University of Toronto who was not involved in the study asked why patients treated at adult centers would have higher relapse rates despite receiving higher doses of chemotherapy, noting that the poorer outcomes in those patients were not attributable to treatment-related mortality.

“I think one of the distinctions is that higher cumulative doses versus higher intensity of treatment over a shorter period of time are two different things, perhaps, and so giving lower cumulative doses but over a short period of time, and so giving higher intensity within that short period of time, may be what explains the higher success rate in pediatric trials,” Dr. Gupta said.

R. Michael Crump, MD, from the Princess Margaret Cancer Center, also in Toronto, asked whether the study results could have been influenced by differences between the pediatric center and adult center datasets in regard to pathology review, staging information, and International Prognostic Index.

Dr. Gupta acknowledged that, while the pediatric data were captured prospectively at each center by pediatric cancer registry staff and adult data were extracted retrospectively by trained chart reviewers, “the information that we were collecting was relatively basic – basic stage, basic histology, and that is a limitation.”

He also noted that clinicians reviewed the submitted retrospective data for completeness and had the ability to request chart extractors to return to a particular record for additional information or to correct potential errors.

The study was supported by the Canadian Institutes of Health Research, the C17 Council on Children’s Cancer & Blood Disorders, and the Pediatric Oncology Group of Ontario. Dr. Gupta, Dr. Teichman, and Dr. Crump all reported no relevant conflicts of interest.

SOURCE: Gupta S et al. ASH 2020, Abstract 708.

Adolescents and young adults with aggressive mature B-cell non-Hodgkin lymphomas appear to have better outcomes when they’re treated under pediatric protocols rather than adult regimens, Canadian investigators say.

Results of a study of patients from the ages of 15 to 21 years with either diffuse large B-cell lymphoma (DLBCL) or Burkitt’s lymphoma treated at regional or community cancer centers in the province of Ontario indicated that adolescents and young adult (AYA) patients treated at adult centers had a more than fourfold risk for disease relapse or progression, compared with their counterparts who were treated at pediatric centers, reported Sumit Gupta, MD, PhD, from the Hospital for Sick Children in Toronto and colleagues.

“Our data suggest that pediatric approaches are associated with improved event-free survival and overall survival, primarily due to a decrease in the risk of relapse or progression, while still using lower cumulative doses of chemotherapy,” he said in an oral abstract presented at the American Society of Hematology annual meeting, held virtually.

The findings echo those seen in the treatment of patients with acute lymphoblastic leukemia (ALL). As previously reported, a study from Nordic and Baltic countries showed that young adults with ALL who were treated with a pediatric regimen had a 4-year event-free survival rate of 73%, compared with 42% for historical controls.

Similarly, a prospective U.S. study reported in 2014 showed that AYA with ALL treated with a pediatric regimen had better overall and event-free survival rates, compared with historical controls.

As with ALL, pediatric and adult regimens for treatment of patients with aggressive mature B-cell NHL differ substantially, with pediatric patients receiving more intensive short-term therapy with lower cumulative doses.

In addition, while pediatric regimens for DLBCL and Burkitt’s lymphoma are identical, adult regimens differ substantially between the two histologies, Dr. Gupta pointed out.

Adult regimens for DLBCL most often incorporate CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP), whereas Burkitt’s lymphoma in adults is generally treated with more aggressive multidrug regimens, in combination with rituximab.

Rituximab was incorporated into adults’ regimens far earlier than in pediatric regimens, with Food and Drug Administration approval of rituximab in frontline therapy of adults with DLBCL in 2006, “whereas the first pediatric large-scale randomized controlled trial of rituximab in pediatric mature B-cell lymphoma was only published earlier this year,” he noted.
 

Population-based study

To see how treatment patterns for AYA patients with aggressive mature B-cell non-Hodgkin lymphomas differ between pediatric and adult centers, Dr. Gupta and colleagues conducted a population-based study of all AYA in Ontario diagnosed with Burkitt’s or DLBCL from the ages of 15 to 21 years from 1992 through 2012.

AYA from the ages of 15 to 18 years who were treated at pediatric centers were identified through the Provincial Pediatric Oncology Registry, which includes data on demographics, disease treatment, and outcomes from each of Ontario’s five childhood cancer treatments centers.

Adolescents and young adults from 15 to 21 years who were treated at adult centers with adult regimens were identified through the Ontario Cancer Registry using chart abstraction by trained personnel at all treatment centers, with all data validated by clinician reviewers.

A total of 176 patients were identified, 129 with DLBCL and 47 with Burkitt’s lymphoma. In all, 62 of the 176 patients (35.2%) were treated in pediatric centers. Not surprisingly, multivariable analysis showed that AYA treated in adult centers were older, and more likely to have been treated earlier in the study period.

Comparing treatment patterns by locus of care, the investigators found that patients with DLBCL in pediatric centers received half of the cumulative anthracycline doses as those in adult centers (150 mg/m² vs. 300 mg/m²; P < .001) and about 75% of cumulative alkylating agent doses (3,300 mg/m² vs. 4,465 mg/m²; P = .009).

Patients with Burkitt’s lymphoma had identical exposures to anthracyclines in pediatric vs. adult centers (120 mg/m²), but those treated in pediatric centers had half the exposure to alkylators as those treated in adult centers (3,300 mg/m² vs. 6,600 mg/m²; P = .03).

Among patients with DLBCL, none of those treated at pediatric centers received rituximab, compared with 32.3% of those treated at adult centers (P < .001), whereas only a handful of patients with Burkitt’s lymphoma received rituximab in both pediatric and adult centers (nonsignificant).

Among all patients. 5-year event-free survival was 82.3% for those treated in pediatric centers, compared with 66.7% for those treated in adult centers (P = .02). Respective 5-year overall survival rates were 85.5% and 71.1% (P = .03).

Looking at survival by histology, the investigators saw that 5-year event-free survival for patients with DLBCL was 83.3% when they were treated like children vs. 66.7% when they were treated like adults (P = .04). Respective 5-year overall survival rates were 88.9% and 72% (P = .04).

Both event-free survival (80.8% vs. 66.7%) and overall survival (80.8% vs. 66.7%) were numerically but not statistically higher among patients with Burkitt’s treated at pediatric vs. adult centers.

An analysis adjusting for disease histology, stage, and time period of diagnosis showed that treatment at an adult center was associated with higher risk for death, with a hazard ratio of 2.4 (P = .03).

Additionally, an analysis adjusted for age, disease stage, and histology showed that patients treated in adult centers had a significantly increased risk of relapse or progression, compared with a HR of 4.4 (95% confidence interval; P = .008).

There were no significant differences in the risk of treatment-related mortality between the center types, however.

“It is important to note, however, that pediatric approaches to mature B-cell NHL [non-Hodgkin lymphoma] are associated with increased inpatient needs as compared to adult approaches, and with greater supportive care requirements. Thus the safety of such approaches in adults centers need to be established,” Dr. Gupta said.
 

Lower doses, better outcomes

In the question and answer session following the presentation, Jennifer Teichman, MD, MSc, a fellow in hematology at the University of Toronto who was not involved in the study asked why patients treated at adult centers would have higher relapse rates despite receiving higher doses of chemotherapy, noting that the poorer outcomes in those patients were not attributable to treatment-related mortality.

“I think one of the distinctions is that higher cumulative doses versus higher intensity of treatment over a shorter period of time are two different things, perhaps, and so giving lower cumulative doses but over a short period of time, and so giving higher intensity within that short period of time, may be what explains the higher success rate in pediatric trials,” Dr. Gupta said.

R. Michael Crump, MD, from the Princess Margaret Cancer Center, also in Toronto, asked whether the study results could have been influenced by differences between the pediatric center and adult center datasets in regard to pathology review, staging information, and International Prognostic Index.

Dr. Gupta acknowledged that, while the pediatric data were captured prospectively at each center by pediatric cancer registry staff and adult data were extracted retrospectively by trained chart reviewers, “the information that we were collecting was relatively basic – basic stage, basic histology, and that is a limitation.”

He also noted that clinicians reviewed the submitted retrospective data for completeness and had the ability to request chart extractors to return to a particular record for additional information or to correct potential errors.

The study was supported by the Canadian Institutes of Health Research, the C17 Council on Children’s Cancer & Blood Disorders, and the Pediatric Oncology Group of Ontario. Dr. Gupta, Dr. Teichman, and Dr. Crump all reported no relevant conflicts of interest.

SOURCE: Gupta S et al. ASH 2020, Abstract 708.

Adolescents and young adults with aggressive mature B-cell non-Hodgkin lymphomas appear to have better outcomes when they’re treated under pediatric protocols rather than adult regimens, Canadian investigators say.

Results of a study of patients from the ages of 15 to 21 years with either diffuse large B-cell lymphoma (DLBCL) or Burkitt’s lymphoma treated at regional or community cancer centers in the province of Ontario indicated that adolescents and young adult (AYA) patients treated at adult centers had a more than fourfold risk for disease relapse or progression, compared with their counterparts who were treated at pediatric centers, reported Sumit Gupta, MD, PhD, from the Hospital for Sick Children in Toronto and colleagues.

“Our data suggest that pediatric approaches are associated with improved event-free survival and overall survival, primarily due to a decrease in the risk of relapse or progression, while still using lower cumulative doses of chemotherapy,” he said in an oral abstract presented at the American Society of Hematology annual meeting, held virtually.

The findings echo those seen in the treatment of patients with acute lymphoblastic leukemia (ALL). As previously reported, a study from Nordic and Baltic countries showed that young adults with ALL who were treated with a pediatric regimen had a 4-year event-free survival rate of 73%, compared with 42% for historical controls.

Similarly, a prospective U.S. study reported in 2014 showed that AYA with ALL treated with a pediatric regimen had better overall and event-free survival rates, compared with historical controls.

As with ALL, pediatric and adult regimens for treatment of patients with aggressive mature B-cell NHL differ substantially, with pediatric patients receiving more intensive short-term therapy with lower cumulative doses.

In addition, while pediatric regimens for DLBCL and Burkitt’s lymphoma are identical, adult regimens differ substantially between the two histologies, Dr. Gupta pointed out.

Adult regimens for DLBCL most often incorporate CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP), whereas Burkitt’s lymphoma in adults is generally treated with more aggressive multidrug regimens, in combination with rituximab.

Rituximab was incorporated into adults’ regimens far earlier than in pediatric regimens, with Food and Drug Administration approval of rituximab in frontline therapy of adults with DLBCL in 2006, “whereas the first pediatric large-scale randomized controlled trial of rituximab in pediatric mature B-cell lymphoma was only published earlier this year,” he noted.
 

Population-based study

To see how treatment patterns for AYA patients with aggressive mature B-cell non-Hodgkin lymphomas differ between pediatric and adult centers, Dr. Gupta and colleagues conducted a population-based study of all AYA in Ontario diagnosed with Burkitt’s or DLBCL from the ages of 15 to 21 years from 1992 through 2012.

AYA from the ages of 15 to 18 years who were treated at pediatric centers were identified through the Provincial Pediatric Oncology Registry, which includes data on demographics, disease treatment, and outcomes from each of Ontario’s five childhood cancer treatments centers.

Adolescents and young adults from 15 to 21 years who were treated at adult centers with adult regimens were identified through the Ontario Cancer Registry using chart abstraction by trained personnel at all treatment centers, with all data validated by clinician reviewers.

A total of 176 patients were identified, 129 with DLBCL and 47 with Burkitt’s lymphoma. In all, 62 of the 176 patients (35.2%) were treated in pediatric centers. Not surprisingly, multivariable analysis showed that AYA treated in adult centers were older, and more likely to have been treated earlier in the study period.

Comparing treatment patterns by locus of care, the investigators found that patients with DLBCL in pediatric centers received half of the cumulative anthracycline doses as those in adult centers (150 mg/m² vs. 300 mg/m²; P < .001) and about 75% of cumulative alkylating agent doses (3,300 mg/m² vs. 4,465 mg/m²; P = .009).

Patients with Burkitt’s lymphoma had identical exposures to anthracyclines in pediatric vs. adult centers (120 mg/m²), but those treated in pediatric centers had half the exposure to alkylators as those treated in adult centers (3,300 mg/m² vs. 6,600 mg/m²; P = .03).

Among patients with DLBCL, none of those treated at pediatric centers received rituximab, compared with 32.3% of those treated at adult centers (P < .001), whereas only a handful of patients with Burkitt’s lymphoma received rituximab in both pediatric and adult centers (nonsignificant).

Among all patients. 5-year event-free survival was 82.3% for those treated in pediatric centers, compared with 66.7% for those treated in adult centers (P = .02). Respective 5-year overall survival rates were 85.5% and 71.1% (P = .03).

Looking at survival by histology, the investigators saw that 5-year event-free survival for patients with DLBCL was 83.3% when they were treated like children vs. 66.7% when they were treated like adults (P = .04). Respective 5-year overall survival rates were 88.9% and 72% (P = .04).

Both event-free survival (80.8% vs. 66.7%) and overall survival (80.8% vs. 66.7%) were numerically but not statistically higher among patients with Burkitt’s treated at pediatric vs. adult centers.

An analysis adjusting for disease histology, stage, and time period of diagnosis showed that treatment at an adult center was associated with higher risk for death, with a hazard ratio of 2.4 (P = .03).

Additionally, an analysis adjusted for age, disease stage, and histology showed that patients treated in adult centers had a significantly increased risk of relapse or progression, compared with a HR of 4.4 (95% confidence interval; P = .008).

There were no significant differences in the risk of treatment-related mortality between the center types, however.

“It is important to note, however, that pediatric approaches to mature B-cell NHL [non-Hodgkin lymphoma] are associated with increased inpatient needs as compared to adult approaches, and with greater supportive care requirements. Thus the safety of such approaches in adults centers need to be established,” Dr. Gupta said.
 

Lower doses, better outcomes

In the question and answer session following the presentation, Jennifer Teichman, MD, MSc, a fellow in hematology at the University of Toronto who was not involved in the study asked why patients treated at adult centers would have higher relapse rates despite receiving higher doses of chemotherapy, noting that the poorer outcomes in those patients were not attributable to treatment-related mortality.

“I think one of the distinctions is that higher cumulative doses versus higher intensity of treatment over a shorter period of time are two different things, perhaps, and so giving lower cumulative doses but over a short period of time, and so giving higher intensity within that short period of time, may be what explains the higher success rate in pediatric trials,” Dr. Gupta said.

R. Michael Crump, MD, from the Princess Margaret Cancer Center, also in Toronto, asked whether the study results could have been influenced by differences between the pediatric center and adult center datasets in regard to pathology review, staging information, and International Prognostic Index.

Dr. Gupta acknowledged that, while the pediatric data were captured prospectively at each center by pediatric cancer registry staff and adult data were extracted retrospectively by trained chart reviewers, “the information that we were collecting was relatively basic – basic stage, basic histology, and that is a limitation.”

He also noted that clinicians reviewed the submitted retrospective data for completeness and had the ability to request chart extractors to return to a particular record for additional information or to correct potential errors.

The study was supported by the Canadian Institutes of Health Research, the C17 Council on Children’s Cancer & Blood Disorders, and the Pediatric Oncology Group of Ontario. Dr. Gupta, Dr. Teichman, and Dr. Crump all reported no relevant conflicts of interest.

SOURCE: Gupta S et al. ASH 2020, Abstract 708.

Hospitalists in the VA system see patients with symptoms of alcohol withdrawal frequently – there are about 33,000 hospital admissions each year for alcohol withdrawal syndrome (AWS), says Robert Patrick, MD, of the Louis Stokes Cleveland VA Medical Center.

“By contrast, the number of admissions for the largest ambulatory care sensitive condition (heart failure) is only about 28,000,” he said. “If alcohol detox were an ambulatory care sensitive condition, it would be the largest in the VA by a substantial margin.”The purpose of the project he and his co-author, Laura Brown, MD, created to address the problem was to increase the number of patients treated for AWS as outpatients and decrease hospital admissions – without increasing readmissions or clinical deterioration.

They introduced four core operational changes for their study:

1. Standardized risk stratification in the Emergency Department (ED) to identify low risk patients for outpatient treatment.

2. Benzodiazepine sparing symptom triggered medication regimen.

3. Daily clinical dashboard surveillance and risk stratification for continued hospital stay.

4. Telephone follow-up for patients discharged from the ED or hospital.

With these changes in place, eight months of data showed a 50% reduction in AWS admissions and a 40% reduction in length of stays.

Their conclusion? “A well designed and executed QI project can dramatically reduce hospitalist workload, while at the same time improving patient safety,” Dr. Patrick said. “Hospitalists just have to be willing to think outside the box, work with nursing and coordinate care outside of the hospital to make it happen.”

He added a caveat for hospital medicine groups still in a fee-for-service environment. “This saves money for the payer, not the hospital,” he said. “In our case they are one and the same, so the ROI is huge. If you are part of an ACO this is probably true for you, but I would check with your ACO first.”
 

Reference

1. Patrick RM, Brown LZ. Decreasing Admissions, Readmissions and Length of Stay While Improving Patent Safety for Alcohol Withdrawal Syndrome. Abstract published at Hospital Medicine 2019, March 24-27, National Harbor, Md. Abstract Plenary. https://www.shmabstracts.com/abstract/decreasing-admissions-readmissions-and-length-of-stay-while-improving-patient-safety-for-alcohol-withdrawal-syndrome/.

Hospitalists in the VA system see patients with symptoms of alcohol withdrawal frequently – there are about 33,000 hospital admissions each year for alcohol withdrawal syndrome (AWS), says Robert Patrick, MD, of the Louis Stokes Cleveland VA Medical Center.

“By contrast, the number of admissions for the largest ambulatory care sensitive condition (heart failure) is only about 28,000,” he said. “If alcohol detox were an ambulatory care sensitive condition, it would be the largest in the VA by a substantial margin.”The purpose of the project he and his co-author, Laura Brown, MD, created to address the problem was to increase the number of patients treated for AWS as outpatients and decrease hospital admissions – without increasing readmissions or clinical deterioration.

They introduced four core operational changes for their study:

1. Standardized risk stratification in the Emergency Department (ED) to identify low risk patients for outpatient treatment.

2. Benzodiazepine sparing symptom triggered medication regimen.

3. Daily clinical dashboard surveillance and risk stratification for continued hospital stay.

4. Telephone follow-up for patients discharged from the ED or hospital.

With these changes in place, eight months of data showed a 50% reduction in AWS admissions and a 40% reduction in length of stays.

Their conclusion? “A well designed and executed QI project can dramatically reduce hospitalist workload, while at the same time improving patient safety,” Dr. Patrick said. “Hospitalists just have to be willing to think outside the box, work with nursing and coordinate care outside of the hospital to make it happen.”

He added a caveat for hospital medicine groups still in a fee-for-service environment. “This saves money for the payer, not the hospital,” he said. “In our case they are one and the same, so the ROI is huge. If you are part of an ACO this is probably true for you, but I would check with your ACO first.”
 

Reference

1. Patrick RM, Brown LZ. Decreasing Admissions, Readmissions and Length of Stay While Improving Patent Safety for Alcohol Withdrawal Syndrome. Abstract published at Hospital Medicine 2019, March 24-27, National Harbor, Md. Abstract Plenary. https://www.shmabstracts.com/abstract/decreasing-admissions-readmissions-and-length-of-stay-while-improving-patient-safety-for-alcohol-withdrawal-syndrome/.

Hospitalists in the VA system see patients with symptoms of alcohol withdrawal frequently – there are about 33,000 hospital admissions each year for alcohol withdrawal syndrome (AWS), says Robert Patrick, MD, of the Louis Stokes Cleveland VA Medical Center.

“By contrast, the number of admissions for the largest ambulatory care sensitive condition (heart failure) is only about 28,000,” he said. “If alcohol detox were an ambulatory care sensitive condition, it would be the largest in the VA by a substantial margin.”The purpose of the project he and his co-author, Laura Brown, MD, created to address the problem was to increase the number of patients treated for AWS as outpatients and decrease hospital admissions – without increasing readmissions or clinical deterioration.

They introduced four core operational changes for their study:

1. Standardized risk stratification in the Emergency Department (ED) to identify low risk patients for outpatient treatment.

2. Benzodiazepine sparing symptom triggered medication regimen.

3. Daily clinical dashboard surveillance and risk stratification for continued hospital stay.

4. Telephone follow-up for patients discharged from the ED or hospital.

With these changes in place, eight months of data showed a 50% reduction in AWS admissions and a 40% reduction in length of stays.

Their conclusion? “A well designed and executed QI project can dramatically reduce hospitalist workload, while at the same time improving patient safety,” Dr. Patrick said. “Hospitalists just have to be willing to think outside the box, work with nursing and coordinate care outside of the hospital to make it happen.”

He added a caveat for hospital medicine groups still in a fee-for-service environment. “This saves money for the payer, not the hospital,” he said. “In our case they are one and the same, so the ROI is huge. If you are part of an ACO this is probably true for you, but I would check with your ACO first.”
 

Reference

1. Patrick RM, Brown LZ. Decreasing Admissions, Readmissions and Length of Stay While Improving Patent Safety for Alcohol Withdrawal Syndrome. Abstract published at Hospital Medicine 2019, March 24-27, National Harbor, Md. Abstract Plenary. https://www.shmabstracts.com/abstract/decreasing-admissions-readmissions-and-length-of-stay-while-improving-patient-safety-for-alcohol-withdrawal-syndrome/.

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Men with higher-risk prostate cancer have better outcomes, with no increase in long-term toxicity, when a focal radiation boost to the tumor is added to standard external-beam radiation therapy, according to results of the phase 3 FLAME trial.

The results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

FLAME trial details

A total of 571 patients took part in the FLAME trial, which is a collaboration of UMC Utrecht, the Netherlands Cancer Institute, University Hospitals Leuven, and Radboudumc.

The patients were randomized evenly to standard radiation therapy alone (77 Gy to the whole prostate in 35 fractions of 2.2 Gy) or with an integrated boost to the macroscopically visible tumor on multiparametric MRI (to reach a total dose of up to 95 Gy in 35 fractions of 2.7 Gy).

In treatment planning, the organs-at-risk constraints were prioritized over the focal boost dose, Dr. Kerkmeijer pointed out.

A majority of patients (84%) had high-risk disease, and two-thirds received hormonal therapy (usually in the adjuvant setting) with equal distribution across study arms, she reported.

With a median follow-up of 72 months, the 5-year rate of biochemical disease–free survival, the trial’s primary endpoint, was superior with the addition of the focal boost as compared with standard radiation therapy alone (92% vs. 85%; P < .001).

The boost also netted significantly better disease-free survival (P < .001).

The arms were similar on distant metastasis–free survival (P = .26), prostate cancer–specific survival (P = .49), and overall survival (P = .50), although longer follow-up is needed to fully assess these outcomes, Dr. Kerkmeijer noted.

The boost and standard therapy arms had much the same late grade 3 or higher genitourinary toxicity (5.6% vs. 3.5%; P = .22) and late grade 3 or higher gastrointestinal toxicity (1.4% vs. 1.4%; P = .99).

The arms were essentially identical on long-term patient-reported urinary symptoms, bowel symptoms, sexual activity, and sexual function, as measured with the EORTC QLQ-PR25 tool and detailed in a companion presentation (abstract OC-0315).
 

‘A standard option’ and next steps

“FLAME is the first phase 3 randomized controlled trial to show that focal boosting works and that biochemical recurrence was reduced at 5 years,” Dr. Kerkmeijer said. “We propose that the FLAME scheme can be considered as a standard option for patients with intermediate- but especially high-risk prostate cancer.”

“For patients, biochemical recurrence may have impact, as this causes additional follow-up and diagnostic exams, potential anxiety, and potential side effects of subsequent treatments,” she added. “Biochemical recurrences were reduced by almost half and at no additional cost and no additional toxicity by this FLAME isotoxic approach and by using conventional radiotherapy techniques.”

The next step is pairing the boost with ultra-hypofractionation, which requires highly accurate targeting, Dr. Kerkmeijer said. In fact, favorable early toxicity results of the subsequent Hypo-FLAME trial, which tested this strategy, were also reported at the congress (abstract OC-0209), and a trial taking the strategy even further, Hypo-FLAME 2.0, is ongoing.

“The FLAME trial’s results are probably true but may have been impacted by the use of hormonal therapy,” Anthony V. D’Amico, MD, PhD, of the Dana Farber Cancer Institute and Harvard Medical School, Boston, said in an interview.

SOURCE: De Boer HCJ et al. ESTRO 2020. Abstract OC-0612.

Men with higher-risk prostate cancer have better outcomes, with no increase in long-term toxicity, when a focal radiation boost to the tumor is added to standard external-beam radiation therapy, according to results of the phase 3 FLAME trial.

The results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

FLAME trial details

A total of 571 patients took part in the FLAME trial, which is a collaboration of UMC Utrecht, the Netherlands Cancer Institute, University Hospitals Leuven, and Radboudumc.

The patients were randomized evenly to standard radiation therapy alone (77 Gy to the whole prostate in 35 fractions of 2.2 Gy) or with an integrated boost to the macroscopically visible tumor on multiparametric MRI (to reach a total dose of up to 95 Gy in 35 fractions of 2.7 Gy).

In treatment planning, the organs-at-risk constraints were prioritized over the focal boost dose, Dr. Kerkmeijer pointed out.

A majority of patients (84%) had high-risk disease, and two-thirds received hormonal therapy (usually in the adjuvant setting) with equal distribution across study arms, she reported.

With a median follow-up of 72 months, the 5-year rate of biochemical disease–free survival, the trial’s primary endpoint, was superior with the addition of the focal boost as compared with standard radiation therapy alone (92% vs. 85%; P < .001).

The boost also netted significantly better disease-free survival (P < .001).

The arms were similar on distant metastasis–free survival (P = .26), prostate cancer–specific survival (P = .49), and overall survival (P = .50), although longer follow-up is needed to fully assess these outcomes, Dr. Kerkmeijer noted.

The boost and standard therapy arms had much the same late grade 3 or higher genitourinary toxicity (5.6% vs. 3.5%; P = .22) and late grade 3 or higher gastrointestinal toxicity (1.4% vs. 1.4%; P = .99).

The arms were essentially identical on long-term patient-reported urinary symptoms, bowel symptoms, sexual activity, and sexual function, as measured with the EORTC QLQ-PR25 tool and detailed in a companion presentation (abstract OC-0315).
 

‘A standard option’ and next steps

“FLAME is the first phase 3 randomized controlled trial to show that focal boosting works and that biochemical recurrence was reduced at 5 years,” Dr. Kerkmeijer said. “We propose that the FLAME scheme can be considered as a standard option for patients with intermediate- but especially high-risk prostate cancer.”

“For patients, biochemical recurrence may have impact, as this causes additional follow-up and diagnostic exams, potential anxiety, and potential side effects of subsequent treatments,” she added. “Biochemical recurrences were reduced by almost half and at no additional cost and no additional toxicity by this FLAME isotoxic approach and by using conventional radiotherapy techniques.”

The next step is pairing the boost with ultra-hypofractionation, which requires highly accurate targeting, Dr. Kerkmeijer said. In fact, favorable early toxicity results of the subsequent Hypo-FLAME trial, which tested this strategy, were also reported at the congress (abstract OC-0209), and a trial taking the strategy even further, Hypo-FLAME 2.0, is ongoing.

“The FLAME trial’s results are probably true but may have been impacted by the use of hormonal therapy,” Anthony V. D’Amico, MD, PhD, of the Dana Farber Cancer Institute and Harvard Medical School, Boston, said in an interview.

SOURCE: De Boer HCJ et al. ESTRO 2020. Abstract OC-0612.

Men with higher-risk prostate cancer have better outcomes, with no increase in long-term toxicity, when a focal radiation boost to the tumor is added to standard external-beam radiation therapy, according to results of the phase 3 FLAME trial.

The results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

FLAME trial details

A total of 571 patients took part in the FLAME trial, which is a collaboration of UMC Utrecht, the Netherlands Cancer Institute, University Hospitals Leuven, and Radboudumc.

The patients were randomized evenly to standard radiation therapy alone (77 Gy to the whole prostate in 35 fractions of 2.2 Gy) or with an integrated boost to the macroscopically visible tumor on multiparametric MRI (to reach a total dose of up to 95 Gy in 35 fractions of 2.7 Gy).

In treatment planning, the organs-at-risk constraints were prioritized over the focal boost dose, Dr. Kerkmeijer pointed out.

A majority of patients (84%) had high-risk disease, and two-thirds received hormonal therapy (usually in the adjuvant setting) with equal distribution across study arms, she reported.

With a median follow-up of 72 months, the 5-year rate of biochemical disease–free survival, the trial’s primary endpoint, was superior with the addition of the focal boost as compared with standard radiation therapy alone (92% vs. 85%; P < .001).

The boost also netted significantly better disease-free survival (P < .001).

The arms were similar on distant metastasis–free survival (P = .26), prostate cancer–specific survival (P = .49), and overall survival (P = .50), although longer follow-up is needed to fully assess these outcomes, Dr. Kerkmeijer noted.

The boost and standard therapy arms had much the same late grade 3 or higher genitourinary toxicity (5.6% vs. 3.5%; P = .22) and late grade 3 or higher gastrointestinal toxicity (1.4% vs. 1.4%; P = .99).

The arms were essentially identical on long-term patient-reported urinary symptoms, bowel symptoms, sexual activity, and sexual function, as measured with the EORTC QLQ-PR25 tool and detailed in a companion presentation (abstract OC-0315).
 

‘A standard option’ and next steps

“FLAME is the first phase 3 randomized controlled trial to show that focal boosting works and that biochemical recurrence was reduced at 5 years,” Dr. Kerkmeijer said. “We propose that the FLAME scheme can be considered as a standard option for patients with intermediate- but especially high-risk prostate cancer.”

“For patients, biochemical recurrence may have impact, as this causes additional follow-up and diagnostic exams, potential anxiety, and potential side effects of subsequent treatments,” she added. “Biochemical recurrences were reduced by almost half and at no additional cost and no additional toxicity by this FLAME isotoxic approach and by using conventional radiotherapy techniques.”

The next step is pairing the boost with ultra-hypofractionation, which requires highly accurate targeting, Dr. Kerkmeijer said. In fact, favorable early toxicity results of the subsequent Hypo-FLAME trial, which tested this strategy, were also reported at the congress (abstract OC-0209), and a trial taking the strategy even further, Hypo-FLAME 2.0, is ongoing.

“The FLAME trial’s results are probably true but may have been impacted by the use of hormonal therapy,” Anthony V. D’Amico, MD, PhD, of the Dana Farber Cancer Institute and Harvard Medical School, Boston, said in an interview.

SOURCE: De Boer HCJ et al. ESTRO 2020. Abstract OC-0612.

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.

Merkel cell carcinoma (MCC) is infamous for what Manisha Thakuria, MD, described as “large, frightening looking tumors,” but its variable appearance makes it challenging to diagnose.

“The lack of a pathognomonic appearance is often what precludes an early diagnosis of this cancer,” Dr. Thakuria, a dermatologist at Brigham and Women’s Hospital, Boston, said during a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and the Global Academy for Medical Education. “MCCs can vary in appearance in their color, from pink to red to purple, or sometimes they have no color at all. They can be exophytic and obvious, or subtle, deeper tumors. These tumors are generally firm and nontender and are characterized by rapid growth, which is usually but not exclusively the feature that prompts biopsy.”

The typical patient with MCC is elderly, with an average age of 75 years. It affects males more than females by an approximately 2:1 ratio and tends to occur in fair-skinned individuals, although MCC does develop in skin of color. “While the majority of patients with this disease are immunocompetent, immunosuppressed patients are overrepresented in this disease, compared with the general population,” she said.

The clinical differential diagnosis is broad and includes both malignant and benign tumors, which requires a high index of suspicion. Most primary lesions are located on the head and neck, lower limb, and upper limb, but they may appear in non–sun exposed areas, such as the buttocks, as well.

One prospective study of 195 MCC patients found that 56% of clinicians presumed that these tumors were benign at the time of biopsy, and 32% were thought to have a cyst or acneiform lesion. The study authors summarized key clinical features of MCC with the acronym AEIOU: A stands for asymptomatic or nontender; E stands for expanding rapidly, usually over a duration less than 3 months; I stands for immunosuppression; O stands for patient older than age 50 years; and U stands for UV exposed skin location. The researchers found that 89% of the patients studied met three or more of the AEIOU criteria.

Dr. Thakuria, codirector of the Merkel Cell Carcinoma Center of Excellence at the Dana-Farber/Brigham and Women’s Cancer Center and assistant professor of dermatology at Harvard University, both in Boston, shared the following tips for dermatologic evaluation when MCC is suspected:
 

• Measure and record the clinical diameter of the lesions. “This helps you determine the T staging later, and from there can help you decide on proper treatment,” she said.
• Inspect and palpate the surrounding skin to look for in-transit metastases. “This may actually upstage the patient.”
• For a subcutaneous nodule, hub your punch biopsy. “These tumors can be centered in the deep dermis or fat,” Dr. Thakuria said. “If you really suspect MCC and you don’t get a result on your first biopsy, you may want to consider doing a second deeper biopsy, perhaps even a telescoping biopsy. This is especially true if your first biopsy was via shave technique and showed normal skin.”
• Refer to surgical oncology and radiation oncology ASAP. “You want to call them to ensure speedy consultation, within 1 week if possible,” she said. “Remember that all clinically node-negative MCCs warrant consideration of sentinel lymph node biopsy, regardless of tumor size. Upstaging will occur in 25%-32% of patients.”

Staging workup includes a full skin and lymph node exam to identify in-transit metastases and regional lymphadenopathy. “Palpation is key,” Dr. Thakuria said. “Next, you want to do some form of radiographic examination, so either a scalp to toes PET/CT or CT scan of the chest, abdomen, and pelvis. Finally, sentinel lymph node biopsy is going to be important if you have a clinically node-negative patient but you want to pathologically stage the person appropriately.” Although not formally part of the staging workup, she recommends ordering an AMERK test at diagnosis. AMERK detects antibodies to a Merkel cell polyomavirus oncoprotein, which is a marker of disease status present in about half of MCC patients. It falls with the treatment of cancer and rises with recurrence.

Discussing prognosis with MCC patients “can be challenging and uncomfortable, but even more so if you’re unfamiliar with some of the nuances of the terminology that is used,” Dr. Thakuria said. “Patients who go to Google are often going to encounter overall survival numbers, which are going to be worse than disease-specific numbers in any disease because they take into account death from any cause. This effect is heightened in MCC because this is cancer of predominately older adults, so there are other competing causes of death in this population, which drags down the overall survival estimates.”

Another point to remember when discussing survival with patients is that advances in immunotherapy are not necessarily reflected in national databases. “This is important, because usually in any cancer there’s a 5- to 10-year lag in survival information,” she said. “The last 5 years have brought an incredible change to MCC because of the advent of immunotherapy. Now we’re seeing incredible responses [in the clinic], but we’re not yet seeing those reflected in our survival tables.”

According to an analysis of prognostic factors from 9,387 MCC cases, nodal status is one of most important predictors of lower survival at 5 years, compared with having local disease: 35% versus 51%, respectively. Among patients with macroscopic lymph nodes, having known primary disease is associated with a lower survival at 5 years, compared with having unknown primary disease (27% vs. 42% at five years).

Dr. Thakuria concluded her presentation by recommending a three-step plan for surveillance, starting with a full skin and lymph node exam every 3-6 months for the first 3 years and every 6-12 months thereafter. Second, she advised routine imaging for high risk patients (American Joint Committee on Cancer stage 2 and above) and symptom-directed imaging for low-risk patients. Finally, she recommended the AMERK test every 3 months for the first 2-3 years in patients who were seropositive at diagnosis. A rising titer may be an early indicator of recurrence.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Thakuria reported having no financial disclosures.
 

[email protected]

Merkel cell carcinoma (MCC) is infamous for what Manisha Thakuria, MD, described as “large, frightening looking tumors,” but its variable appearance makes it challenging to diagnose.

“The lack of a pathognomonic appearance is often what precludes an early diagnosis of this cancer,” Dr. Thakuria, a dermatologist at Brigham and Women’s Hospital, Boston, said during a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and the Global Academy for Medical Education. “MCCs can vary in appearance in their color, from pink to red to purple, or sometimes they have no color at all. They can be exophytic and obvious, or subtle, deeper tumors. These tumors are generally firm and nontender and are characterized by rapid growth, which is usually but not exclusively the feature that prompts biopsy.”

The typical patient with MCC is elderly, with an average age of 75 years. It affects males more than females by an approximately 2:1 ratio and tends to occur in fair-skinned individuals, although MCC does develop in skin of color. “While the majority of patients with this disease are immunocompetent, immunosuppressed patients are overrepresented in this disease, compared with the general population,” she said.

The clinical differential diagnosis is broad and includes both malignant and benign tumors, which requires a high index of suspicion. Most primary lesions are located on the head and neck, lower limb, and upper limb, but they may appear in non–sun exposed areas, such as the buttocks, as well.

One prospective study of 195 MCC patients found that 56% of clinicians presumed that these tumors were benign at the time of biopsy, and 32% were thought to have a cyst or acneiform lesion. The study authors summarized key clinical features of MCC with the acronym AEIOU: A stands for asymptomatic or nontender; E stands for expanding rapidly, usually over a duration less than 3 months; I stands for immunosuppression; O stands for patient older than age 50 years; and U stands for UV exposed skin location. The researchers found that 89% of the patients studied met three or more of the AEIOU criteria.

Dr. Thakuria, codirector of the Merkel Cell Carcinoma Center of Excellence at the Dana-Farber/Brigham and Women’s Cancer Center and assistant professor of dermatology at Harvard University, both in Boston, shared the following tips for dermatologic evaluation when MCC is suspected:
 

• Measure and record the clinical diameter of the lesions. “This helps you determine the T staging later, and from there can help you decide on proper treatment,” she said.
• Inspect and palpate the surrounding skin to look for in-transit metastases. “This may actually upstage the patient.”
• For a subcutaneous nodule, hub your punch biopsy. “These tumors can be centered in the deep dermis or fat,” Dr. Thakuria said. “If you really suspect MCC and you don’t get a result on your first biopsy, you may want to consider doing a second deeper biopsy, perhaps even a telescoping biopsy. This is especially true if your first biopsy was via shave technique and showed normal skin.”
• Refer to surgical oncology and radiation oncology ASAP. “You want to call them to ensure speedy consultation, within 1 week if possible,” she said. “Remember that all clinically node-negative MCCs warrant consideration of sentinel lymph node biopsy, regardless of tumor size. Upstaging will occur in 25%-32% of patients.”

Staging workup includes a full skin and lymph node exam to identify in-transit metastases and regional lymphadenopathy. “Palpation is key,” Dr. Thakuria said. “Next, you want to do some form of radiographic examination, so either a scalp to toes PET/CT or CT scan of the chest, abdomen, and pelvis. Finally, sentinel lymph node biopsy is going to be important if you have a clinically node-negative patient but you want to pathologically stage the person appropriately.” Although not formally part of the staging workup, she recommends ordering an AMERK test at diagnosis. AMERK detects antibodies to a Merkel cell polyomavirus oncoprotein, which is a marker of disease status present in about half of MCC patients. It falls with the treatment of cancer and rises with recurrence.

Discussing prognosis with MCC patients “can be challenging and uncomfortable, but even more so if you’re unfamiliar with some of the nuances of the terminology that is used,” Dr. Thakuria said. “Patients who go to Google are often going to encounter overall survival numbers, which are going to be worse than disease-specific numbers in any disease because they take into account death from any cause. This effect is heightened in MCC because this is cancer of predominately older adults, so there are other competing causes of death in this population, which drags down the overall survival estimates.”

Another point to remember when discussing survival with patients is that advances in immunotherapy are not necessarily reflected in national databases. “This is important, because usually in any cancer there’s a 5- to 10-year lag in survival information,” she said. “The last 5 years have brought an incredible change to MCC because of the advent of immunotherapy. Now we’re seeing incredible responses [in the clinic], but we’re not yet seeing those reflected in our survival tables.”

According to an analysis of prognostic factors from 9,387 MCC cases, nodal status is one of most important predictors of lower survival at 5 years, compared with having local disease: 35% versus 51%, respectively. Among patients with macroscopic lymph nodes, having known primary disease is associated with a lower survival at 5 years, compared with having unknown primary disease (27% vs. 42% at five years).

Dr. Thakuria concluded her presentation by recommending a three-step plan for surveillance, starting with a full skin and lymph node exam every 3-6 months for the first 3 years and every 6-12 months thereafter. Second, she advised routine imaging for high risk patients (American Joint Committee on Cancer stage 2 and above) and symptom-directed imaging for low-risk patients. Finally, she recommended the AMERK test every 3 months for the first 2-3 years in patients who were seropositive at diagnosis. A rising titer may be an early indicator of recurrence.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Thakuria reported having no financial disclosures.
 

[email protected]

Merkel cell carcinoma (MCC) is infamous for what Manisha Thakuria, MD, described as “large, frightening looking tumors,” but its variable appearance makes it challenging to diagnose.

“The lack of a pathognomonic appearance is often what precludes an early diagnosis of this cancer,” Dr. Thakuria, a dermatologist at Brigham and Women’s Hospital, Boston, said during a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and the Global Academy for Medical Education. “MCCs can vary in appearance in their color, from pink to red to purple, or sometimes they have no color at all. They can be exophytic and obvious, or subtle, deeper tumors. These tumors are generally firm and nontender and are characterized by rapid growth, which is usually but not exclusively the feature that prompts biopsy.”

The typical patient with MCC is elderly, with an average age of 75 years. It affects males more than females by an approximately 2:1 ratio and tends to occur in fair-skinned individuals, although MCC does develop in skin of color. “While the majority of patients with this disease are immunocompetent, immunosuppressed patients are overrepresented in this disease, compared with the general population,” she said.

The clinical differential diagnosis is broad and includes both malignant and benign tumors, which requires a high index of suspicion. Most primary lesions are located on the head and neck, lower limb, and upper limb, but they may appear in non–sun exposed areas, such as the buttocks, as well.

One prospective study of 195 MCC patients found that 56% of clinicians presumed that these tumors were benign at the time of biopsy, and 32% were thought to have a cyst or acneiform lesion. The study authors summarized key clinical features of MCC with the acronym AEIOU: A stands for asymptomatic or nontender; E stands for expanding rapidly, usually over a duration less than 3 months; I stands for immunosuppression; O stands for patient older than age 50 years; and U stands for UV exposed skin location. The researchers found that 89% of the patients studied met three or more of the AEIOU criteria.

Dr. Thakuria, codirector of the Merkel Cell Carcinoma Center of Excellence at the Dana-Farber/Brigham and Women’s Cancer Center and assistant professor of dermatology at Harvard University, both in Boston, shared the following tips for dermatologic evaluation when MCC is suspected:
 

• Measure and record the clinical diameter of the lesions. “This helps you determine the T staging later, and from there can help you decide on proper treatment,” she said.
• Inspect and palpate the surrounding skin to look for in-transit metastases. “This may actually upstage the patient.”
• For a subcutaneous nodule, hub your punch biopsy. “These tumors can be centered in the deep dermis or fat,” Dr. Thakuria said. “If you really suspect MCC and you don’t get a result on your first biopsy, you may want to consider doing a second deeper biopsy, perhaps even a telescoping biopsy. This is especially true if your first biopsy was via shave technique and showed normal skin.”
• Refer to surgical oncology and radiation oncology ASAP. “You want to call them to ensure speedy consultation, within 1 week if possible,” she said. “Remember that all clinically node-negative MCCs warrant consideration of sentinel lymph node biopsy, regardless of tumor size. Upstaging will occur in 25%-32% of patients.”

Staging workup includes a full skin and lymph node exam to identify in-transit metastases and regional lymphadenopathy. “Palpation is key,” Dr. Thakuria said. “Next, you want to do some form of radiographic examination, so either a scalp to toes PET/CT or CT scan of the chest, abdomen, and pelvis. Finally, sentinel lymph node biopsy is going to be important if you have a clinically node-negative patient but you want to pathologically stage the person appropriately.” Although not formally part of the staging workup, she recommends ordering an AMERK test at diagnosis. AMERK detects antibodies to a Merkel cell polyomavirus oncoprotein, which is a marker of disease status present in about half of MCC patients. It falls with the treatment of cancer and rises with recurrence.

Discussing prognosis with MCC patients “can be challenging and uncomfortable, but even more so if you’re unfamiliar with some of the nuances of the terminology that is used,” Dr. Thakuria said. “Patients who go to Google are often going to encounter overall survival numbers, which are going to be worse than disease-specific numbers in any disease because they take into account death from any cause. This effect is heightened in MCC because this is cancer of predominately older adults, so there are other competing causes of death in this population, which drags down the overall survival estimates.”

Another point to remember when discussing survival with patients is that advances in immunotherapy are not necessarily reflected in national databases. “This is important, because usually in any cancer there’s a 5- to 10-year lag in survival information,” she said. “The last 5 years have brought an incredible change to MCC because of the advent of immunotherapy. Now we’re seeing incredible responses [in the clinic], but we’re not yet seeing those reflected in our survival tables.”

According to an analysis of prognostic factors from 9,387 MCC cases, nodal status is one of most important predictors of lower survival at 5 years, compared with having local disease: 35% versus 51%, respectively. Among patients with macroscopic lymph nodes, having known primary disease is associated with a lower survival at 5 years, compared with having unknown primary disease (27% vs. 42% at five years).

Dr. Thakuria concluded her presentation by recommending a three-step plan for surveillance, starting with a full skin and lymph node exam every 3-6 months for the first 3 years and every 6-12 months thereafter. Second, she advised routine imaging for high risk patients (American Joint Committee on Cancer stage 2 and above) and symptom-directed imaging for low-risk patients. Finally, she recommended the AMERK test every 3 months for the first 2-3 years in patients who were seropositive at diagnosis. A rising titer may be an early indicator of recurrence.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Thakuria reported having no financial disclosures.
 

[email protected]