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Mortality from cancer has dropped substantially in the United States over the past 5 decades, according to a new analysis.

Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.

The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.

“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.

Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.

The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.

The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.

“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.

Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.

In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”

However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.

The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.

“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Mortality from cancer has dropped substantially in the United States over the past 5 decades, according to a new analysis.

Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.

The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.

“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.

Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.

The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.

The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.

“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.

Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.

In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”

However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.

The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.

“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Mortality from cancer has dropped substantially in the United States over the past 5 decades, according to a new analysis.

Researchers found that rates for all cancers combined declined by 27% overall between 1971 and 2019 and decreased significantly for 12 of the 15 top cancer sites analyzed.

The data revealed even greater mortality declines for certain cancers in particular years. For example, mortality from lung cancer was 44% lower in 2019, compared with its peak rate in 1993, whereas it was only 13% lower, compared with morality rates in 1971.

“The cancer mortality rate has reduced considerably since 1971 overall and for most cancer sites because of improvements in prevention, early detection, and treatment,” lead author Ahmedin Jemal, DVM, PhD, American Cancer Society, Kennesaw, Ga., and colleagues wrote.

Advances in surgery, radiotherapy, chemotherapy, precision medicine, and combinations therapies over the past 5 decades have contributed to these significant declines in mortality, Dr. Jemal and colleagues explained. The researchers also credit the “expanded investment” in the National Cancer Institute’s annual budget following the 1971 National Cancer Act, which increased the budget 25-fold from $227 million in 1971 to $6 billion in 2019.

The report, published online Nov. 11, 2021, in JAMA Oncology, analyzed mortality rates for all cancers as well as the top 15 sites using the National Center for Health Statistics.

The researchers found that, overall, deaths declined significantly for all cancers over the study period. Some of the biggest headway since 1971 occurred for stomach and cervical cancers – with 72% and 69% lower mortality rates, respectively – as well as colorectal cancer (56%), oral cavity and pharynx cancer (43%), and ovarian cancer (41%). Mortality rates of female breast cancer and prostate cancer also dropped considerably – both by 39%.

“The decline in mortality for female breast, cervical, colorectal, and prostate cancer in part reflects increased detection (and removal) of premalignant lesions and early-stage cancers,” Dr. Jemal and colleagues noted.

Data suggest that screening likely explains about half of the observed decline in mortality from colorectal cancer between 1975 and 2002. A 2018 study also found that the use of adjuvant chemotherapy was responsible for 63% of the decline in mortality from female breast cancer between 2000 and 2012.

In addition, the authors noted, “the decline in lung, oral cavity and bladder cancers largely reflects reductions in smoking because of enhanced public awareness of the health consequences, implementation of increased cigarette excise taxes, and comprehensive smoke-free laws.”

However, mortality did increase in a few categories. For instance, the mortality rate from pancreatic cancer increased by 3% between 1971 and 2019, and by 8% for both esophageal and brain cancers. Mortality rates from cancer were also greater for 29% of the U.S. counties included in the analysis, mostly those in the South.

The increase in mortality from pancreatic cancer likely reflects the growing rates of obesity in the United States, along with no real advances in pancreatic cancer prevention, early detection, or treatment, the authors suggested. In addition, lack of progress in regions of the south may be related to unequal access to improvements in treatment compared with other parts of the country.

“Improving equity through investment in the social determinants of health and implementation research is critical to furthering the national cancer-control agenda,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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

The death rate from Parkinson’s disease has increased by about 63% over the past 2 decades in the United States, according to what investigators say is the most comprehensive study in the nation of temporal trends in Parkinson’s disease mortality.

“The reason behind the rising death rates from Parkinson’s disease is not clear at present and warrants further investigation,” Wei Bao, MD, PhD, associate professor in the department of epidemiology at the University of Iowa College of Public Health, in Iowa City, said in an interview. “We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s disease,” Dr. Bao added in a statement.

“Understanding why more people are dying from this disease is critical if we are going to reverse the trend,” Dr. Bao said.

The study was published online Oct. 27 in Neurology.

Long-term data

The researchers used data from the National Vital Statistics System to determine national trends in Parkinson’s disease mortality overall and in several key subgroups. The analyses included 479,059 people who died of Parkinson’s disease between 1999 and 2019.

Over the 21-year period, the age-adjusted mortality from Parkinson’s disease rose from 5.4 per 100,000 in 1999 to 8.8 per 100,000 in 2019. The average annual percent change (APC) was 2.4% for the entire period.

During the study period, the number of deaths from Parkinson’s disease more than doubled, from 14,593 to 35,311.

The death rate from Parkinson’s disease increased significantly across all age groups. The average APC was 5.0% among adults younger than 65 years, 1.9% among those aged 65-74 years, 2.2% among those 75-84 years, and 2.7% among those 85 and older.

The death rate increased in both men and women, but age-adjusted Parkinson’s disease mortality was twice as high in men as in women. The researchers say one possible explanation for the sex difference is estrogen, which leads to higher dopamine levels in areas of the brain that control motor responses and may protect women from Parkinson’s disease.

The study also showed that White people are more likely to die from Parkinson’s disease than persons of other racial and ethnic groups. In 2019, the death rate per 100,000 was 9.7 for Whites, 6.5 for Hispanics, and 4.7 for non-Hispanic Blacks.

Previous studies have shown that compared with White people, Black and Hispanic people are less likely to see a neurologist, owing to socioeconomic barriers. This suggests that White people may be more likely to receive a Parkinson’s disease diagnosis, the researchers noted.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr. Bao said.

“This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy,” Dr. Bao added.
 

1.2 million patients by 2030

Reached for comment, James Beck, PhD, chief scientific officer for the Parkinson’s Foundation, said these findings are not surprising. “They are aligned with the work the Parkinson’s Foundation has done to show that the number of people with Parkinson’s disease has increased over time. We are working on an improved estimate of Parkinson’s disease incidence and predict that Parkinson’s disease will continue to rise as the population ages, so an increase in mortality rates would be expected,” Dr. Beck said.

He noted that much of the public health statistics regarding Parkinson’s disease are outdated and that the Parkinson’s Foundation has been partnering with others to update them.

“For instance, to calculate an accurate estimate of the prevalence of Parkinson’s disease, the Parkinson’s Foundation Prevalence Project was formed. The findings from this group demonstrated that the number of people living with Parkinson’s disease will rise to nearly 1.2 million by 2030, a substantial increase from the estimate of 930,000 for 2020,” Dr. Beck said.

“The overarching message is that more people are being diagnosed with Parkinson’s disease, not that more people are dying from the disease,” he added.

“Over the last 20 years, our understanding of Parkinson’s disease has changed and developed, so clinicians are more aware and better able to properly diagnose Parkinson’s disease. This could mean that the cause is likely due to an increase in diagnosis rates and better recognition of Parkinson’s disease, which would lead to higher rates of identifying Parkinson’s disease as a cause of death,” said Dr. Beck.

The study had no targeted funding. Dr. Bao and Dr. Beck have indicated no relevant financial relationships.
 

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

Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.

By comparison, revenues from other types of medications decreased by 18% during the same period.

“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.

To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.

The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.

Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.

Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.

Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.

“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

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

Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.

By comparison, revenues from other types of medications decreased by 18% during the same period.

“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.

To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.

The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.

Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.

Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.

Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.

“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

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

Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.

By comparison, revenues from other types of medications decreased by 18% during the same period.

“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.

To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.

The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.

Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.

Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.

Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.

“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”

No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.

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

A number of late-phase clinical trials in lymphoma and multiple myeloma (MM) have opened in recent months. Maybe one of your patients could benefit from being enrolled? 

Untreated peripheral T-cell lymphoma 

Adult patients with peripheral T-cell lymphoma who have received no therapy except corticosteroids are invited to join a phase 2 study testing duvelisib (Copiktra) added to usual chemotherapy. Duvelisib is currently used in relapsed/refractory patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or follicular lymphoma; this study explores first-line use in a different type of lymphoma, so it may be a potential new indication for the drug. All participants will receive a 5-month chemotherapy regimen of cyclophosphamide, doxorubicin (Adriamycin, Rubex), vincristine (Oncovin), prednisone, and etoposide (VePesid). One group will also take oral azacitidine (Vidaza) while the third (experimental) group has oral duvelisib. The primary outcome is complete remission rate; overall survival (OS) is a secondary outcome. Quality of life (QoL) is not measured apart from mood and fatigue. The study opened at Memorial Sloan Kettering Cancer Center on July 30 for up to 170 participants. 

Untreated CLL/SLL 

Patients with CLL/SLL, no 17p deletions, and no prior systemic therapy can join a phase 3 study of pirtobrutinib, an investigational oral tyrosine-kinase inhibitor. Pirtobrutinib targets Bruton's tyrosine kinase, an intracellular signaler that is crucial to the proliferation and survival of leukemic cells. The trial will involve treatment for up to 5 years, with either oral pirtobrutinib or a standard combination of intravenous bendamustine (Treakisym, Treanda, Ribomustin) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera). Investigators at the study site, the California Research Institute in Los Angeles, started recruiting on Sept. 23 hoping for 250 participants. Progression-free survival is the primary outcome, OS is a secondary measure, and QoL will not be tracked.  

Relapsed or refractory follicular lymphoma after one line of therapy

 Adult patients who have CD20-positive follicular lymphoma (grades 1-3A) who have received at least one prior systemic lymphoma therapy can join a phase 3 trial of investigational drug mosunetuzumab combined with lenalidomide (Revlimid, Linamide). Participants in the mosunetuzumab group will be treated with the drug combo for approximately 1 year then followed for 8 years. People in the comparator group will receive a rituximab-lenalidomide combination instead. The trial planned to start enrolling on Oct. 31, looking for a total of 400 people in 144 study locations worldwide, including in nine U.S. states. The primary outcome is progression-free survival. OS is a secondary outcome and, apart from fatigue, QoL parameters will not be assessed.  

Relapsed or refractory follicular lymphoma after two lines of therapy 

Adults with follicular lymphoma (grades 1-3A) despite two or more treatment regimens, including at least one anti-CD20 therapy, are eligible for a phase 2 study of loncastuximab tesirine (Zynlonta). The drug already has an FDA accelerated approval this year for a different lymphoma, relapsed/refractory large B-cell lymphoma, so this could be a new indication. In this trial, it will be compared with idelalisib (Zydelig), which is already approved for follicular lymphoma. Participants will get either an infusion of loncastuximab every 3 weeks or a twice-daily tablet of idelalisib for up to 30 months. Investigators started recruiting on Oct. 30 and hope for 150 participants in Nevada and New Jersey. Complete response rate is the primary outcome. OS and QoL are secondary outcome measures. 

Untreated multiple myeloma not eligible for autologous stem-cell transplant (ASCT) 

Adults with untreated multiple myeloma who are not eligible for stem-cell transplantation are sought for a phase 2 study testing the performance of selinexor (Xpovio) plus dexamethasone. (Prior treatment with emergency steroids and radiation therapy is allowed.) Selinexor plus dexamethasone was approved in 2019 for multiple myeloma after four prior therapies; the goal of this study is to assess its performance as frontline treatment. Participants will receive oral selinexor and dexamethasone for up to 3 years in addition to subcutaneous daratumumab (Darzalex) and capsules of lenalidomide. The study opened Sept. 10, aiming for 100 participants at sites in Arizona, Colorado, Maryland, New York, Oregon, Texas, and Virginia. OS is a secondary outcome measure; QoL will not be assessed.  

Newly diagnosed multiple myeloma where ASCT not planned 

Patients with newly diagnosed multiple myeloma who are not having ASCT as initial therapy are eligible for a phase 3 study of the investigational CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel). This product targets B-cell maturation antigen (BCMA), which is expressed on the surface of mature B lymphocytes and malignant plasma cells; it is in late-stage clinical trials for multiple myeloma but has not yet been approved. In this study, the control-group participants will receive standard therapy for up to approximately 4 years - a regimen of bortezomib (Velcade), lenalidomide, and dexamethasone. Patients destined for cilta-cel will undergo apheresis to garner their T cells, which will then be genetically engineered to express the synthetic antigen receptor, duplicated, and re-infused. During the 6-month wait between apheresis and the cilta-cel infusion, the CAR T patients will receive similar treatment to the control group. Recruitment started for 650 patients across 12 U.S. states and 24 countries on August 19. The primary outcome is progression-free survival. OS and QoL are secondary measures and will be tracked for approximately 12 years. 

All trial information is from the National Institutes of Health U.S. National Library of Medicine.

A version of this article first appeared on Medscape.com

A number of late-phase clinical trials in lymphoma and multiple myeloma (MM) have opened in recent months. Maybe one of your patients could benefit from being enrolled? 

Untreated peripheral T-cell lymphoma 

Adult patients with peripheral T-cell lymphoma who have received no therapy except corticosteroids are invited to join a phase 2 study testing duvelisib (Copiktra) added to usual chemotherapy. Duvelisib is currently used in relapsed/refractory patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or follicular lymphoma; this study explores first-line use in a different type of lymphoma, so it may be a potential new indication for the drug. All participants will receive a 5-month chemotherapy regimen of cyclophosphamide, doxorubicin (Adriamycin, Rubex), vincristine (Oncovin), prednisone, and etoposide (VePesid). One group will also take oral azacitidine (Vidaza) while the third (experimental) group has oral duvelisib. The primary outcome is complete remission rate; overall survival (OS) is a secondary outcome. Quality of life (QoL) is not measured apart from mood and fatigue. The study opened at Memorial Sloan Kettering Cancer Center on July 30 for up to 170 participants. 

Untreated CLL/SLL 

Patients with CLL/SLL, no 17p deletions, and no prior systemic therapy can join a phase 3 study of pirtobrutinib, an investigational oral tyrosine-kinase inhibitor. Pirtobrutinib targets Bruton's tyrosine kinase, an intracellular signaler that is crucial to the proliferation and survival of leukemic cells. The trial will involve treatment for up to 5 years, with either oral pirtobrutinib or a standard combination of intravenous bendamustine (Treakisym, Treanda, Ribomustin) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera). Investigators at the study site, the California Research Institute in Los Angeles, started recruiting on Sept. 23 hoping for 250 participants. Progression-free survival is the primary outcome, OS is a secondary measure, and QoL will not be tracked.  

Relapsed or refractory follicular lymphoma after one line of therapy

 Adult patients who have CD20-positive follicular lymphoma (grades 1-3A) who have received at least one prior systemic lymphoma therapy can join a phase 3 trial of investigational drug mosunetuzumab combined with lenalidomide (Revlimid, Linamide). Participants in the mosunetuzumab group will be treated with the drug combo for approximately 1 year then followed for 8 years. People in the comparator group will receive a rituximab-lenalidomide combination instead. The trial planned to start enrolling on Oct. 31, looking for a total of 400 people in 144 study locations worldwide, including in nine U.S. states. The primary outcome is progression-free survival. OS is a secondary outcome and, apart from fatigue, QoL parameters will not be assessed.  

Relapsed or refractory follicular lymphoma after two lines of therapy 

Adults with follicular lymphoma (grades 1-3A) despite two or more treatment regimens, including at least one anti-CD20 therapy, are eligible for a phase 2 study of loncastuximab tesirine (Zynlonta). The drug already has an FDA accelerated approval this year for a different lymphoma, relapsed/refractory large B-cell lymphoma, so this could be a new indication. In this trial, it will be compared with idelalisib (Zydelig), which is already approved for follicular lymphoma. Participants will get either an infusion of loncastuximab every 3 weeks or a twice-daily tablet of idelalisib for up to 30 months. Investigators started recruiting on Oct. 30 and hope for 150 participants in Nevada and New Jersey. Complete response rate is the primary outcome. OS and QoL are secondary outcome measures. 

Untreated multiple myeloma not eligible for autologous stem-cell transplant (ASCT) 

Adults with untreated multiple myeloma who are not eligible for stem-cell transplantation are sought for a phase 2 study testing the performance of selinexor (Xpovio) plus dexamethasone. (Prior treatment with emergency steroids and radiation therapy is allowed.) Selinexor plus dexamethasone was approved in 2019 for multiple myeloma after four prior therapies; the goal of this study is to assess its performance as frontline treatment. Participants will receive oral selinexor and dexamethasone for up to 3 years in addition to subcutaneous daratumumab (Darzalex) and capsules of lenalidomide. The study opened Sept. 10, aiming for 100 participants at sites in Arizona, Colorado, Maryland, New York, Oregon, Texas, and Virginia. OS is a secondary outcome measure; QoL will not be assessed.  

Newly diagnosed multiple myeloma where ASCT not planned 

Patients with newly diagnosed multiple myeloma who are not having ASCT as initial therapy are eligible for a phase 3 study of the investigational CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel). This product targets B-cell maturation antigen (BCMA), which is expressed on the surface of mature B lymphocytes and malignant plasma cells; it is in late-stage clinical trials for multiple myeloma but has not yet been approved. In this study, the control-group participants will receive standard therapy for up to approximately 4 years - a regimen of bortezomib (Velcade), lenalidomide, and dexamethasone. Patients destined for cilta-cel will undergo apheresis to garner their T cells, which will then be genetically engineered to express the synthetic antigen receptor, duplicated, and re-infused. During the 6-month wait between apheresis and the cilta-cel infusion, the CAR T patients will receive similar treatment to the control group. Recruitment started for 650 patients across 12 U.S. states and 24 countries on August 19. The primary outcome is progression-free survival. OS and QoL are secondary measures and will be tracked for approximately 12 years. 

All trial information is from the National Institutes of Health U.S. National Library of Medicine.

A version of this article first appeared on Medscape.com

A number of late-phase clinical trials in lymphoma and multiple myeloma (MM) have opened in recent months. Maybe one of your patients could benefit from being enrolled? 

Untreated peripheral T-cell lymphoma 

Adult patients with peripheral T-cell lymphoma who have received no therapy except corticosteroids are invited to join a phase 2 study testing duvelisib (Copiktra) added to usual chemotherapy. Duvelisib is currently used in relapsed/refractory patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or follicular lymphoma; this study explores first-line use in a different type of lymphoma, so it may be a potential new indication for the drug. All participants will receive a 5-month chemotherapy regimen of cyclophosphamide, doxorubicin (Adriamycin, Rubex), vincristine (Oncovin), prednisone, and etoposide (VePesid). One group will also take oral azacitidine (Vidaza) while the third (experimental) group has oral duvelisib. The primary outcome is complete remission rate; overall survival (OS) is a secondary outcome. Quality of life (QoL) is not measured apart from mood and fatigue. The study opened at Memorial Sloan Kettering Cancer Center on July 30 for up to 170 participants. 

Untreated CLL/SLL 

Patients with CLL/SLL, no 17p deletions, and no prior systemic therapy can join a phase 3 study of pirtobrutinib, an investigational oral tyrosine-kinase inhibitor. Pirtobrutinib targets Bruton's tyrosine kinase, an intracellular signaler that is crucial to the proliferation and survival of leukemic cells. The trial will involve treatment for up to 5 years, with either oral pirtobrutinib or a standard combination of intravenous bendamustine (Treakisym, Treanda, Ribomustin) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera). Investigators at the study site, the California Research Institute in Los Angeles, started recruiting on Sept. 23 hoping for 250 participants. Progression-free survival is the primary outcome, OS is a secondary measure, and QoL will not be tracked.  

Relapsed or refractory follicular lymphoma after one line of therapy

 Adult patients who have CD20-positive follicular lymphoma (grades 1-3A) who have received at least one prior systemic lymphoma therapy can join a phase 3 trial of investigational drug mosunetuzumab combined with lenalidomide (Revlimid, Linamide). Participants in the mosunetuzumab group will be treated with the drug combo for approximately 1 year then followed for 8 years. People in the comparator group will receive a rituximab-lenalidomide combination instead. The trial planned to start enrolling on Oct. 31, looking for a total of 400 people in 144 study locations worldwide, including in nine U.S. states. The primary outcome is progression-free survival. OS is a secondary outcome and, apart from fatigue, QoL parameters will not be assessed.  

Relapsed or refractory follicular lymphoma after two lines of therapy 

Adults with follicular lymphoma (grades 1-3A) despite two or more treatment regimens, including at least one anti-CD20 therapy, are eligible for a phase 2 study of loncastuximab tesirine (Zynlonta). The drug already has an FDA accelerated approval this year for a different lymphoma, relapsed/refractory large B-cell lymphoma, so this could be a new indication. In this trial, it will be compared with idelalisib (Zydelig), which is already approved for follicular lymphoma. Participants will get either an infusion of loncastuximab every 3 weeks or a twice-daily tablet of idelalisib for up to 30 months. Investigators started recruiting on Oct. 30 and hope for 150 participants in Nevada and New Jersey. Complete response rate is the primary outcome. OS and QoL are secondary outcome measures. 

Untreated multiple myeloma not eligible for autologous stem-cell transplant (ASCT) 

Adults with untreated multiple myeloma who are not eligible for stem-cell transplantation are sought for a phase 2 study testing the performance of selinexor (Xpovio) plus dexamethasone. (Prior treatment with emergency steroids and radiation therapy is allowed.) Selinexor plus dexamethasone was approved in 2019 for multiple myeloma after four prior therapies; the goal of this study is to assess its performance as frontline treatment. Participants will receive oral selinexor and dexamethasone for up to 3 years in addition to subcutaneous daratumumab (Darzalex) and capsules of lenalidomide. The study opened Sept. 10, aiming for 100 participants at sites in Arizona, Colorado, Maryland, New York, Oregon, Texas, and Virginia. OS is a secondary outcome measure; QoL will not be assessed.  

Newly diagnosed multiple myeloma where ASCT not planned 

Patients with newly diagnosed multiple myeloma who are not having ASCT as initial therapy are eligible for a phase 3 study of the investigational CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel). This product targets B-cell maturation antigen (BCMA), which is expressed on the surface of mature B lymphocytes and malignant plasma cells; it is in late-stage clinical trials for multiple myeloma but has not yet been approved. In this study, the control-group participants will receive standard therapy for up to approximately 4 years - a regimen of bortezomib (Velcade), lenalidomide, and dexamethasone. Patients destined for cilta-cel will undergo apheresis to garner their T cells, which will then be genetically engineered to express the synthetic antigen receptor, duplicated, and re-infused. During the 6-month wait between apheresis and the cilta-cel infusion, the CAR T patients will receive similar treatment to the control group. Recruitment started for 650 patients across 12 U.S. states and 24 countries on August 19. The primary outcome is progression-free survival. OS and QoL are secondary measures and will be tracked for approximately 12 years. 

All trial information is from the National Institutes of Health U.S. National Library of Medicine.

A version of this article first appeared on Medscape.com

It’s rare for mothers with COVID-19 to transfer the infection to their newborns, according to a new small study.

The research, published in JAMA Network Open, found that newborns of mothers infected with the COVID-19 virus were able to develop their own immune defenses via their mother’s breast milk. Researchers detected antibodies in the infants’ saliva.

“It is the first time that this mechanism has been demonstrated,” said study author Rita Carsetti, MD, head of immunology diagnostics for Bambino Gesù Children’s Hospital in Rome. “We now know how breast milk can help babies develop their immune defenses. The system could work the same way for many other pathogens, which are present in the mother during breastfeeding.”

Dr. Carsetti and colleagues examined data from 28 pregnant women who tested positive for COVID-19 and who gave birth at Policlinico Umberto I in Rome between November 2020 and May 2021, and their newborns. They investigated the immune responses of the mothers and their newborns by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breast milk and infant saliva 48 hours after delivery and 2 months later.

Twenty-one mothers and their newborns completed the 2 months of follow-up. Researchers found that the majority of the mothers had mild symptoms of COVID-19, while only three of them were admitted for worsening condition. There was only one reported case of a possible vertical transmission – transmitted in utero – and one case of a horizontal infection through droplets or respiratory secretions, which occurred when the newborn was taken home.

The results of the study showed that antibodies specific to the virus were present in the mothers’ blood at 2 months after delivery, but not at 48 hours. However, in milk, specific antibodies were already present 48 hours after delivery.

Therefore, after 48 hours, the breastfed babies had specific mucosal antibodies against COVID-19 in their saliva that the other newborns did not have. Two months later, these antibodies continued to be present even though the mothers had stopped producing them.

The findings suggest that breast milk offers protection by transferring the antibodies produced by the mother to the baby, but also by helping them to produce their own immune defenses.

“I am not surprised that infants of mothers who had COVID-19 infection in the peripartum period pass anti-spike protein IgA to their infants,” J. Howard Smart, MD, FAAP, who was not involved with the study, said in an interview. “This confirmation is good news for breastfeeding mothers.

“I wonder whether we really know these infants did not become infected, and produce their own antibodies,” said Dr. Smart, chairman of the department of pediatrics at Sharp Rees-Stealy Medical Group in San Diego.

The American College of Obstetricians and Gynecologists said having COVID-19 should not stop mothers from giving their children breast milk. The organization also said that the chance of COVID-19 passing through the breast milk and causing infection in the newborn infant is slim.

“Breast milk also helps protect babies from infections, including infections of the ears, lungs, and digestive system. For these reasons, having COVID-19 should not stop you from giving your baby breast milk,” according to ACOG’s website.

Similar studies on mothers who received the COVID-19 vaccination rather than being infected would be interesting, Dr. Smart added.

The authors of the current study plan to broaden their research by evaluating the response of pregnant mothers vaccinated against SARS-CoV-2 for the presence of antibodies in the milk and the immunity of their newborns. Dr. Carsetti said her team plans to expand the study to other infections, such as cytomegalovirus and respiratory syncytial virus.

None of the researchers or commentators had financial disclosures.

It’s rare for mothers with COVID-19 to transfer the infection to their newborns, according to a new small study.

The research, published in JAMA Network Open, found that newborns of mothers infected with the COVID-19 virus were able to develop their own immune defenses via their mother’s breast milk. Researchers detected antibodies in the infants’ saliva.

“It is the first time that this mechanism has been demonstrated,” said study author Rita Carsetti, MD, head of immunology diagnostics for Bambino Gesù Children’s Hospital in Rome. “We now know how breast milk can help babies develop their immune defenses. The system could work the same way for many other pathogens, which are present in the mother during breastfeeding.”

Dr. Carsetti and colleagues examined data from 28 pregnant women who tested positive for COVID-19 and who gave birth at Policlinico Umberto I in Rome between November 2020 and May 2021, and their newborns. They investigated the immune responses of the mothers and their newborns by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breast milk and infant saliva 48 hours after delivery and 2 months later.

Twenty-one mothers and their newborns completed the 2 months of follow-up. Researchers found that the majority of the mothers had mild symptoms of COVID-19, while only three of them were admitted for worsening condition. There was only one reported case of a possible vertical transmission – transmitted in utero – and one case of a horizontal infection through droplets or respiratory secretions, which occurred when the newborn was taken home.

The results of the study showed that antibodies specific to the virus were present in the mothers’ blood at 2 months after delivery, but not at 48 hours. However, in milk, specific antibodies were already present 48 hours after delivery.

Therefore, after 48 hours, the breastfed babies had specific mucosal antibodies against COVID-19 in their saliva that the other newborns did not have. Two months later, these antibodies continued to be present even though the mothers had stopped producing them.

The findings suggest that breast milk offers protection by transferring the antibodies produced by the mother to the baby, but also by helping them to produce their own immune defenses.

“I am not surprised that infants of mothers who had COVID-19 infection in the peripartum period pass anti-spike protein IgA to their infants,” J. Howard Smart, MD, FAAP, who was not involved with the study, said in an interview. “This confirmation is good news for breastfeeding mothers.

“I wonder whether we really know these infants did not become infected, and produce their own antibodies,” said Dr. Smart, chairman of the department of pediatrics at Sharp Rees-Stealy Medical Group in San Diego.

The American College of Obstetricians and Gynecologists said having COVID-19 should not stop mothers from giving their children breast milk. The organization also said that the chance of COVID-19 passing through the breast milk and causing infection in the newborn infant is slim.

“Breast milk also helps protect babies from infections, including infections of the ears, lungs, and digestive system. For these reasons, having COVID-19 should not stop you from giving your baby breast milk,” according to ACOG’s website.

Similar studies on mothers who received the COVID-19 vaccination rather than being infected would be interesting, Dr. Smart added.

The authors of the current study plan to broaden their research by evaluating the response of pregnant mothers vaccinated against SARS-CoV-2 for the presence of antibodies in the milk and the immunity of their newborns. Dr. Carsetti said her team plans to expand the study to other infections, such as cytomegalovirus and respiratory syncytial virus.

None of the researchers or commentators had financial disclosures.

It’s rare for mothers with COVID-19 to transfer the infection to their newborns, according to a new small study.

The research, published in JAMA Network Open, found that newborns of mothers infected with the COVID-19 virus were able to develop their own immune defenses via their mother’s breast milk. Researchers detected antibodies in the infants’ saliva.

“It is the first time that this mechanism has been demonstrated,” said study author Rita Carsetti, MD, head of immunology diagnostics for Bambino Gesù Children’s Hospital in Rome. “We now know how breast milk can help babies develop their immune defenses. The system could work the same way for many other pathogens, which are present in the mother during breastfeeding.”

Dr. Carsetti and colleagues examined data from 28 pregnant women who tested positive for COVID-19 and who gave birth at Policlinico Umberto I in Rome between November 2020 and May 2021, and their newborns. They investigated the immune responses of the mothers and their newborns by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breast milk and infant saliva 48 hours after delivery and 2 months later.

Twenty-one mothers and their newborns completed the 2 months of follow-up. Researchers found that the majority of the mothers had mild symptoms of COVID-19, while only three of them were admitted for worsening condition. There was only one reported case of a possible vertical transmission – transmitted in utero – and one case of a horizontal infection through droplets or respiratory secretions, which occurred when the newborn was taken home.

The results of the study showed that antibodies specific to the virus were present in the mothers’ blood at 2 months after delivery, but not at 48 hours. However, in milk, specific antibodies were already present 48 hours after delivery.

Therefore, after 48 hours, the breastfed babies had specific mucosal antibodies against COVID-19 in their saliva that the other newborns did not have. Two months later, these antibodies continued to be present even though the mothers had stopped producing them.

The findings suggest that breast milk offers protection by transferring the antibodies produced by the mother to the baby, but also by helping them to produce their own immune defenses.

“I am not surprised that infants of mothers who had COVID-19 infection in the peripartum period pass anti-spike protein IgA to their infants,” J. Howard Smart, MD, FAAP, who was not involved with the study, said in an interview. “This confirmation is good news for breastfeeding mothers.

“I wonder whether we really know these infants did not become infected, and produce their own antibodies,” said Dr. Smart, chairman of the department of pediatrics at Sharp Rees-Stealy Medical Group in San Diego.

The American College of Obstetricians and Gynecologists said having COVID-19 should not stop mothers from giving their children breast milk. The organization also said that the chance of COVID-19 passing through the breast milk and causing infection in the newborn infant is slim.

“Breast milk also helps protect babies from infections, including infections of the ears, lungs, and digestive system. For these reasons, having COVID-19 should not stop you from giving your baby breast milk,” according to ACOG’s website.

Similar studies on mothers who received the COVID-19 vaccination rather than being infected would be interesting, Dr. Smart added.

The authors of the current study plan to broaden their research by evaluating the response of pregnant mothers vaccinated against SARS-CoV-2 for the presence of antibodies in the milk and the immunity of their newborns. Dr. Carsetti said her team plans to expand the study to other infections, such as cytomegalovirus and respiratory syncytial virus.

None of the researchers or commentators had financial disclosures.

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

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

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

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

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

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

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

LAS VEGAS – People with obesity may be able to reduce their risk of colorectal cancer with weight loss surgery or medication, researchers say.

“We need to have conversations with our patients in the clinic and educate them that they have these resources available,” said Aakash Desai, MD, a hospitalist at MetroHealth Medical Center, Cleveland, in an interview with this news organization.

Dr. Desai and colleagues found that sleeve gastrectomy and four medications were associated with a reduced risk of colorectal cancer but Roux-en-Y gastrojejunostomy and orlistat were not.

Coauthor Zryan Shwani, MD, a gastroenterology fellow at Sibley Memorial Hospital, Washington, D.C., presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

Working with an underserved population with high rates of obesity in northeastern Ohio, the researchers wondered how surgery and medication could affect these patients.

They analyzed data from the IBM Explorys clinical database, which compiles and standardizes data from electronic medical records on about 74 million patients from more than 300 U.S. hospitals. Consistent with previous studies, they determined that patients with obesity in the database were 2.5 times more likely than people with a healthy weight to be diagnosed with colorectal cancer (odds ratio, 2.48; 95% CI, 2.45-2.51).

Zeroing in on people who had weight loss interventions, they included adults aged 18-75 years who had undergone either Roux-en-Y gastrojejunostomy or sleeve gastrectomy, or had taken the medications liraglutide, orlistat, phentermine/topiramate, bupropion/naltrexone, or lorcaserin.

They excluded patients with Lynch syndrome, intestinal polyposis syndrome, a family history of gastrointestinal malignancy, inflammatory bowel disease, or tobacco or alcohol abuse. Patients who had taken one of the weight loss medications and also had type 2 diabetes were excluded. They did not include patients who had undergone gastric banding because it has become less popular.

For the weight loss medication group, they found 117,730 patients who met their criteria. For the surgery group, 43,050 patients met the criteria.

In analyzing the colorectal cancer rates, they included only diagnoses of malignant neoplasms made 2 years after the interventions.

They compared these patients to a control group of 52,540 people matched in age, with a body mass index (BMI) greater than 30 kg/m² who did not undergo weight loss surgery or take weight loss medication.

Among the 9,370 patients who underwent Roux-en-Y gastrojejunostomy, 50 were diagnosed with colorectal cancer and 400 had benign polyps. Their rate of colorectal cancer was not statistically different from people who didn’t have surgery (OR, 1.09; 95% CI, 0.82-1.43). The rate of benign polyps after Roux-en-Y gastrojejunostomy was greater (OR, 1.72; 95% CI, 1.55-1.90).

On the other hand, among the 33,680 patients who underwent sleeve gastrectomy, 50 were diagnosed with colorectal cancer, a lower rate than in the population who didn’t have surgery (OR, 0.30; 95% CI, 0.22-0.39). Their risk of benign polyps was also reduced (OR, 0.45; 95% CI, 0.40-0.50).

All of the medications were significantly associated with a lower risk of colorectal cancer, except orlistat (OR, 0.94; 95% CI, 0.72-1.25).

The finding on Roux-en-Y gastrojejunostomy agreed with studies from England and Nordic countries showing double the risk of colorectal cancer in those patients but conflicted with a French study showing decreased risk, Dr. Shwani said.

While the study doesn’t establish a reason why Roux-en-Y gastrojejunostomy was less beneficial, other researchers have associated the procedure with biomarkers of inflammation, Dr. Shwani said. “It’s inconsistent, and I don’t think we have a clear answer why.”

As a retrospective analysis, the study could not establish a cause-and-effect relationship between surgery or medication and cancer, or adjust for such factors as diet, exercise, or genes, he acknowledged.

Colorectal cancer is just one outcome to consider when deciding whether to undergo weight loss surgery or take weight loss drugs, said session moderator Mohammad Yaghoobi, MD, an associate professor of medicine at McMaster University, Hamilton, Ont.

“The most important outcome that should be investigated is the survival of the patients after obesity surgery,” he told this news organization. “The second would be the quality of life of those patients. Colon cancer is preventable if you are having regular colonoscopies.”

Other studies have not shown much difference between patients who have weight loss surgery and those who don’t, he added.

The study was funded by Merck. Dr. Desai and Dr. Shwani have reported receiving grant funding from Merck. Dr. Yaghoobi has reported no relevant financial relationships.

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

Stereotactic body radiation therapy (SBRT) directed at progressive lesions in patients with oligoprogressive metastatic non–small cell lung cancer (NSCLC) was beneficial and significantly improved progression-free survival (PFS), suggest clinical trial results presented this week.

Patients treated with SBRT had a median PFS of 44 weeks, compared with 9 weeks for those who received standard care.

However, no benefit was observed in patients with metastatic breast cancer. There was no significant difference in PFS between the two groups (18 weeks with SBRT vs. 19 weeks with standard care).

“In this preplanned interim analysis, we demonstrated the benefit of SBRT to sites of oligoprogression on overall progression-free survival, which was the primary endpoint,” said lead author C. Jillian Tsai, MD, PhD, a radiation oncologist and director of metastatic disease radiation oncology research at Memorial Sloan Kettering Cancer Center in New York. “The difference was driven by the substantial response in [this] NSCLC cohort.”

There was no benefit of SBRT seen in the breast cohort, she noted, and most breast patients developed new lesions upon further progression.

Dr. Tsai and colleagues are planning to close the trial early, after the interim analysis established the benefit of SBRT. They are now investigating why SBRT was beneficial in NSCLC but not in breast cancer.

The findings were presented at the American Society for Radiation Oncology (ASTRO) annual meeting.

Dr. Tsai explained that the current standard of care for patients with oligoprogressive metastatic NSCLC is to switch to a different targeted therapy or chemotherapy following progression, but options may be limited. Efficacy for second-line therapy can be poor, with PFS ranging from about 4 months to 10 months for NSCLC, “and after second line, efficacy for third and fourth lines is even poorer,” she said.

Similarly, for breast cancer, PFS ranges from about 9 months to 20 months for estrogen-receptor positive patients. “But for triple negative patients, there really is no standard of care and PFS is poor,” Dr. Tsai said.
 

SBRT superior to standard of care

The authors hypothesized that there is an oligoprogressive state in metastatic cancer, in which disease control can be improved by applying local therapy to progressive lesions only.

The cohort included 102 patients with metastatic NSCLC or breast cancer who had received one or more lines of systemic therapy and had oligoprogressive lesions amenable to SBRT. There was no upper limit of nonprogressive lesions.

Oligoprogression was defined as Response Evaluation or Positron Emission Tomography Response Criteria in Solid Tumors documented progression ≤5 individual lesions.

Patients were randomly assigned to receive either SBRT to all progressive sites plus palliative standard of care or systemic SOC only. Systemic therapy was per physician’s discretion.

There were 58 patients with NSCLC (30 in the SBRT group) and 44 patients with breast cancer (22 in each group).

Most patients (75%) had more than one site of oligoprogression and 47% had more than 5 total metastatic lesions. About half of patients (54%) had received immunotherapy and the majority of those with NSCLC (86%) did not harbor an actionable driver mutation. About one-third (32%) of the breast cancer cohort were triple negative.

Patients were followed for a median of 45 weeks (58 weeks for living patients), by which time 78 (74%) had experienced further tumor progression and 39 (37%) had died.

Median progression-free survival for the entire cohort was 31 weeks for SBRT and 11 weeks for palliative SOC (P = .002).

In multivariable analysis that stratified for factors including age, sex, lines of systemic therapy, and change of systemic therapy, the progression-free survival benefit of SBRT continued to remain substantial in the NSCLC cohort (hazard ratio: 0.38; P = .007).

Adverse events were higher in the SBRT group. Grade 2 or higher adverse events occurred in 23 (61%) of SBRT patients, and 15 (40%) of SOC patients (P = .13).
 

Hoped-for results, with a few caveats

Approached for comment on the new findings, Clifford Robinson, MD, professor of radiation oncology, chief of SBRT service, and director of clinical trials and informatics at Washington University, St. Louis, said the results tie in with previous findings.

There are multiple published or presented prospective randomized phase 2 and 3 trials in various disease sites that have explored the role of local therapy, including SBRT, for patients who present with oligometastatic disease.

“These studies have nearly uniformly shown improvements in progression-free and/or overall survival with the inclusion of local therapy,” he told this news organization. Dr. Robinson was not involved with the study.

He explained that relatively few patients present with oligometastatic disease. However, many patients present with more advanced disease, but after an initial course of systemic therapy, develop oligoprogression.

“There is tremendous appeal to using local therapy at the time of oligoprogression in lieu of switching systemic therapy,” said Dr. Robinson. “It allows patients to stay on systemic therapy that is otherwise effective for the remainder of their disease.”

First-line systemic therapies are the most effective and the most tolerable, he continued, and switching systemic therapy introduces the potential for more toxicity and less efficacy. Therefore, it has become increasingly popular to offer SBRT to one or a few sites of oligoprogressive disease based on the results of oligometastatic disease.

“However, there is no established prospective data to guide this practice,” he said. “This trial is the first to examine this carefully in lung and breast cancer patients, and this trial shows what we hoped to see – that use of SBRT after oligoprogression results in improved progression-free survival as compared with standard of care alone. And this was accomplished with limited toxicity.”

There are a few caveats, though, he pointed out. “Progression-free survival is defined as time to first progression or death,” he said. “Since we don’t know what the overall survival is in this abstract, it’s entirely possible that patients live for the same length of time, but just take longer to progress.”

Another caveat is that this was a planned interim analysis. “Typically, planned interim analyses occur to see if the trial should be stopped or to adjust the study based on results,” he said. “It’s unclear what the investigators will do with this information.”

“But overall, these are very exciting data and lend support to the increasingly common practice of treating oligoprogressive disease,” Dr. Robinson added. “Since most of the serious adverse events of SBRT occur later, longer follow-up is needed, although the median survival of patients may not reach that timepoint.”

“For now, practice should not be altered based on these interim results,” he added.

Dr. Tsai reported acting as a consultant/advisor for Varian and Galera and also receiving research funding from Varian. Dr. Robinson reports stock/ownership in Radialogica, acting as a consultant/advisor for Varian, AstraZeneca, EMD Serono, Quantitative Radiology Solutions, research funding from Varian and Merck, and owning patents on systems for cardiac arrhythmias and ablation.

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

Stereotactic body radiation therapy (SBRT) directed at progressive lesions in patients with oligoprogressive metastatic non–small cell lung cancer (NSCLC) was beneficial and significantly improved progression-free survival (PFS), suggest clinical trial results presented this week.

Patients treated with SBRT had a median PFS of 44 weeks, compared with 9 weeks for those who received standard care.

However, no benefit was observed in patients with metastatic breast cancer. There was no significant difference in PFS between the two groups (18 weeks with SBRT vs. 19 weeks with standard care).

“In this preplanned interim analysis, we demonstrated the benefit of SBRT to sites of oligoprogression on overall progression-free survival, which was the primary endpoint,” said lead author C. Jillian Tsai, MD, PhD, a radiation oncologist and director of metastatic disease radiation oncology research at Memorial Sloan Kettering Cancer Center in New York. “The difference was driven by the substantial response in [this] NSCLC cohort.”

There was no benefit of SBRT seen in the breast cohort, she noted, and most breast patients developed new lesions upon further progression.

Dr. Tsai and colleagues are planning to close the trial early, after the interim analysis established the benefit of SBRT. They are now investigating why SBRT was beneficial in NSCLC but not in breast cancer.

The findings were presented at the American Society for Radiation Oncology (ASTRO) annual meeting.

Dr. Tsai explained that the current standard of care for patients with oligoprogressive metastatic NSCLC is to switch to a different targeted therapy or chemotherapy following progression, but options may be limited. Efficacy for second-line therapy can be poor, with PFS ranging from about 4 months to 10 months for NSCLC, “and after second line, efficacy for third and fourth lines is even poorer,” she said.

Similarly, for breast cancer, PFS ranges from about 9 months to 20 months for estrogen-receptor positive patients. “But for triple negative patients, there really is no standard of care and PFS is poor,” Dr. Tsai said.
 

SBRT superior to standard of care

The authors hypothesized that there is an oligoprogressive state in metastatic cancer, in which disease control can be improved by applying local therapy to progressive lesions only.

The cohort included 102 patients with metastatic NSCLC or breast cancer who had received one or more lines of systemic therapy and had oligoprogressive lesions amenable to SBRT. There was no upper limit of nonprogressive lesions.

Oligoprogression was defined as Response Evaluation or Positron Emission Tomography Response Criteria in Solid Tumors documented progression ≤5 individual lesions.

Patients were randomly assigned to receive either SBRT to all progressive sites plus palliative standard of care or systemic SOC only. Systemic therapy was per physician’s discretion.

There were 58 patients with NSCLC (30 in the SBRT group) and 44 patients with breast cancer (22 in each group).

Most patients (75%) had more than one site of oligoprogression and 47% had more than 5 total metastatic lesions. About half of patients (54%) had received immunotherapy and the majority of those with NSCLC (86%) did not harbor an actionable driver mutation. About one-third (32%) of the breast cancer cohort were triple negative.

Patients were followed for a median of 45 weeks (58 weeks for living patients), by which time 78 (74%) had experienced further tumor progression and 39 (37%) had died.

Median progression-free survival for the entire cohort was 31 weeks for SBRT and 11 weeks for palliative SOC (P = .002).

In multivariable analysis that stratified for factors including age, sex, lines of systemic therapy, and change of systemic therapy, the progression-free survival benefit of SBRT continued to remain substantial in the NSCLC cohort (hazard ratio: 0.38; P = .007).

Adverse events were higher in the SBRT group. Grade 2 or higher adverse events occurred in 23 (61%) of SBRT patients, and 15 (40%) of SOC patients (P = .13).
 

Hoped-for results, with a few caveats

Approached for comment on the new findings, Clifford Robinson, MD, professor of radiation oncology, chief of SBRT service, and director of clinical trials and informatics at Washington University, St. Louis, said the results tie in with previous findings.

There are multiple published or presented prospective randomized phase 2 and 3 trials in various disease sites that have explored the role of local therapy, including SBRT, for patients who present with oligometastatic disease.

“These studies have nearly uniformly shown improvements in progression-free and/or overall survival with the inclusion of local therapy,” he told this news organization. Dr. Robinson was not involved with the study.

He explained that relatively few patients present with oligometastatic disease. However, many patients present with more advanced disease, but after an initial course of systemic therapy, develop oligoprogression.

“There is tremendous appeal to using local therapy at the time of oligoprogression in lieu of switching systemic therapy,” said Dr. Robinson. “It allows patients to stay on systemic therapy that is otherwise effective for the remainder of their disease.”

First-line systemic therapies are the most effective and the most tolerable, he continued, and switching systemic therapy introduces the potential for more toxicity and less efficacy. Therefore, it has become increasingly popular to offer SBRT to one or a few sites of oligoprogressive disease based on the results of oligometastatic disease.

“However, there is no established prospective data to guide this practice,” he said. “This trial is the first to examine this carefully in lung and breast cancer patients, and this trial shows what we hoped to see – that use of SBRT after oligoprogression results in improved progression-free survival as compared with standard of care alone. And this was accomplished with limited toxicity.”

There are a few caveats, though, he pointed out. “Progression-free survival is defined as time to first progression or death,” he said. “Since we don’t know what the overall survival is in this abstract, it’s entirely possible that patients live for the same length of time, but just take longer to progress.”

Another caveat is that this was a planned interim analysis. “Typically, planned interim analyses occur to see if the trial should be stopped or to adjust the study based on results,” he said. “It’s unclear what the investigators will do with this information.”

“But overall, these are very exciting data and lend support to the increasingly common practice of treating oligoprogressive disease,” Dr. Robinson added. “Since most of the serious adverse events of SBRT occur later, longer follow-up is needed, although the median survival of patients may not reach that timepoint.”

“For now, practice should not be altered based on these interim results,” he added.

Dr. Tsai reported acting as a consultant/advisor for Varian and Galera and also receiving research funding from Varian. Dr. Robinson reports stock/ownership in Radialogica, acting as a consultant/advisor for Varian, AstraZeneca, EMD Serono, Quantitative Radiology Solutions, research funding from Varian and Merck, and owning patents on systems for cardiac arrhythmias and ablation.

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

Stereotactic body radiation therapy (SBRT) directed at progressive lesions in patients with oligoprogressive metastatic non–small cell lung cancer (NSCLC) was beneficial and significantly improved progression-free survival (PFS), suggest clinical trial results presented this week.

Patients treated with SBRT had a median PFS of 44 weeks, compared with 9 weeks for those who received standard care.

However, no benefit was observed in patients with metastatic breast cancer. There was no significant difference in PFS between the two groups (18 weeks with SBRT vs. 19 weeks with standard care).

“In this preplanned interim analysis, we demonstrated the benefit of SBRT to sites of oligoprogression on overall progression-free survival, which was the primary endpoint,” said lead author C. Jillian Tsai, MD, PhD, a radiation oncologist and director of metastatic disease radiation oncology research at Memorial Sloan Kettering Cancer Center in New York. “The difference was driven by the substantial response in [this] NSCLC cohort.”

There was no benefit of SBRT seen in the breast cohort, she noted, and most breast patients developed new lesions upon further progression.

Dr. Tsai and colleagues are planning to close the trial early, after the interim analysis established the benefit of SBRT. They are now investigating why SBRT was beneficial in NSCLC but not in breast cancer.

The findings were presented at the American Society for Radiation Oncology (ASTRO) annual meeting.

Dr. Tsai explained that the current standard of care for patients with oligoprogressive metastatic NSCLC is to switch to a different targeted therapy or chemotherapy following progression, but options may be limited. Efficacy for second-line therapy can be poor, with PFS ranging from about 4 months to 10 months for NSCLC, “and after second line, efficacy for third and fourth lines is even poorer,” she said.

Similarly, for breast cancer, PFS ranges from about 9 months to 20 months for estrogen-receptor positive patients. “But for triple negative patients, there really is no standard of care and PFS is poor,” Dr. Tsai said.
 

SBRT superior to standard of care

The authors hypothesized that there is an oligoprogressive state in metastatic cancer, in which disease control can be improved by applying local therapy to progressive lesions only.

The cohort included 102 patients with metastatic NSCLC or breast cancer who had received one or more lines of systemic therapy and had oligoprogressive lesions amenable to SBRT. There was no upper limit of nonprogressive lesions.

Oligoprogression was defined as Response Evaluation or Positron Emission Tomography Response Criteria in Solid Tumors documented progression ≤5 individual lesions.

Patients were randomly assigned to receive either SBRT to all progressive sites plus palliative standard of care or systemic SOC only. Systemic therapy was per physician’s discretion.

There were 58 patients with NSCLC (30 in the SBRT group) and 44 patients with breast cancer (22 in each group).

Most patients (75%) had more than one site of oligoprogression and 47% had more than 5 total metastatic lesions. About half of patients (54%) had received immunotherapy and the majority of those with NSCLC (86%) did not harbor an actionable driver mutation. About one-third (32%) of the breast cancer cohort were triple negative.

Patients were followed for a median of 45 weeks (58 weeks for living patients), by which time 78 (74%) had experienced further tumor progression and 39 (37%) had died.

Median progression-free survival for the entire cohort was 31 weeks for SBRT and 11 weeks for palliative SOC (P = .002).

In multivariable analysis that stratified for factors including age, sex, lines of systemic therapy, and change of systemic therapy, the progression-free survival benefit of SBRT continued to remain substantial in the NSCLC cohort (hazard ratio: 0.38; P = .007).

Adverse events were higher in the SBRT group. Grade 2 or higher adverse events occurred in 23 (61%) of SBRT patients, and 15 (40%) of SOC patients (P = .13).
 

Hoped-for results, with a few caveats

Approached for comment on the new findings, Clifford Robinson, MD, professor of radiation oncology, chief of SBRT service, and director of clinical trials and informatics at Washington University, St. Louis, said the results tie in with previous findings.

There are multiple published or presented prospective randomized phase 2 and 3 trials in various disease sites that have explored the role of local therapy, including SBRT, for patients who present with oligometastatic disease.

“These studies have nearly uniformly shown improvements in progression-free and/or overall survival with the inclusion of local therapy,” he told this news organization. Dr. Robinson was not involved with the study.

He explained that relatively few patients present with oligometastatic disease. However, many patients present with more advanced disease, but after an initial course of systemic therapy, develop oligoprogression.

“There is tremendous appeal to using local therapy at the time of oligoprogression in lieu of switching systemic therapy,” said Dr. Robinson. “It allows patients to stay on systemic therapy that is otherwise effective for the remainder of their disease.”

First-line systemic therapies are the most effective and the most tolerable, he continued, and switching systemic therapy introduces the potential for more toxicity and less efficacy. Therefore, it has become increasingly popular to offer SBRT to one or a few sites of oligoprogressive disease based on the results of oligometastatic disease.

“However, there is no established prospective data to guide this practice,” he said. “This trial is the first to examine this carefully in lung and breast cancer patients, and this trial shows what we hoped to see – that use of SBRT after oligoprogression results in improved progression-free survival as compared with standard of care alone. And this was accomplished with limited toxicity.”

There are a few caveats, though, he pointed out. “Progression-free survival is defined as time to first progression or death,” he said. “Since we don’t know what the overall survival is in this abstract, it’s entirely possible that patients live for the same length of time, but just take longer to progress.”

Another caveat is that this was a planned interim analysis. “Typically, planned interim analyses occur to see if the trial should be stopped or to adjust the study based on results,” he said. “It’s unclear what the investigators will do with this information.”

“But overall, these are very exciting data and lend support to the increasingly common practice of treating oligoprogressive disease,” Dr. Robinson added. “Since most of the serious adverse events of SBRT occur later, longer follow-up is needed, although the median survival of patients may not reach that timepoint.”

“For now, practice should not be altered based on these interim results,” he added.

Dr. Tsai reported acting as a consultant/advisor for Varian and Galera and also receiving research funding from Varian. Dr. Robinson reports stock/ownership in Radialogica, acting as a consultant/advisor for Varian, AstraZeneca, EMD Serono, Quantitative Radiology Solutions, research funding from Varian and Merck, and owning patents on systems for cardiac arrhythmias and ablation.

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

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com

Mary Lou McMaster, MD, has spent her entire career at the National Cancer Institute (NCI) searching for the genetic underpinnings that give rise to Waldenstrom's macroglobulinemia (WM). 
After searching for decades, she has yet to uncover a "smoking gun," though a few tantalizing clues have emerged along the way. 
"Our questions are pretty basic: Why are some people more susceptible to developing WM, and why does WM sometimes cluster in families?" she explained. It turns out that the answers are not at all simple. 
Dr. McMaster described some of the clues that her team at the Clinical Genetics Branch of the NCI has unearthed in a presentation at the recent International Waldenstrom's Macroglobulinemia Foundation (IWMF) 2021 Virtual Educational Forum. 
Commenting after the presentation, Steven Treon, MD, PhD, professor of medicine, Harvard Medical School, Boston, who is collaborating with Dr. McMaster on this work, said: "From these familial studies, we can learn how familial genomics may give us insights into disease prevention and treatment." 

Identifying affected families  

Work began in 2001 to identify families in which two or more family members had been diagnosed with WM or in which there was one patient with WM and at least one other relative with a related B-cell cancer, such as chronic lymphocytic leukemia. 
For a frame of reference, they enrolled some families with only one member with WM and in which there was no known family history of the disease. 
"Overall, we have learned that familial WM is a rare disease but not nearly as rare as we first thought," Dr. McMaster said. 
For example, in a referral hospital setting, 5% of WM patients will report having a family member with the same disorder, and up to 20% of WM patients report having a family member with a related but different B-cell cancer, she noted. 
NCI researchers also discovered that environmental factors contribute to the development of WM. Notable chemical or occupational exposures include exposures to pesticides, herbicides, and fertilizers. Infections and autoimmune disease are additional factors. 
"This was not a surprise," Dr. McMaster commented regarding the role of occupational exposures. The research community has known for decades that a "lymphoma belt" cuts through the Midwest farming states. 
Focusing on genetic susceptibility, Dr. McMaster and colleagues first tried to identify a rare germline variant that can be passed down to offspring and that might confer high risk for the disease. 
"We used our high-risk families to study these types of changes, although they may be modified by other genes and environmental factors," Dr. McMaster explained. 
Much to their collective disappointment, the research team has been unable to identify any rare germline variant that could account for WM in many families. What they did find were many small changes in genes that are known to be important in B-cell development and function, but all of those would lead to only a small increase in WM risk. 
"What is holding us back is that, so far, we are not seeing the same gene affected in more than one family, so this suggests to us either that this is not the mechanism behind the development of WM in families, or we have an unfortunate situation where each family is going to have a genetic change that is private to that family and which is not found in other families," Dr. McMaster acknowledged. 

Sheer difficulty  

Given the difficulty of determining whether these small genetic changes had any detrimental functional effect in each and every family with a member who had WM, Dr. McMaster and colleagues have now turned their attention to genes that exert only a small effect on disease risk. 
"Here, we focused on specific genes that we knew were important in the function of the immune system," she explained. "We did find a few genes that may contribute to risk, but those have not yet been confirmed by us or others, and we cannot say they are causative without that confirmation," she said. 
The team has gone on to scan the highway of our genetic material so as to isolate genetic "mile markers." They then examine the area around a particular marker that they suspect contains genes that may be involved in WM. 
One study they conducted involved a cohort of 217 patients with WM in which numerous family members had WM and so was enriched with susceptibility genes. A second cohort comprised 312 WM patients in which there were few WM cases among family members. Both of these cohorts were compared with a group of healthy control persons. 
From these genome studies, "we found there are at least two regions of the genome that can contribute to WM susceptibility, the largest effect being on the short arm of chromosome 6, and the other on the long arm of chromosome 14," Dr. McMaster reported. Dr. McMaster feels that there are probably more regions on the genome that also contribute to WM, although they do not yet understand how these regions contribute to susceptibility. 
"It's more evidence that WM likely results from a combination of events rather than one single gene variant," she observed. Dr. McMaster and colleagues are now collaborating with a large consortium of WM researchers to confirm and extend their findings. Plans are underway to analyze data from approximately 1,350 WM patients and more than 20,000 control persons within the next year. 
"Our hope is that we will confirm our original findings and, because we now have a much larger sample, we will be able to discover additional regions of the genome that are contributing to susceptibility," Dr. McMaster said. 
"A single gene is not likely to account for all WM, as we've looked carefully and others have looked too," she commented. 
"So the risk for WM depends on a combination of genes and environmental exposures and possibly lifestyle factors as well, although we still estimate that approximately 25% of the heritability of WM can be attributed to these kinds of genetic changes," Dr. McMaster predicted. 
Dr. McMaster has disclosed no relevant financial relationships. Dr. Treon has served as a director, officer, partner, employee, advisor, consultant, or trustee for Janssen, Pfizer, PCYC, and BioGene.  

A version of this article first appeared on Medscape.com