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Should you quit employment to open a practice? These docs share how they did it
“Everyone said private practice is dying,” said Omar Maniya, MD, an emergency physician who left his hospital job for family practice in New Jersey. “But I think it could be one of the best models we have to advance our health care system and prevent burnout – and bring joy back to the practice of medicine.”
But employment doesn’t necessarily mean happiness. In the Medscape “Employed Physicians: Loving the Focus, Hating the Bureaucracy” ” report, more than 1,350 U.S. physicians employed by a health care organization, hospital, large group practice, or other medical group were surveyedabout their work. As the subtitle suggests, many are torn.
In the survey, employed doctors cited three main downsides to the lifestyle: They have less autonomy, more corporate rules than they’d like, and lower earning potential. Nearly one-third say they’re unhappy about their work-life balance, too, which raises the risk for burnout.
Some physicians find that employment has more cons than pros and turn to private practice instead.
A system skewed toward employment
In the mid-1990s, when James Milford, MD, completed his residency, going straight into private practice was the norm. The family physician bucked that trend by joining a large regional medical center in Wisconsin. He spent the next 20+ years working to establish a network of medical clinics.
“It was very satisfying,” Dr. Milford said. “When I started, I had a lot of input, a lot of control.”
Since then, the pendulum has been swinging toward employment. Brieanna Seefeldt, DO, a family physician outside Denver, completed her residency in 2012.
“I told the recruiter I wanted my own practice,” Dr. Seefeldt said, “They said if you’re not independently wealthy, there’s no way.”
Sonal G. Patel, MD, a pediatric neurologist in Bethesda, finished her residency the same year as Dr. Seefeldt. Dr. Patel never even considered private practice.
“I always thought I would have a certain amount of clinic time where I have my regular patients,” she said, “but I’d also be doing hospital rounds and reading EEG studies at the hospital.”
For Dr. Maniya, who completed his residency in 2021, the choice was simple. Growing up, he watched his immigrant parents, both doctors in private practice, struggle to keep up.
“I opted for a big, sophisticated health system,” he said. “I thought we’d be pushing the envelope of what was possible in medicine.”
Becoming disillusioned with employment
All four of these physicians are now in private practice and are much happier.
Within a few years of starting her job, Dr. Seefeldt was one of the top producers in her area but felt tremendous pressure to see more and more patients. The last straw came after an unpaid maternity leave.
“They told me I owed them for my maternity leave, for lack of productivity,” she said. “I was in practice for only 4 years, but already feeling the effects of burnout.”
Dr. Patel only lasted 2 years before realizing employment didn’t suit her.
“There was an excessive amount of hospital calls,” she said. “And there were bureaucratic issues that made it very difficult to practice the way I thought my practice would be.”
It took just 18 months for Dr. Maniya’s light-bulb moment. He was working at a hospital when COVID-19 hit.
“At my big health care system, it took 9 months to come up with a way to get COVID swabs for free,” he said. “At the same time, I was helping out the family business, a private practice. It took me two calls and 48 hours to get free swabs for not just the practice, not just our patients, but the entire city of Hamilton, New Jersey.”
Milford lasted the longest as an employee – nearly 25 years. The end came after a healthcare company with hospitals in 30 states bought out the medical center.
“My control gradually eroded,” he said. “It got to the point where I had no input regarding things like employees or processes we wanted to improve.”
Making the leap to private practice
Private practice can take different forms.
Dr. Seefeldt opted for direct primary care, a model in which her patients pay a set monthly fee for care whenever needed. Her practice doesn’t take any insurance besides Medicaid.
“Direct primary care is about working directly with the patient and cost-conscious, transparent care,” she said. “And I don’t have to deal with insurance.”
For Dr. Patel, working with an accountable care organization made the transition easier. She owns her practice solo but works with a company called Privia for administrative needs. Privia sent a consultant to set up her office in the company’s electronic medical record. Things were up and running within the first week.
Dr. Maniya joined his mother’s practice, easing his way in over 18 months.
And then there’s what Milford did, building a private practice from the ground up.
“We did a lot of Googling, a lot of meeting with accountants, meeting with small business development from the state of Wisconsin,” he said. “We asked people that were in business, ‘What are the things businesses fail on? Not medical practices, but businesses.’” All that research helped him launch successfully.
Making the dollars and cents add up
Moving from employment into private practice takes time, effort, and of course, money. How much of each varies depending on where you live, your specialty, whether you choose to rent or buy office space, staffing needs, and other factors.
Dr. Seefeldt, Dr. Patel, Dr. Milford, and Dr. Maniya illustrate the range.
- Dr. Seefeldt got a home equity loan of $50,000 to cover startup costs – and paid it back within 6 months.
- Purchasing EEG equipment added to Dr. Patel’s budget; she spent $130,000 of her own money to launch her practice in a temporary office and took out a $150,000 loan to finance the buildout of her final space. It took her 3 years to pay it back.
- When Dr. Milford left employment, he borrowed the buildout and startup costs for his practice from his father, a retired surgeon, to the tune of $500,000.
- Dr. Maniya assumed the largest risk. When he took over the family practice, he borrowed $1.5 million to modernize and build a new office. The practice has now quintupled in size. “It’s going great,” he said. “One of our questions is, should we pay back the loan at a faster pace rather than make the minimum payments?”
Several years in, Dr. Patel reports she’s easily making three to four times as much as she would have at a hospital. However, Dr. Maniya’s guaranteed compensation is 10% less than his old job.
“But as a partner in a private practice, if it succeeds, it could be 100%-150% more in a good year,” he said. On the flip side, if the practice runs into financial trouble, so does he. “Does the risk keep me up at night, give me heartburn? You betcha.”
Dr. Milford and Dr. Seefeldt have both chosen to take less compensation than they could, opting to reinvest in and nurture their practices.
“I love it,” said Dr. Milford. “I joke that I have half as much in my pocketbook, twice as much in my heart. But it’s not really half as much, 5 years in. If I weren’t growing the business, I’d be making more than before.”
Private practice is not without challenges
Being the big cheese does have drawbacks. In the current climate, staffing is a persistent issue for doctors in private practice – both maintaining a full staff and managing their employees.
And without the backing of a large corporation, doctors are sometimes called on to do less than pleasant tasks.
“If the toilet gets clogged and the plumber can’t come for a few hours, the patients still need a bathroom,” Dr. Maniya said. “I’ll go in with my $400 shoes and snake the toilet.”
Dr. Milford pointed out that when the buck stops with you, small mistakes can have enormous ramifications. “But with the bad comes the great potential for good. You have the ability to positively affect patients and healthcare, and to make a difference for people. It creates great personal satisfaction.”
Is running your own practice all it’s cracked up to be?
If it’s not yet apparent, all four doctors highly recommend moving from employment to private practice when possible. The autonomy and the improved work-life balance have helped them find the satisfaction they’d been missing while making burnout less likely.
“When you don’t have to spend 30% of your day apologizing to patients for how bad the health care system is, it reignites your passion for why you went into medicine in the first place,” said Dr. Maniya. In his practice, he’s made a conscious decision to pursue a mix of demographics. “Thirty percent of our patients are Medicaid. The vast majority are middle to low income.”
For physicians who are also parents, the ability to set their own schedules is life-changing.
“My son got an award ... and the teacher invited me to the assembly. In a corporate-based world, I’d struggle to be able to go,” said Dr. Seefeldt. As her own boss, she didn’t have to forgo this special event. Instead, she coordinated directly with her scheduled patient to make time for it.
In Medscape’s report, 61% of employed physicians indicated that they don’t have a say on key management decisions. However, doctors who launch private practices embrace the chance to set their own standards.
“We make sure from the minute someone calls they know they’re in good hands, we’re responsive, we address concerns right away. That’s the difference with private practice – the one-on-one connection is huge,” said Dr. Patel.
“This is exactly what I always wanted. It brings me joy knowing we’ve made a difference in these children’s lives, in their parents’ lives,” she concluded.
A version of this article first appeared on Medscape.com.
“Everyone said private practice is dying,” said Omar Maniya, MD, an emergency physician who left his hospital job for family practice in New Jersey. “But I think it could be one of the best models we have to advance our health care system and prevent burnout – and bring joy back to the practice of medicine.”
But employment doesn’t necessarily mean happiness. In the Medscape “Employed Physicians: Loving the Focus, Hating the Bureaucracy” ” report, more than 1,350 U.S. physicians employed by a health care organization, hospital, large group practice, or other medical group were surveyedabout their work. As the subtitle suggests, many are torn.
In the survey, employed doctors cited three main downsides to the lifestyle: They have less autonomy, more corporate rules than they’d like, and lower earning potential. Nearly one-third say they’re unhappy about their work-life balance, too, which raises the risk for burnout.
Some physicians find that employment has more cons than pros and turn to private practice instead.
A system skewed toward employment
In the mid-1990s, when James Milford, MD, completed his residency, going straight into private practice was the norm. The family physician bucked that trend by joining a large regional medical center in Wisconsin. He spent the next 20+ years working to establish a network of medical clinics.
“It was very satisfying,” Dr. Milford said. “When I started, I had a lot of input, a lot of control.”
Since then, the pendulum has been swinging toward employment. Brieanna Seefeldt, DO, a family physician outside Denver, completed her residency in 2012.
“I told the recruiter I wanted my own practice,” Dr. Seefeldt said, “They said if you’re not independently wealthy, there’s no way.”
Sonal G. Patel, MD, a pediatric neurologist in Bethesda, finished her residency the same year as Dr. Seefeldt. Dr. Patel never even considered private practice.
“I always thought I would have a certain amount of clinic time where I have my regular patients,” she said, “but I’d also be doing hospital rounds and reading EEG studies at the hospital.”
For Dr. Maniya, who completed his residency in 2021, the choice was simple. Growing up, he watched his immigrant parents, both doctors in private practice, struggle to keep up.
“I opted for a big, sophisticated health system,” he said. “I thought we’d be pushing the envelope of what was possible in medicine.”
Becoming disillusioned with employment
All four of these physicians are now in private practice and are much happier.
Within a few years of starting her job, Dr. Seefeldt was one of the top producers in her area but felt tremendous pressure to see more and more patients. The last straw came after an unpaid maternity leave.
“They told me I owed them for my maternity leave, for lack of productivity,” she said. “I was in practice for only 4 years, but already feeling the effects of burnout.”
Dr. Patel only lasted 2 years before realizing employment didn’t suit her.
“There was an excessive amount of hospital calls,” she said. “And there were bureaucratic issues that made it very difficult to practice the way I thought my practice would be.”
It took just 18 months for Dr. Maniya’s light-bulb moment. He was working at a hospital when COVID-19 hit.
“At my big health care system, it took 9 months to come up with a way to get COVID swabs for free,” he said. “At the same time, I was helping out the family business, a private practice. It took me two calls and 48 hours to get free swabs for not just the practice, not just our patients, but the entire city of Hamilton, New Jersey.”
Milford lasted the longest as an employee – nearly 25 years. The end came after a healthcare company with hospitals in 30 states bought out the medical center.
“My control gradually eroded,” he said. “It got to the point where I had no input regarding things like employees or processes we wanted to improve.”
Making the leap to private practice
Private practice can take different forms.
Dr. Seefeldt opted for direct primary care, a model in which her patients pay a set monthly fee for care whenever needed. Her practice doesn’t take any insurance besides Medicaid.
“Direct primary care is about working directly with the patient and cost-conscious, transparent care,” she said. “And I don’t have to deal with insurance.”
For Dr. Patel, working with an accountable care organization made the transition easier. She owns her practice solo but works with a company called Privia for administrative needs. Privia sent a consultant to set up her office in the company’s electronic medical record. Things were up and running within the first week.
Dr. Maniya joined his mother’s practice, easing his way in over 18 months.
And then there’s what Milford did, building a private practice from the ground up.
“We did a lot of Googling, a lot of meeting with accountants, meeting with small business development from the state of Wisconsin,” he said. “We asked people that were in business, ‘What are the things businesses fail on? Not medical practices, but businesses.’” All that research helped him launch successfully.
Making the dollars and cents add up
Moving from employment into private practice takes time, effort, and of course, money. How much of each varies depending on where you live, your specialty, whether you choose to rent or buy office space, staffing needs, and other factors.
Dr. Seefeldt, Dr. Patel, Dr. Milford, and Dr. Maniya illustrate the range.
- Dr. Seefeldt got a home equity loan of $50,000 to cover startup costs – and paid it back within 6 months.
- Purchasing EEG equipment added to Dr. Patel’s budget; she spent $130,000 of her own money to launch her practice in a temporary office and took out a $150,000 loan to finance the buildout of her final space. It took her 3 years to pay it back.
- When Dr. Milford left employment, he borrowed the buildout and startup costs for his practice from his father, a retired surgeon, to the tune of $500,000.
- Dr. Maniya assumed the largest risk. When he took over the family practice, he borrowed $1.5 million to modernize and build a new office. The practice has now quintupled in size. “It’s going great,” he said. “One of our questions is, should we pay back the loan at a faster pace rather than make the minimum payments?”
Several years in, Dr. Patel reports she’s easily making three to four times as much as she would have at a hospital. However, Dr. Maniya’s guaranteed compensation is 10% less than his old job.
“But as a partner in a private practice, if it succeeds, it could be 100%-150% more in a good year,” he said. On the flip side, if the practice runs into financial trouble, so does he. “Does the risk keep me up at night, give me heartburn? You betcha.”
Dr. Milford and Dr. Seefeldt have both chosen to take less compensation than they could, opting to reinvest in and nurture their practices.
“I love it,” said Dr. Milford. “I joke that I have half as much in my pocketbook, twice as much in my heart. But it’s not really half as much, 5 years in. If I weren’t growing the business, I’d be making more than before.”
Private practice is not without challenges
Being the big cheese does have drawbacks. In the current climate, staffing is a persistent issue for doctors in private practice – both maintaining a full staff and managing their employees.
And without the backing of a large corporation, doctors are sometimes called on to do less than pleasant tasks.
“If the toilet gets clogged and the plumber can’t come for a few hours, the patients still need a bathroom,” Dr. Maniya said. “I’ll go in with my $400 shoes and snake the toilet.”
Dr. Milford pointed out that when the buck stops with you, small mistakes can have enormous ramifications. “But with the bad comes the great potential for good. You have the ability to positively affect patients and healthcare, and to make a difference for people. It creates great personal satisfaction.”
Is running your own practice all it’s cracked up to be?
If it’s not yet apparent, all four doctors highly recommend moving from employment to private practice when possible. The autonomy and the improved work-life balance have helped them find the satisfaction they’d been missing while making burnout less likely.
“When you don’t have to spend 30% of your day apologizing to patients for how bad the health care system is, it reignites your passion for why you went into medicine in the first place,” said Dr. Maniya. In his practice, he’s made a conscious decision to pursue a mix of demographics. “Thirty percent of our patients are Medicaid. The vast majority are middle to low income.”
For physicians who are also parents, the ability to set their own schedules is life-changing.
“My son got an award ... and the teacher invited me to the assembly. In a corporate-based world, I’d struggle to be able to go,” said Dr. Seefeldt. As her own boss, she didn’t have to forgo this special event. Instead, she coordinated directly with her scheduled patient to make time for it.
In Medscape’s report, 61% of employed physicians indicated that they don’t have a say on key management decisions. However, doctors who launch private practices embrace the chance to set their own standards.
“We make sure from the minute someone calls they know they’re in good hands, we’re responsive, we address concerns right away. That’s the difference with private practice – the one-on-one connection is huge,” said Dr. Patel.
“This is exactly what I always wanted. It brings me joy knowing we’ve made a difference in these children’s lives, in their parents’ lives,” she concluded.
A version of this article first appeared on Medscape.com.
“Everyone said private practice is dying,” said Omar Maniya, MD, an emergency physician who left his hospital job for family practice in New Jersey. “But I think it could be one of the best models we have to advance our health care system and prevent burnout – and bring joy back to the practice of medicine.”
But employment doesn’t necessarily mean happiness. In the Medscape “Employed Physicians: Loving the Focus, Hating the Bureaucracy” ” report, more than 1,350 U.S. physicians employed by a health care organization, hospital, large group practice, or other medical group were surveyedabout their work. As the subtitle suggests, many are torn.
In the survey, employed doctors cited three main downsides to the lifestyle: They have less autonomy, more corporate rules than they’d like, and lower earning potential. Nearly one-third say they’re unhappy about their work-life balance, too, which raises the risk for burnout.
Some physicians find that employment has more cons than pros and turn to private practice instead.
A system skewed toward employment
In the mid-1990s, when James Milford, MD, completed his residency, going straight into private practice was the norm. The family physician bucked that trend by joining a large regional medical center in Wisconsin. He spent the next 20+ years working to establish a network of medical clinics.
“It was very satisfying,” Dr. Milford said. “When I started, I had a lot of input, a lot of control.”
Since then, the pendulum has been swinging toward employment. Brieanna Seefeldt, DO, a family physician outside Denver, completed her residency in 2012.
“I told the recruiter I wanted my own practice,” Dr. Seefeldt said, “They said if you’re not independently wealthy, there’s no way.”
Sonal G. Patel, MD, a pediatric neurologist in Bethesda, finished her residency the same year as Dr. Seefeldt. Dr. Patel never even considered private practice.
“I always thought I would have a certain amount of clinic time where I have my regular patients,” she said, “but I’d also be doing hospital rounds and reading EEG studies at the hospital.”
For Dr. Maniya, who completed his residency in 2021, the choice was simple. Growing up, he watched his immigrant parents, both doctors in private practice, struggle to keep up.
“I opted for a big, sophisticated health system,” he said. “I thought we’d be pushing the envelope of what was possible in medicine.”
Becoming disillusioned with employment
All four of these physicians are now in private practice and are much happier.
Within a few years of starting her job, Dr. Seefeldt was one of the top producers in her area but felt tremendous pressure to see more and more patients. The last straw came after an unpaid maternity leave.
“They told me I owed them for my maternity leave, for lack of productivity,” she said. “I was in practice for only 4 years, but already feeling the effects of burnout.”
Dr. Patel only lasted 2 years before realizing employment didn’t suit her.
“There was an excessive amount of hospital calls,” she said. “And there were bureaucratic issues that made it very difficult to practice the way I thought my practice would be.”
It took just 18 months for Dr. Maniya’s light-bulb moment. He was working at a hospital when COVID-19 hit.
“At my big health care system, it took 9 months to come up with a way to get COVID swabs for free,” he said. “At the same time, I was helping out the family business, a private practice. It took me two calls and 48 hours to get free swabs for not just the practice, not just our patients, but the entire city of Hamilton, New Jersey.”
Milford lasted the longest as an employee – nearly 25 years. The end came after a healthcare company with hospitals in 30 states bought out the medical center.
“My control gradually eroded,” he said. “It got to the point where I had no input regarding things like employees or processes we wanted to improve.”
Making the leap to private practice
Private practice can take different forms.
Dr. Seefeldt opted for direct primary care, a model in which her patients pay a set monthly fee for care whenever needed. Her practice doesn’t take any insurance besides Medicaid.
“Direct primary care is about working directly with the patient and cost-conscious, transparent care,” she said. “And I don’t have to deal with insurance.”
For Dr. Patel, working with an accountable care organization made the transition easier. She owns her practice solo but works with a company called Privia for administrative needs. Privia sent a consultant to set up her office in the company’s electronic medical record. Things were up and running within the first week.
Dr. Maniya joined his mother’s practice, easing his way in over 18 months.
And then there’s what Milford did, building a private practice from the ground up.
“We did a lot of Googling, a lot of meeting with accountants, meeting with small business development from the state of Wisconsin,” he said. “We asked people that were in business, ‘What are the things businesses fail on? Not medical practices, but businesses.’” All that research helped him launch successfully.
Making the dollars and cents add up
Moving from employment into private practice takes time, effort, and of course, money. How much of each varies depending on where you live, your specialty, whether you choose to rent or buy office space, staffing needs, and other factors.
Dr. Seefeldt, Dr. Patel, Dr. Milford, and Dr. Maniya illustrate the range.
- Dr. Seefeldt got a home equity loan of $50,000 to cover startup costs – and paid it back within 6 months.
- Purchasing EEG equipment added to Dr. Patel’s budget; she spent $130,000 of her own money to launch her practice in a temporary office and took out a $150,000 loan to finance the buildout of her final space. It took her 3 years to pay it back.
- When Dr. Milford left employment, he borrowed the buildout and startup costs for his practice from his father, a retired surgeon, to the tune of $500,000.
- Dr. Maniya assumed the largest risk. When he took over the family practice, he borrowed $1.5 million to modernize and build a new office. The practice has now quintupled in size. “It’s going great,” he said. “One of our questions is, should we pay back the loan at a faster pace rather than make the minimum payments?”
Several years in, Dr. Patel reports she’s easily making three to four times as much as she would have at a hospital. However, Dr. Maniya’s guaranteed compensation is 10% less than his old job.
“But as a partner in a private practice, if it succeeds, it could be 100%-150% more in a good year,” he said. On the flip side, if the practice runs into financial trouble, so does he. “Does the risk keep me up at night, give me heartburn? You betcha.”
Dr. Milford and Dr. Seefeldt have both chosen to take less compensation than they could, opting to reinvest in and nurture their practices.
“I love it,” said Dr. Milford. “I joke that I have half as much in my pocketbook, twice as much in my heart. But it’s not really half as much, 5 years in. If I weren’t growing the business, I’d be making more than before.”
Private practice is not without challenges
Being the big cheese does have drawbacks. In the current climate, staffing is a persistent issue for doctors in private practice – both maintaining a full staff and managing their employees.
And without the backing of a large corporation, doctors are sometimes called on to do less than pleasant tasks.
“If the toilet gets clogged and the plumber can’t come for a few hours, the patients still need a bathroom,” Dr. Maniya said. “I’ll go in with my $400 shoes and snake the toilet.”
Dr. Milford pointed out that when the buck stops with you, small mistakes can have enormous ramifications. “But with the bad comes the great potential for good. You have the ability to positively affect patients and healthcare, and to make a difference for people. It creates great personal satisfaction.”
Is running your own practice all it’s cracked up to be?
If it’s not yet apparent, all four doctors highly recommend moving from employment to private practice when possible. The autonomy and the improved work-life balance have helped them find the satisfaction they’d been missing while making burnout less likely.
“When you don’t have to spend 30% of your day apologizing to patients for how bad the health care system is, it reignites your passion for why you went into medicine in the first place,” said Dr. Maniya. In his practice, he’s made a conscious decision to pursue a mix of demographics. “Thirty percent of our patients are Medicaid. The vast majority are middle to low income.”
For physicians who are also parents, the ability to set their own schedules is life-changing.
“My son got an award ... and the teacher invited me to the assembly. In a corporate-based world, I’d struggle to be able to go,” said Dr. Seefeldt. As her own boss, she didn’t have to forgo this special event. Instead, she coordinated directly with her scheduled patient to make time for it.
In Medscape’s report, 61% of employed physicians indicated that they don’t have a say on key management decisions. However, doctors who launch private practices embrace the chance to set their own standards.
“We make sure from the minute someone calls they know they’re in good hands, we’re responsive, we address concerns right away. That’s the difference with private practice – the one-on-one connection is huge,” said Dr. Patel.
“This is exactly what I always wanted. It brings me joy knowing we’ve made a difference in these children’s lives, in their parents’ lives,” she concluded.
A version of this article first appeared on Medscape.com.
Steep cost of surviving childhood HL: Epigenetic aging
AT ASH 2022 NEW ORLEANS
The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.
The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.
In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.
“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”
Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.
“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.
“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.
“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”
Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.
Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”
She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
Long-term complications
Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.
In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.
The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.
The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.
All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.
Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.
As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).
More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.
HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).
In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.
HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.
The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.
Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”
The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.
The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022 NEW ORLEANS
The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.
The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.
In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.
“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”
Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.
“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.
“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.
“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”
Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.
Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”
She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
Long-term complications
Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.
In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.
The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.
The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.
All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.
Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.
As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).
More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.
HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).
In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.
HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.
The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.
Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”
The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.
The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022 NEW ORLEANS
The research findings emerged from a study of nearly 500 individuals in their late 30s, of whom 215 were adult survivors of pediatric Hodgkin lymphoma (HL) and 282 were community controls.
The results showed that HL survivors had a higher epigenetic age relative to their chronological age, compared with controls, translating into epigenetic age acceleration over chronological age equivalent to a mean of 7.7 years.
In addition, this accelerated epigenetic aging in HL survivors was accompanied by neurocognitive deficits, including declines in visual-motor processing, short-term memory, verbal learning and recall, and executive function.
“We found that biologic aging is associated with long-term neurocognitive impairment in Hodgkin lymphoma survivors,” commented lead author AnnaLynn M. Williams, PhD, of the Wilmot Cancer Institute at the University of Rochester (N.Y.) “Specifically, we see strong and consistent associations with memory impairment, which suggests that biologic aging is likely related to cognitive aging.”
Dr. Williams presented the findings at the annual meeting of the American Society of Hematology.
“Our hope is that this biomarker may help us identify those survivors most at risk for early-onset cognitive aging and might actually help us gauge a preclinical response to interventions, so that we can see efficacy sooner than some other endpoints,” she said in a media briefing prior to presenting the data.
“This is an area that is very near and dear to my heart,” commented ASH President Jane N. Winter, MD, from Northwestern University, Chicago.
“Pediatricians have been very much wedded to very intensive therapies and intend to incorporate radiation more frequently in their treatment strategies for children than we do in adults,” she said. In addition, “we are very much focused on the long-term consequences of mediastinal radiation causing breast cancer in adults who were treated as young adults or children for Hodgkin lymphoma, but now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated.”
Such HL therapies may exert a significant long-term impact on a patient population “that we otherwise cure,” Dr. Winter commented, pointing to a study by investigators in Germany that showed high unemployment levels among adult survivors of childhood HL, compared with the general population.
Also reacting to Dr. Williams’ findings, Catherine Bollard, MD, of the Center for Cancer and Immunology Research at Children’s National Research Institute in Washington, D.C., said: “My concern actually is that even today, in pediatrics, we’re still giving combined chemotherapy and radiation to the majority of the children with the more advanced disease, and that is not what is happening for the treatment of adult Hodgkin disease.”
She noted that there are now many immune-based therapies available for Hodgkin lymphoma that could soon obviate the need for chemotherapy.
Long-term complications
Dr. Williams and colleagues had previously reported that, compared with their healthy siblings, long-term survivors of HL had significantly higher risk (P < .05 for all comparisons) of neurocognitive impairment, anxiety, depression, unemployment, and impaired physical/mental quality of life.
In the current study, they looked specifically at epigenetic aging, and asked all participants to complete a comprehensive neuropsychological battery of tests.
The 215 trial participants who were survivors of pediatric HL came from the St Jude Lifetime Cohort. The mean patient age was 39, and the survivors were an average of 25 years out from their initial diagnosis.
The mean age of the 282 community controls was 36 years. Both the cohort and the controls were all European ancestry.
All participants provided a blood sample. The investigators performed genome-wide methylation studies on DNA derived from peripheral blood mononuclear cells (PBMC), and used the data to calculate epigenetic age according to a biomarker called DNAm PhenoAge. Also known as “Levine’s Clock,” this epigenetic biomarker of aging for life span and health span was developed by Morgan E. Levine, PhD, and colleagues at the University of California, Los Angeles, and other centers.
Dr. Williams and her team determined epigenetic age acceleration by calculating the difference between epigenetic and chronological age, with a higher epigenetic accelerated age suggesting an older biological age relative to the patient’s actual age.
As noted above, they found that HL survivors had a significantly higher epigenetic accelerated age, compared with controls, equivalent to a mean difference of 7.7 years (P < .001).
More than 80% of the survivors had some degree of accelerated aging, compared with only 23% of controls.
HL survivors with higher degrees (second and third tertiles) of accelerated aging had significantly worse visual-motor processing speed compared with survivors in the first (lowest) tertile, with survivors in the second tertile performing on average 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 SD worse (P < .001).
In addition, relative to first tertile survivors, those in the second and third tertiles performed worse on short-term memory, with a decrease of –0.42 SD (P = .011) and 0.59 SD (P < .001), respectively.
HL survivors in the third tertile performed worse than those in the other tertiles on measures of verbal learning (P =.007) and long-term verbal recall (P = .005), and those in the second or third tertiles had an average decline of 0.4 SD, compared with those in first tertile on verbal fluency, a measure of executive function.
The declines in neurocognitive measures among survivors were relatively small but clinically significant, Dr. Williams said, and were likely to prove troublesome for patients.
Dr. Williams added that she and her colleagues are currently compiling data on a comparison of neurocognitive scores between cohort members and control, for future publication, “but I can say that, in the majority of measures that are reported on, survivors do worse.”
The investigators are planning expansion of DNA methylation profiling in the St. Jude Lifetime Cohort and will follow survivors prospectively to look for changes in epigenetic acceleration and how those changes might predict who is most at risk for neurocognitive decline.
The study was supported by grants from the National Cancer Institute. Dr. Williams, Dr. Winter, and Dr. Bollard all reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Alloantibody registry would save lives, money
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – Save lives; save money. What’s not to love? That’s the claim made for a proposed nationwide data bank on alloantibodies, which develop in response to foreign red blood cells in individuals who undergo repeated blood transfusions. They can occur after pregnancy or transplants, as well as in patients with sickle cell disease.
“The findings from our model are pretty definitive,” said George Goshua, MD, MSc, of Yale University, New Haven, Conn. “Despite very conservative assumptions, our results still show a huge financial benefit to having a system in place to serve as a preventive net that catches patients before they have to go through a delayed hemolytic transfusion reaction (DHTR).”
Dr. Goshua presented the study at the American Society of Hematology annual meeting. The proposed registry would significantly reduce the risk that transfusion-dependent patients, and others who require occasional transfusions, would develop complications requiring hospitalization, he said.
A similar registry has been up and running in the Netherlands for 15 years, he said at a press briefing.
Briefing moderator Catherine Bollard, MD, of the Center for Cancer and Immunology at Children’s National Research Institute in Washington, asked Dr. Goshua why such an exchange hasn’t been started in the United States already.
“I will say first that our European colleagues are far ahead in terms of preventative care,” he replied.
“On top of that, there’s a unique environment in the United States – and this dates back about 15 years now – where we are almost allergic to putting costs on benefits, that is, attaching a cost value to a benefit that a population can gain,” Dr. Goshua said. “So in this context, there hasn’t been an analysis that shows that this [exchange] actually makes sense, but I think it’s one of those analyses kind of showing people that the sky is blue but proving it quantitatively.”
Dr. Bollard said that the potential beneficial impact of such an exchange “is huge,” but it would “require upfront expenditure to actually realize these massive gains you will get down the road for these patients.”
Would be cost-effective
Although hospitals and transfusion centers check donated blood against an individual patient’s alloantibody profile, that information is usually kept in localized records and is not typically shared across health systems nationwide.
It’s different in the Netherlands, where the Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) was launched in 2007. Under this system, transfusion laboratories register the presence of irregular red blood cell alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing.
To see whether such a system, if implemented in the United States, would satisfy even the most parsimonious administrator or insurer, Dr. Goshua and colleagues created a computer simulation.
They estimated age- and gender-adjusted quality-adjusted life years (QALYs) for patients living with sickle cell disease, who typically require frequent transfusions and are thus especially at risk for developing alloantibodies and immune reactions from repeat exposures to the blood of others.
The model included age- and gender-adjusted costs based on 10 years of claims data, with the assumption that equal numbers of male and females would be in the sample.
The model estimated that by reducing DHTR incidence and DHTR-specific mortality in 20% to 44% of alloimmunized patients (a very conservative estimate, according to Dr. Goshua), the existence of a U.S. exchange would result in a gain of between 7,140 and 15,710 QALYs.
Assuming a willingness to pay up to $100,000 per QALY, a commonly used threshold in economic analyses in the United States, the exchange (vs. no exchange) would be preferred in 100% of 10,000 different iterations of a cost-effectiveness acceptability curve, Dr. Goshua said.
Even if the lifetime operational costs of such an exchange exceeded $600 million, it would still be cost-effective, and the net monetary benefit to the U.S. economy would be $0.7 billion, the authors found.
And although the model was limited to patients with sickle cell anemia, many other alloimmunized patients would be likely to benefit from such an exchange, including women with a prior pregnancy, and patients with autoimmunity, myelodysplastic syndrome, or beta-thalassemia, Dr. Goshua said.
The study was supported by the American Society of Hematology, the Yale School of Medicine, and Yale Center. Dr. Goshua and Dr. Bollard reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022
Beta-thalassemia: Benefits of gene therapy outweigh costs
Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.
The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.
The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.
The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.
As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.
“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.
Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.
The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.
As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.
When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.
There were also improvements on various quality of life scales, including in physical functioning and mental health.
Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.
On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.
As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.
No malignancies, insertional oncogenesis, or lentivirus replication have been observed.
The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.
Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.
The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.
The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.
The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.
As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.
“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.
Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.
The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.
As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.
When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.
There were also improvements on various quality of life scales, including in physical functioning and mental health.
Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.
On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.
As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.
No malignancies, insertional oncogenesis, or lentivirus replication have been observed.
The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.
Surveyed at 3 years, patients also reported ongoing benefits from treatment, including positive impacts on employment, school attendance, and physical activity, according to a second report.
The findings address a major question about betibeglogene autotemcel: Its durability. The therapy is priced at over $2 million per treatment, based on the premise that it will benefit patients in the long-term, in part by offsetting the cost of ongoing transfusions. Therefore, proof of long-standing benefit is important.
The Food and Drug Administration approved betibeglogene autotemcel in August 2022 for children and adults with transfusion dependent beta-thalassemia, a condition that causes patients to have absent or reduced levels of hemoglobin due to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks.
The treatment inserts functional copies of the mutated gene into the patients’ hematopoietic stem cells via a replication-defective lentivirus. The cells are then transfused back into the patient.
As of August 2021, 63 patients had undergone treatment and been followed for a median of 41.4 months. So far, durability looks solid.
“We now have up to 8 years efficacy and safety follow-up” with beti-cel. “Patients experience durable transfusion independence,” said Mark Walters, MD, a pediatric hematologist/oncologist at the University of California, San Francisco, who presented the long-term efficacy data at the meeting.
Overall, 89.5% of patients (34/38) in phase 3 testing achieved transfusion independence, meaning that they had hemoglobin levels of at least 9 g/dL without transfusions for a year or more.
The response rate was an improvement over phase 1/2 testing, in which 68% of subjects (15/22) became transfusion free. Improvements in the manufacturing process led to better outcomes in phase 3, Dr. Walters said.
As for quality of life (QoL), improvement “continues through 3 years following treatment,” said Franco Locatelli, MD, a pediatric hematologist/oncologist at Catholic University of the Sacred Heart, Rome, who led the QoL study.
When patients who achieved transfusion independence were surveyed 3 years after treatment, 93% of adults were employed or able to seek employment, up from 67% before treatment. School absences were down among children, almost half of subjects no longer needed symptom management, and 81% reported improvements in physical activity.
There were also improvements on various quality of life scales, including in physical functioning and mental health.
Patient age and underlying thalassemia genotype had no impact on the likelihood of transfusion independence. Those who achieved it also had reductions in markers of ineffective erythropoiesis and iron overload.
On multivariate analysis, the greatest predictor of transfusion independence was having at least 62% of cells transduced prior to reintroduction to the patient.
As for adverse events, seven subjects (11%) developed severe veno-occlusive liver disease that resolved with supportive care. Mucositis and febrile neutropenia are also a concern and related to the busulfan conditioning regimen.
No malignancies, insertional oncogenesis, or lentivirus replication have been observed.
The studies were funded by beti-cel maker Bluebird Bio, and many of the investigators are employees. Others reported ties to Bluebird and a range of other companies. Among his industry ties, Dr. Locatelli is a speaker for Bluebird. Dr. Walters also had industry relationships, but didn’t report any ties to Bluebird.
FROM ASH 2022
Cardiologist sues hospital, claims he was fired in retaliation
alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.
Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.
In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”
Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”
Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.
The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”
Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”
It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.
Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”
Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.
In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
Voiced concerns
In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.
“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.
He said he has “voiced concerns over several years and they have been ignored.”
He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.
“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.
In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.
This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.
A version of this article first appeared on Medscape.com.
alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.
Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.
In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”
Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”
Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.
The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”
Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”
It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.
Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”
Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.
In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
Voiced concerns
In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.
“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.
He said he has “voiced concerns over several years and they have been ignored.”
He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.
“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.
In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.
This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.
A version of this article first appeared on Medscape.com.
alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.
Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.
In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”
Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”
Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.
The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”
Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”
It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.
Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”
Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.
In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
Voiced concerns
In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.
“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.
He said he has “voiced concerns over several years and they have been ignored.”
He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.
“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.
In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.
This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.
A version of this article first appeared on Medscape.com.
‘Exciting’ responsiveness to talquetamab for r/r MM
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.
The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.
It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.
“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.
Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.
“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.
The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.
The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
MonumenTAL study
Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.
In the phase 1 dose-escalation study published in NEJM, the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
Three cohorts, two doses
The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.
There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.
The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.
The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
Phase 2 results
The overall response rate (ORR) among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).
The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.
The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).
The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
Safety profile
Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.
Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.
Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.
Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases with dose reductions.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
What’s next?
At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)
Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.
Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.
A version of this article first appeared on Medscape.com.
AT ASH 2022
Pricey gene therapy looks cost-effective for SCD
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS –
Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.
Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.
However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.
“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.
“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.
He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.
“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.
Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.
“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.
She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
Adding a D to CEA
Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.
A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”
The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.
As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
QALYs considered
Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.
The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.
In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.
In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.
Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.
However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.
Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.
Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.
“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.
The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2022
MCL: Ibrutinib could become the ‘new standard’
First-line patients fared well on ibrutinib, a Bruton’s tyrosine kinase inhibitor, according to the findings.
“Based on the results so far ... at least for the majority of patients, ibrutinib early will become the new standard,” said study lead author Martin Dreyling, MD, associate professor of medicine at Ludwig Maximilian University (LMU) Munich. Dr. Dreyling spoke in a news briefing and at a separate presentation at the annual meeting of the American Society of Hematology. “It might well be that specific subsets of patients may benefit from autologous transplant.”
MCL is a rare form of non-Hodgkin’s lymphoma that strikes cells in the mantle zone of lymph nodes. It is usually diagnosed in older men and often presents at an advanced stage. Multiple available treatments include rituximab/bendamustine, CAR-T cell therapy, stem cell transplants, and Bruton’s tyrosine kinase inhibitors. Ibrutinib is approved by the Food and Drug Administration only for refractory/relapsed cases, however.
Dr. Dreyling was a pioneer in confirming benefit from stem-cell transplants for MCL. “However,” he said, “no one likes autologous transplant because it also has side effects.”
For the new open-label study, Dr. Dreyling and colleagues in the European MCL Network in 2016 began recruiting patients with newly diagnosed, advanced stage II-IV MCL. The patients were younger than 65.
The subjects were randomly assigned to three trial arms: Standard treatment (high-dose cytarabine followed by autologous stem cell transplant and rituximab maintenance, n = 288), the standard treatment plus ibrutinib (n = 292), and ibrutinib without stem cell transplant (n = 290). The median age was 57, and 76% of patients were male.
The primary endpoint was failure-free survival at 31 months. Standard therapy was not superior to the ibrutinib without transplant group (72% vs. 86%, respectively, P = .9979). However, standard therapy with ibrutinib was superior to the standard therapy group (88% vs. 72%, respectively, P = .0008). The researchers haven’t finished their analysis of standard therapy with ibrutinib vs. ibrutinib without transplant.
Subjects in the standard therapy plus ibrutinib arm had more grade 3-5 adverse events than did the standard therapy and ibrutinib without transplant groups: Neutropenia, 44%, 17%, and 23%, respectively; leukopenia, 4%, 2%, and 2%; febrile neutropenia, 6%, 3%, and 3%; infections and infestations, 25%, 13%, and 19%; and cardiac disorders, 3%, 1%, 4%. P values were not provided.
In an interview, Ohio State University hematologist Narendranath Epperla, MD, MS, who was not involved in the study, said that this research reflects efforts to understand how novel agents such as ibrutinib and cellular therapies fit into MCL treatment. “We are trying to incorporate them in the frontline setting with either chemo backbone or with other targeted agents to improve outcomes and minimize toxicity. We are also trying to understand in whom auto-HCT can be precluded.”
The results of the new study appear promising, Dr. Epperla said, but he questioned the primary endpoint (failure-free survival instead of progress-free survival) and the short duration of the trial.
“I would like to see how the patients with high-risk features such as TP53 mutation, complex cytogenetics, and blastoid/pleomorphic variants did on the three arms,” Dr. Epperla said. “And I would like to see longer follow-up data before adapting this – [addition] of ibrutinib to the chemotherapy backbone without auto-HCT – into clinical practice.”
What’s next? Dr. Dreyling said that upcoming data will provide further insight into ibrutinib vs. stem-cell transplantation. And “within the next half year or so,” he said, “there will be a next generation of studies challenging chemotherapy overall in mantle cell lymphoma and substituting targeted treatment, hopefully achieving much better tolerability.”
Funding information was not provided. Dr. Dreyling disclosed ties with Lilly/Loxo, AstraZeneca, Novartis, Amgen, Roche, Janssen, Gilead/Kite, BMS/Celgene, Bayer, Abbvie, and Beigene. The other study authors reported various disclosures. Dr. Epperla disclosed a relationship with Pharmacyclics.
First-line patients fared well on ibrutinib, a Bruton’s tyrosine kinase inhibitor, according to the findings.
“Based on the results so far ... at least for the majority of patients, ibrutinib early will become the new standard,” said study lead author Martin Dreyling, MD, associate professor of medicine at Ludwig Maximilian University (LMU) Munich. Dr. Dreyling spoke in a news briefing and at a separate presentation at the annual meeting of the American Society of Hematology. “It might well be that specific subsets of patients may benefit from autologous transplant.”
MCL is a rare form of non-Hodgkin’s lymphoma that strikes cells in the mantle zone of lymph nodes. It is usually diagnosed in older men and often presents at an advanced stage. Multiple available treatments include rituximab/bendamustine, CAR-T cell therapy, stem cell transplants, and Bruton’s tyrosine kinase inhibitors. Ibrutinib is approved by the Food and Drug Administration only for refractory/relapsed cases, however.
Dr. Dreyling was a pioneer in confirming benefit from stem-cell transplants for MCL. “However,” he said, “no one likes autologous transplant because it also has side effects.”
For the new open-label study, Dr. Dreyling and colleagues in the European MCL Network in 2016 began recruiting patients with newly diagnosed, advanced stage II-IV MCL. The patients were younger than 65.
The subjects were randomly assigned to three trial arms: Standard treatment (high-dose cytarabine followed by autologous stem cell transplant and rituximab maintenance, n = 288), the standard treatment plus ibrutinib (n = 292), and ibrutinib without stem cell transplant (n = 290). The median age was 57, and 76% of patients were male.
The primary endpoint was failure-free survival at 31 months. Standard therapy was not superior to the ibrutinib without transplant group (72% vs. 86%, respectively, P = .9979). However, standard therapy with ibrutinib was superior to the standard therapy group (88% vs. 72%, respectively, P = .0008). The researchers haven’t finished their analysis of standard therapy with ibrutinib vs. ibrutinib without transplant.
Subjects in the standard therapy plus ibrutinib arm had more grade 3-5 adverse events than did the standard therapy and ibrutinib without transplant groups: Neutropenia, 44%, 17%, and 23%, respectively; leukopenia, 4%, 2%, and 2%; febrile neutropenia, 6%, 3%, and 3%; infections and infestations, 25%, 13%, and 19%; and cardiac disorders, 3%, 1%, 4%. P values were not provided.
In an interview, Ohio State University hematologist Narendranath Epperla, MD, MS, who was not involved in the study, said that this research reflects efforts to understand how novel agents such as ibrutinib and cellular therapies fit into MCL treatment. “We are trying to incorporate them in the frontline setting with either chemo backbone or with other targeted agents to improve outcomes and minimize toxicity. We are also trying to understand in whom auto-HCT can be precluded.”
The results of the new study appear promising, Dr. Epperla said, but he questioned the primary endpoint (failure-free survival instead of progress-free survival) and the short duration of the trial.
“I would like to see how the patients with high-risk features such as TP53 mutation, complex cytogenetics, and blastoid/pleomorphic variants did on the three arms,” Dr. Epperla said. “And I would like to see longer follow-up data before adapting this – [addition] of ibrutinib to the chemotherapy backbone without auto-HCT – into clinical practice.”
What’s next? Dr. Dreyling said that upcoming data will provide further insight into ibrutinib vs. stem-cell transplantation. And “within the next half year or so,” he said, “there will be a next generation of studies challenging chemotherapy overall in mantle cell lymphoma and substituting targeted treatment, hopefully achieving much better tolerability.”
Funding information was not provided. Dr. Dreyling disclosed ties with Lilly/Loxo, AstraZeneca, Novartis, Amgen, Roche, Janssen, Gilead/Kite, BMS/Celgene, Bayer, Abbvie, and Beigene. The other study authors reported various disclosures. Dr. Epperla disclosed a relationship with Pharmacyclics.
First-line patients fared well on ibrutinib, a Bruton’s tyrosine kinase inhibitor, according to the findings.
“Based on the results so far ... at least for the majority of patients, ibrutinib early will become the new standard,” said study lead author Martin Dreyling, MD, associate professor of medicine at Ludwig Maximilian University (LMU) Munich. Dr. Dreyling spoke in a news briefing and at a separate presentation at the annual meeting of the American Society of Hematology. “It might well be that specific subsets of patients may benefit from autologous transplant.”
MCL is a rare form of non-Hodgkin’s lymphoma that strikes cells in the mantle zone of lymph nodes. It is usually diagnosed in older men and often presents at an advanced stage. Multiple available treatments include rituximab/bendamustine, CAR-T cell therapy, stem cell transplants, and Bruton’s tyrosine kinase inhibitors. Ibrutinib is approved by the Food and Drug Administration only for refractory/relapsed cases, however.
Dr. Dreyling was a pioneer in confirming benefit from stem-cell transplants for MCL. “However,” he said, “no one likes autologous transplant because it also has side effects.”
For the new open-label study, Dr. Dreyling and colleagues in the European MCL Network in 2016 began recruiting patients with newly diagnosed, advanced stage II-IV MCL. The patients were younger than 65.
The subjects were randomly assigned to three trial arms: Standard treatment (high-dose cytarabine followed by autologous stem cell transplant and rituximab maintenance, n = 288), the standard treatment plus ibrutinib (n = 292), and ibrutinib without stem cell transplant (n = 290). The median age was 57, and 76% of patients were male.
The primary endpoint was failure-free survival at 31 months. Standard therapy was not superior to the ibrutinib without transplant group (72% vs. 86%, respectively, P = .9979). However, standard therapy with ibrutinib was superior to the standard therapy group (88% vs. 72%, respectively, P = .0008). The researchers haven’t finished their analysis of standard therapy with ibrutinib vs. ibrutinib without transplant.
Subjects in the standard therapy plus ibrutinib arm had more grade 3-5 adverse events than did the standard therapy and ibrutinib without transplant groups: Neutropenia, 44%, 17%, and 23%, respectively; leukopenia, 4%, 2%, and 2%; febrile neutropenia, 6%, 3%, and 3%; infections and infestations, 25%, 13%, and 19%; and cardiac disorders, 3%, 1%, 4%. P values were not provided.
In an interview, Ohio State University hematologist Narendranath Epperla, MD, MS, who was not involved in the study, said that this research reflects efforts to understand how novel agents such as ibrutinib and cellular therapies fit into MCL treatment. “We are trying to incorporate them in the frontline setting with either chemo backbone or with other targeted agents to improve outcomes and minimize toxicity. We are also trying to understand in whom auto-HCT can be precluded.”
The results of the new study appear promising, Dr. Epperla said, but he questioned the primary endpoint (failure-free survival instead of progress-free survival) and the short duration of the trial.
“I would like to see how the patients with high-risk features such as TP53 mutation, complex cytogenetics, and blastoid/pleomorphic variants did on the three arms,” Dr. Epperla said. “And I would like to see longer follow-up data before adapting this – [addition] of ibrutinib to the chemotherapy backbone without auto-HCT – into clinical practice.”
What’s next? Dr. Dreyling said that upcoming data will provide further insight into ibrutinib vs. stem-cell transplantation. And “within the next half year or so,” he said, “there will be a next generation of studies challenging chemotherapy overall in mantle cell lymphoma and substituting targeted treatment, hopefully achieving much better tolerability.”
Funding information was not provided. Dr. Dreyling disclosed ties with Lilly/Loxo, AstraZeneca, Novartis, Amgen, Roche, Janssen, Gilead/Kite, BMS/Celgene, Bayer, Abbvie, and Beigene. The other study authors reported various disclosures. Dr. Epperla disclosed a relationship with Pharmacyclics.
AT ASH 2022
Why doctors are losing trust in patients; what should be done?
This transcript has been edited for clarity.
Hi. I’m Art Caplan. I’m at the division of medical ethics at New York University.
I want to talk about a paper that my colleagues in my division just published in Health Affairs.
As they pointed out, there’s a large amount of literature about what makes patients trust their doctor. There are many studies that show that, although patients sometimes have become more critical of the medical profession, in general they still try to trust their individual physician. Nurses remain in fairly high esteem among those who are getting hospital care.
What isn’t studied, as this paper properly points out, is, what can the doctor and the nurse do to trust the patient? How can that be assessed? Isn’t that just as important as saying that patients have to trust their doctors to do and comply with what they’re told?
What if doctors are afraid of violence? What if doctors are fearful that they can’t trust patients to listen, pay attention, or do what they’re being told? What if they think that patients are coming in with all kinds of disinformation, false information, or things they pick up on the Internet, so that even though you try your best to get across accurate and complete information about what to do about infectious diseases, taking care of a kid with strep throat, or whatever it might be, you’re thinking, Can I trust this patient to do what it is that I want them to do?
One particular problem that’s causing distrust is that more and more patients are showing stress and dependence on drugs and alcohol. That doesn’t make them less trustworthy per se, but it means they can’t regulate their own behavior as well.
That obviously has to be something that the physician or the nurse is thinking about. Is this person going to be able to contain anger? Is this person going to be able to handle bad news? Is this person going to deal with me when I tell them that some of the things they believe to be true about what’s good for their health care are false?
I think we have to really start to push administrators and people in positions of power to teach doctors and nurses how to defuse situations and how to make people more comfortable when they come in and the doctor suspects that they might be under the influence, impaired, or angry because of things they’ve seen on social media, whatever those might be – including concerns about racism, bigotry, and bias, which some patients are bringing into the clinic and the hospital setting.
We need more training. We’ve got to address this as a serious issue. What can we do to defuse situations where the doctor or the nurse rightly thinks that they can’t control or they can’t trust what the patient is thinking or how the patient might behave?
It’s also the case that I think we need more backup and quick access to security so that people feel safe and comfortable in providing care. We have to make sure that if you need someone to restrain a patient or to get somebody out of a situation, that they can get there quickly and respond rapidly, and that they know what to do to deescalate a situation.
It’s sad to say, but security in today’s health care world has to be something that we really test and check – not because we’re worried, as many places are, about a shooter entering the premises, which is its own bit of concern – but I’m just talking about when the doctor or the nurse says that this patient might be acting up, could get violent, or is someone I can’t trust.
My coauthors are basically saying that it’s not a one-way street. Yes, we have to figure out ways to make sure that our patients can trust what we say. Trust is absolutely the lubricant that makes health care flow. If patients don’t trust their doctors, they’re not going to do what they say. They’re not going to get their prescriptions filled. They’re not going to be compliant. They’re not going to try to lose weight or control their diabetes.
It also goes the other way. The doctor or the nurse has to trust the patient. They have to believe that they’re safe. They have to believe that the patient is capable of controlling themselves. They have to believe that the patient is capable of listening and hearing what they’re saying, and that they’re competent to follow up on instructions, including to come back if that’s what’s required.
Everybody has to feel secure in the environment in which they’re working. Security, sadly, has to be a priority if we’re going to have a health care workforce that really feels safe and comfortable dealing with a patient population that is increasingly aggressive and perhaps not as trustworthy.
That’s not news I like to read when my colleagues write it up, but it’s important and we have to take it seriously.
Dr. Caplan disclosed that he has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position), and is a contributing author and adviser for Medscape. A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hi. I’m Art Caplan. I’m at the division of medical ethics at New York University.
I want to talk about a paper that my colleagues in my division just published in Health Affairs.
As they pointed out, there’s a large amount of literature about what makes patients trust their doctor. There are many studies that show that, although patients sometimes have become more critical of the medical profession, in general they still try to trust their individual physician. Nurses remain in fairly high esteem among those who are getting hospital care.
What isn’t studied, as this paper properly points out, is, what can the doctor and the nurse do to trust the patient? How can that be assessed? Isn’t that just as important as saying that patients have to trust their doctors to do and comply with what they’re told?
What if doctors are afraid of violence? What if doctors are fearful that they can’t trust patients to listen, pay attention, or do what they’re being told? What if they think that patients are coming in with all kinds of disinformation, false information, or things they pick up on the Internet, so that even though you try your best to get across accurate and complete information about what to do about infectious diseases, taking care of a kid with strep throat, or whatever it might be, you’re thinking, Can I trust this patient to do what it is that I want them to do?
One particular problem that’s causing distrust is that more and more patients are showing stress and dependence on drugs and alcohol. That doesn’t make them less trustworthy per se, but it means they can’t regulate their own behavior as well.
That obviously has to be something that the physician or the nurse is thinking about. Is this person going to be able to contain anger? Is this person going to be able to handle bad news? Is this person going to deal with me when I tell them that some of the things they believe to be true about what’s good for their health care are false?
I think we have to really start to push administrators and people in positions of power to teach doctors and nurses how to defuse situations and how to make people more comfortable when they come in and the doctor suspects that they might be under the influence, impaired, or angry because of things they’ve seen on social media, whatever those might be – including concerns about racism, bigotry, and bias, which some patients are bringing into the clinic and the hospital setting.
We need more training. We’ve got to address this as a serious issue. What can we do to defuse situations where the doctor or the nurse rightly thinks that they can’t control or they can’t trust what the patient is thinking or how the patient might behave?
It’s also the case that I think we need more backup and quick access to security so that people feel safe and comfortable in providing care. We have to make sure that if you need someone to restrain a patient or to get somebody out of a situation, that they can get there quickly and respond rapidly, and that they know what to do to deescalate a situation.
It’s sad to say, but security in today’s health care world has to be something that we really test and check – not because we’re worried, as many places are, about a shooter entering the premises, which is its own bit of concern – but I’m just talking about when the doctor or the nurse says that this patient might be acting up, could get violent, or is someone I can’t trust.
My coauthors are basically saying that it’s not a one-way street. Yes, we have to figure out ways to make sure that our patients can trust what we say. Trust is absolutely the lubricant that makes health care flow. If patients don’t trust their doctors, they’re not going to do what they say. They’re not going to get their prescriptions filled. They’re not going to be compliant. They’re not going to try to lose weight or control their diabetes.
It also goes the other way. The doctor or the nurse has to trust the patient. They have to believe that they’re safe. They have to believe that the patient is capable of controlling themselves. They have to believe that the patient is capable of listening and hearing what they’re saying, and that they’re competent to follow up on instructions, including to come back if that’s what’s required.
Everybody has to feel secure in the environment in which they’re working. Security, sadly, has to be a priority if we’re going to have a health care workforce that really feels safe and comfortable dealing with a patient population that is increasingly aggressive and perhaps not as trustworthy.
That’s not news I like to read when my colleagues write it up, but it’s important and we have to take it seriously.
Dr. Caplan disclosed that he has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position), and is a contributing author and adviser for Medscape. A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hi. I’m Art Caplan. I’m at the division of medical ethics at New York University.
I want to talk about a paper that my colleagues in my division just published in Health Affairs.
As they pointed out, there’s a large amount of literature about what makes patients trust their doctor. There are many studies that show that, although patients sometimes have become more critical of the medical profession, in general they still try to trust their individual physician. Nurses remain in fairly high esteem among those who are getting hospital care.
What isn’t studied, as this paper properly points out, is, what can the doctor and the nurse do to trust the patient? How can that be assessed? Isn’t that just as important as saying that patients have to trust their doctors to do and comply with what they’re told?
What if doctors are afraid of violence? What if doctors are fearful that they can’t trust patients to listen, pay attention, or do what they’re being told? What if they think that patients are coming in with all kinds of disinformation, false information, or things they pick up on the Internet, so that even though you try your best to get across accurate and complete information about what to do about infectious diseases, taking care of a kid with strep throat, or whatever it might be, you’re thinking, Can I trust this patient to do what it is that I want them to do?
One particular problem that’s causing distrust is that more and more patients are showing stress and dependence on drugs and alcohol. That doesn’t make them less trustworthy per se, but it means they can’t regulate their own behavior as well.
That obviously has to be something that the physician or the nurse is thinking about. Is this person going to be able to contain anger? Is this person going to be able to handle bad news? Is this person going to deal with me when I tell them that some of the things they believe to be true about what’s good for their health care are false?
I think we have to really start to push administrators and people in positions of power to teach doctors and nurses how to defuse situations and how to make people more comfortable when they come in and the doctor suspects that they might be under the influence, impaired, or angry because of things they’ve seen on social media, whatever those might be – including concerns about racism, bigotry, and bias, which some patients are bringing into the clinic and the hospital setting.
We need more training. We’ve got to address this as a serious issue. What can we do to defuse situations where the doctor or the nurse rightly thinks that they can’t control or they can’t trust what the patient is thinking or how the patient might behave?
It’s also the case that I think we need more backup and quick access to security so that people feel safe and comfortable in providing care. We have to make sure that if you need someone to restrain a patient or to get somebody out of a situation, that they can get there quickly and respond rapidly, and that they know what to do to deescalate a situation.
It’s sad to say, but security in today’s health care world has to be something that we really test and check – not because we’re worried, as many places are, about a shooter entering the premises, which is its own bit of concern – but I’m just talking about when the doctor or the nurse says that this patient might be acting up, could get violent, or is someone I can’t trust.
My coauthors are basically saying that it’s not a one-way street. Yes, we have to figure out ways to make sure that our patients can trust what we say. Trust is absolutely the lubricant that makes health care flow. If patients don’t trust their doctors, they’re not going to do what they say. They’re not going to get their prescriptions filled. They’re not going to be compliant. They’re not going to try to lose weight or control their diabetes.
It also goes the other way. The doctor or the nurse has to trust the patient. They have to believe that they’re safe. They have to believe that the patient is capable of controlling themselves. They have to believe that the patient is capable of listening and hearing what they’re saying, and that they’re competent to follow up on instructions, including to come back if that’s what’s required.
Everybody has to feel secure in the environment in which they’re working. Security, sadly, has to be a priority if we’re going to have a health care workforce that really feels safe and comfortable dealing with a patient population that is increasingly aggressive and perhaps not as trustworthy.
That’s not news I like to read when my colleagues write it up, but it’s important and we have to take it seriously.
Dr. Caplan disclosed that he has served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position), and is a contributing author and adviser for Medscape. A version of this article first appeared on Medscape.com.
Statins tied to lower ICH risk regardless of bleed location
A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.
The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.
The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.
“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.
“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”
The study was published online in Neurology.
The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.
Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.
However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.
The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.
The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.
These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.
The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.
Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.
For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).
Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.
For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).
“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”
Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.
“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.
“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.
He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
Interaction with antihypertensives, anticoagulants?
Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.
Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.
Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.
Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”
However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.
“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.
Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.
“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.
The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.
A version of this article first appeared on Medscape.com.
A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.
The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.
The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.
“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.
“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”
The study was published online in Neurology.
The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.
Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.
However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.
The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.
The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.
These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.
The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.
Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.
For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).
Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.
For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).
“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”
Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.
“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.
“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.
He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
Interaction with antihypertensives, anticoagulants?
Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.
Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.
Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.
Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”
However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.
“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.
Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.
“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.
The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.
A version of this article first appeared on Medscape.com.
A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.
The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.
The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.
“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.
“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”
The study was published online in Neurology.
The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.
Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.
However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.
The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.
The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.
These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.
The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.
Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.
For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).
Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.
For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).
“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”
Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.
“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.
“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.
He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
Interaction with antihypertensives, anticoagulants?
Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.
Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.
Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.
Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”
However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.
“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.
Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.
“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.
The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.
A version of this article first appeared on Medscape.com.