A fourth dose of the Pfizer-BioNTech vaccine is effective in reducing the short-term risk for COVID-19 infection, hospitalization, and death in people who got a third dose at least 4 months before, a large study shows.

However, Paul Offit, MD, author of an editorial accompanying the study, told this news organization, “I would argue, without fear of contradiction, that this is going to have no impact on this pandemic.”

“We are still in the midst of a zero-tolerance policy for this virus. We don’t accept mild illness and if we’re not going to accept mild illness, we think we have to boost it away, which would mean probably about two doses every year. That’s not a reasonable public health strategy,” said Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
 

Booster confusion

Results of the research out of Israel, published in the New England Journal of Medicine, make a case for a fourth booster for people 60 and over.

Researchers, led by Ori Magen, MD, Clalit Research Institute, innovation division, Clalit Health Services, Tel Aviv, analyzed data comparing 182,122 matched pairs recorded by the largest health care organization in Israel from Jan. 3 to Feb. 18, 2022. With more than 4.7 million members, Clalit Health Services covers more than half of the population of Israel.

The researchers compared outcomes in people 60 or older (average age, 72 years) who got a fourth dose with outcomes in those who had only a third dose. They individually matched people from the two groups, considering factors such as age, health status, and ethnicity.

Relative vaccine effectiveness in days 7-30 after the fourth dose was estimated to be 45% (95% confidence interval, 44%-47%) against confirmed SARS-CoV-2 infection, 55% (95% CI, 53%-58%) against symptomatic COVID-19, 68% (95% CI, 59%-74%) against hospitalization, 62% (95% CI, 50%-74%) against severe COVID, and 74% (95% CI, 50%-90%) against COVID-related death.

Several countries, including the United States, have begun offering a fourth vaccine dose for higher-risk populations in light of evidence of waning immunity after the third dose and waves of infection, driven by Omicron and its variants, in some parts of the world. But the recommended age groups differ considerably.

In the United States, for instance, the Food and Drug Administration in late March approved a fourth dose of the Pfizer or Moderna vaccine for anyone over 50 and people over 18 who have gotten a solid organ transplant or have a similar level of immune risk.

Dr. Offit pointed out that Israel offers the fourth vaccine for people 60 and over and the European Medical Association offers it for those over 80. No surprise that confusion over the fourth dose is rampant.
 

Booster advice

Dr. Offit offered this perspective: People who are immunocompromised could reasonably get a fourth dose, depending on the manner in which they are compromised.

“Someone who has a solid organ transplant is not the same as someone who is getting a monoclonal antibody for their rheumatoid arthritis,” Dr. Offit said, adding that people could also make a reasonable argument for the fourth dose if they are over 65 and have multiple comorbidities.

“I’m over 65,” Dr. Offit said. “I’m generally healthy. I’m not going to get a fourth dose.”

People with multiple comorbidities over age 12 could reasonably get a third dose, he said. “For everybody else – healthy people less than 65 – I would argue this is a two-dose vaccine.”

CHOP, he noted as an example, mandates the vaccine but doesn’t mandate three doses and he says that’s not unusual for hospital systems.

“How many lives are you really saving with that fourth dose? If you really want to have an effect on this pandemic, vaccinate the unvaccinated,” Dr. Offit said.
 

Focus on the memory cells

Dr. Offit wrote in the editorial: “Arguably, the most disappointing error surrounding the use of COVID-19 vaccines was the labeling of mild illnesses or asymptomatic infections after vaccination as ‘breakthroughs.’ As is true for all mucosal vaccines, the goal is to protect against serious illness – to keep people out of the hospital, intensive care unit, and morgue. The term ‘breakthrough,’ which implies failure, created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus.”

Dr. Offit said that the focus should be on the memory cells, not the neutralizing antibodies.

Regarding mRNA vaccines, Dr. Offit said “the surprise of this vaccine – it surprised me and other vaccine researchers – is that with these two doses of mRNA separated by 3-4 weeks, you actually appear to have long-lived memory response.

“That’s not the history of vaccines. If you look at the inactivated polio vaccine or the inactivated hepatitis A vaccine, you really do need a 4- to 6-month interval between doses to get high frequencies of memory cells. That doesn’t appear to be the case here. It looks like two doses given close together do just that. Memory cells last for years if not, sometimes, decades.”

Neutralizing antibodies, on the other hand, protect against mild illness and their effectiveness wanes after months.

“At some point we are going to have to get used to mild illness,” Dr. Offit said.

The Centers for Disease Control and Prevention must now determine who will benefit most from booster dosing and educate the public about the limits of mucosal vaccines, Dr. Offit wrote in the editorial.

“Otherwise, a zero-tolerance strategy for mild or asymptomatic infection, which can be implemented only with frequent booster doses, will continue to mislead the public about what COVID-19 vaccines can and cannot do.”

The work was funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

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

A fourth dose of the Pfizer-BioNTech vaccine is effective in reducing the short-term risk for COVID-19 infection, hospitalization, and death in people who got a third dose at least 4 months before, a large study shows.

However, Paul Offit, MD, author of an editorial accompanying the study, told this news organization, “I would argue, without fear of contradiction, that this is going to have no impact on this pandemic.”

“We are still in the midst of a zero-tolerance policy for this virus. We don’t accept mild illness and if we’re not going to accept mild illness, we think we have to boost it away, which would mean probably about two doses every year. That’s not a reasonable public health strategy,” said Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
 

Booster confusion

Results of the research out of Israel, published in the New England Journal of Medicine, make a case for a fourth booster for people 60 and over.

Researchers, led by Ori Magen, MD, Clalit Research Institute, innovation division, Clalit Health Services, Tel Aviv, analyzed data comparing 182,122 matched pairs recorded by the largest health care organization in Israel from Jan. 3 to Feb. 18, 2022. With more than 4.7 million members, Clalit Health Services covers more than half of the population of Israel.

The researchers compared outcomes in people 60 or older (average age, 72 years) who got a fourth dose with outcomes in those who had only a third dose. They individually matched people from the two groups, considering factors such as age, health status, and ethnicity.

Relative vaccine effectiveness in days 7-30 after the fourth dose was estimated to be 45% (95% confidence interval, 44%-47%) against confirmed SARS-CoV-2 infection, 55% (95% CI, 53%-58%) against symptomatic COVID-19, 68% (95% CI, 59%-74%) against hospitalization, 62% (95% CI, 50%-74%) against severe COVID, and 74% (95% CI, 50%-90%) against COVID-related death.

Several countries, including the United States, have begun offering a fourth vaccine dose for higher-risk populations in light of evidence of waning immunity after the third dose and waves of infection, driven by Omicron and its variants, in some parts of the world. But the recommended age groups differ considerably.

In the United States, for instance, the Food and Drug Administration in late March approved a fourth dose of the Pfizer or Moderna vaccine for anyone over 50 and people over 18 who have gotten a solid organ transplant or have a similar level of immune risk.

Dr. Offit pointed out that Israel offers the fourth vaccine for people 60 and over and the European Medical Association offers it for those over 80. No surprise that confusion over the fourth dose is rampant.
 

Booster advice

Dr. Offit offered this perspective: People who are immunocompromised could reasonably get a fourth dose, depending on the manner in which they are compromised.

“Someone who has a solid organ transplant is not the same as someone who is getting a monoclonal antibody for their rheumatoid arthritis,” Dr. Offit said, adding that people could also make a reasonable argument for the fourth dose if they are over 65 and have multiple comorbidities.

“I’m over 65,” Dr. Offit said. “I’m generally healthy. I’m not going to get a fourth dose.”

People with multiple comorbidities over age 12 could reasonably get a third dose, he said. “For everybody else – healthy people less than 65 – I would argue this is a two-dose vaccine.”

CHOP, he noted as an example, mandates the vaccine but doesn’t mandate three doses and he says that’s not unusual for hospital systems.

“How many lives are you really saving with that fourth dose? If you really want to have an effect on this pandemic, vaccinate the unvaccinated,” Dr. Offit said.
 

Focus on the memory cells

Dr. Offit wrote in the editorial: “Arguably, the most disappointing error surrounding the use of COVID-19 vaccines was the labeling of mild illnesses or asymptomatic infections after vaccination as ‘breakthroughs.’ As is true for all mucosal vaccines, the goal is to protect against serious illness – to keep people out of the hospital, intensive care unit, and morgue. The term ‘breakthrough,’ which implies failure, created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus.”

Dr. Offit said that the focus should be on the memory cells, not the neutralizing antibodies.

Regarding mRNA vaccines, Dr. Offit said “the surprise of this vaccine – it surprised me and other vaccine researchers – is that with these two doses of mRNA separated by 3-4 weeks, you actually appear to have long-lived memory response.

“That’s not the history of vaccines. If you look at the inactivated polio vaccine or the inactivated hepatitis A vaccine, you really do need a 4- to 6-month interval between doses to get high frequencies of memory cells. That doesn’t appear to be the case here. It looks like two doses given close together do just that. Memory cells last for years if not, sometimes, decades.”

Neutralizing antibodies, on the other hand, protect against mild illness and their effectiveness wanes after months.

“At some point we are going to have to get used to mild illness,” Dr. Offit said.

The Centers for Disease Control and Prevention must now determine who will benefit most from booster dosing and educate the public about the limits of mucosal vaccines, Dr. Offit wrote in the editorial.

“Otherwise, a zero-tolerance strategy for mild or asymptomatic infection, which can be implemented only with frequent booster doses, will continue to mislead the public about what COVID-19 vaccines can and cannot do.”

The work was funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

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

A fourth dose of the Pfizer-BioNTech vaccine is effective in reducing the short-term risk for COVID-19 infection, hospitalization, and death in people who got a third dose at least 4 months before, a large study shows.

However, Paul Offit, MD, author of an editorial accompanying the study, told this news organization, “I would argue, without fear of contradiction, that this is going to have no impact on this pandemic.”

“We are still in the midst of a zero-tolerance policy for this virus. We don’t accept mild illness and if we’re not going to accept mild illness, we think we have to boost it away, which would mean probably about two doses every year. That’s not a reasonable public health strategy,” said Dr. Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
 

Booster confusion

Results of the research out of Israel, published in the New England Journal of Medicine, make a case for a fourth booster for people 60 and over.

Researchers, led by Ori Magen, MD, Clalit Research Institute, innovation division, Clalit Health Services, Tel Aviv, analyzed data comparing 182,122 matched pairs recorded by the largest health care organization in Israel from Jan. 3 to Feb. 18, 2022. With more than 4.7 million members, Clalit Health Services covers more than half of the population of Israel.

The researchers compared outcomes in people 60 or older (average age, 72 years) who got a fourth dose with outcomes in those who had only a third dose. They individually matched people from the two groups, considering factors such as age, health status, and ethnicity.

Relative vaccine effectiveness in days 7-30 after the fourth dose was estimated to be 45% (95% confidence interval, 44%-47%) against confirmed SARS-CoV-2 infection, 55% (95% CI, 53%-58%) against symptomatic COVID-19, 68% (95% CI, 59%-74%) against hospitalization, 62% (95% CI, 50%-74%) against severe COVID, and 74% (95% CI, 50%-90%) against COVID-related death.

Several countries, including the United States, have begun offering a fourth vaccine dose for higher-risk populations in light of evidence of waning immunity after the third dose and waves of infection, driven by Omicron and its variants, in some parts of the world. But the recommended age groups differ considerably.

In the United States, for instance, the Food and Drug Administration in late March approved a fourth dose of the Pfizer or Moderna vaccine for anyone over 50 and people over 18 who have gotten a solid organ transplant or have a similar level of immune risk.

Dr. Offit pointed out that Israel offers the fourth vaccine for people 60 and over and the European Medical Association offers it for those over 80. No surprise that confusion over the fourth dose is rampant.
 

Booster advice

Dr. Offit offered this perspective: People who are immunocompromised could reasonably get a fourth dose, depending on the manner in which they are compromised.

“Someone who has a solid organ transplant is not the same as someone who is getting a monoclonal antibody for their rheumatoid arthritis,” Dr. Offit said, adding that people could also make a reasonable argument for the fourth dose if they are over 65 and have multiple comorbidities.

“I’m over 65,” Dr. Offit said. “I’m generally healthy. I’m not going to get a fourth dose.”

People with multiple comorbidities over age 12 could reasonably get a third dose, he said. “For everybody else – healthy people less than 65 – I would argue this is a two-dose vaccine.”

CHOP, he noted as an example, mandates the vaccine but doesn’t mandate three doses and he says that’s not unusual for hospital systems.

“How many lives are you really saving with that fourth dose? If you really want to have an effect on this pandemic, vaccinate the unvaccinated,” Dr. Offit said.
 

Focus on the memory cells

Dr. Offit wrote in the editorial: “Arguably, the most disappointing error surrounding the use of COVID-19 vaccines was the labeling of mild illnesses or asymptomatic infections after vaccination as ‘breakthroughs.’ As is true for all mucosal vaccines, the goal is to protect against serious illness – to keep people out of the hospital, intensive care unit, and morgue. The term ‘breakthrough,’ which implies failure, created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus.”

Dr. Offit said that the focus should be on the memory cells, not the neutralizing antibodies.

Regarding mRNA vaccines, Dr. Offit said “the surprise of this vaccine – it surprised me and other vaccine researchers – is that with these two doses of mRNA separated by 3-4 weeks, you actually appear to have long-lived memory response.

“That’s not the history of vaccines. If you look at the inactivated polio vaccine or the inactivated hepatitis A vaccine, you really do need a 4- to 6-month interval between doses to get high frequencies of memory cells. That doesn’t appear to be the case here. It looks like two doses given close together do just that. Memory cells last for years if not, sometimes, decades.”

Neutralizing antibodies, on the other hand, protect against mild illness and their effectiveness wanes after months.

“At some point we are going to have to get used to mild illness,” Dr. Offit said.

The Centers for Disease Control and Prevention must now determine who will benefit most from booster dosing and educate the public about the limits of mucosal vaccines, Dr. Offit wrote in the editorial.

“Otherwise, a zero-tolerance strategy for mild or asymptomatic infection, which can be implemented only with frequent booster doses, will continue to mislead the public about what COVID-19 vaccines can and cannot do.”

The work was funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

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

A jury last month found in favor of a West Virginia man who was permanently paralyzed following spinal cord surgery, according to a report by WOWK13 News, a local CBS affiliate in Huntington and Charleston, W. Va., among other news outlets.

On or about June 4, 2017, Michael Rodgers sustained injuries while riding his motorcycle. Admitted to Charleston Area Medical Center’s (CAMC’s) Level I trauma center, he initially showed no neurologic impairment and was able to feel and move all his extremities. A subsequent CT scan revealed, though, that he had incurred a T5 Chance fracture, as his later complaint states.

On June 6, a neurosurgeon affiliated with CAMC, John Orphanos, MD, instructed Mr. Rodgers to wear a back brace for 6 to 8 weeks. Later that day, though, Dr. Orphanos changed his course of treatment and recommended that Mr. Rodgers undergo surgery to treat his injuries. Despite his new recommendation, the neurosurgeon/spine specialist didn’t order a presurgical MRI of his patient’s thoracic spine. Typically, such a scan would have been used to determine any existing or potential spinal cord problems and any soft-tissue problems in the area of the fracture.

Not having such information, Dr. Orphanos was unaware that his patient had “an abundance of epidural fat, cord compression, cord edema, spinal abnormality, and spinal cord injury,” the complaint states. The neurosurgeon’s operative plan, therefore, included neither decompression of the spinal column nor use of neurophysiologic intraoperative monitoring, which is used to gauge, in real time during procedures, both how fast and how strongly a patient’s nerves are carrying signals.

Late on June 6, Dr. Orphanos performed a surgery to fuse his patient’s vertebrae from the T2 to the T6 region. Following the procedure, however, Mr. Rodgers experienced a complete loss of motor function and sensation in his lower extremities. A postoperative MRI proved inconclusive because of certain distorting effects of hardware implanted during the original surgery. Had a CT myelogram been ordered, it would have yielded a more accurate picture, the plaintiff alleged in his complaint.

Mr. Rodgers underwent a second surgery, during which Dr. Orphanos performed a T5 laminectomy. The patient’s loss of motor function and sensation persisted, however. He has been experiencing T5-level paraplegia ever since, with complete loss of control of his legs, bowel, and bladder.

In his complaint, Mr. Rodgers alleged that Dr. Orphanos had repeatedly deviated from the standard of care. Among other things, the plaintiff claimed, Dr. Orphanos had failed in both of his surgeries to order the proper preop and postop testing, thereby jeopardizing the outcomes of each procedure. This gross negligence and recklessness, the plaintiff argued, led directly to his permanent and disabling injuries.

Late last month, a West Virginia jury agreed that Dr. Orphanos was at fault and awarded Mr. Rodgers $17 million in damages.

Commented one of the pair of attorneys representing Mr. Rodgers: “We are very grateful to the jury, who saw through the attempts to rationalize the defendant’s conduct and delivered a jury verdict that will take care of Mr. Rodgers and provide the services he will need.”
 

Provider-to-provider disputes not time sensitive, state high court says

Early last month, Indiana’s high court ruled that the state’s med-mal statute of limitations doesn’t apply to disputes between providers, as a story in Radiology Business and other news sites reports.

The legal wrangling dates to April 2011. At that time, Joseph Shaughnessy underwent two CT scans at a Franciscan Alliance hospital, part of a healthcare system run by Franciscan Health. Outside radiologists from Lake Imaging read the scans, but they allegedly failed to note bleeding on the right side of the patient’s brain. Mr. Shaughnessy subsequently died, and his family filed suit against Franciscan, on the assumption that the radiologists were employees.

In 2015, the plaintiffs and Franciscan reached a $187,000 settlement, but Franciscan claimed it wasn’t liable for the payment, citing a clause in its prior agreement with Lake Imaging that protected it. But Lake Imaging sought to dismiss the Franciscan claim, arguing that the hospital system had failed to bring its suit within the state’s 2-year med-mal statute of limitations.

In its review of the case, the Indiana Supreme Court dismissed this argument: “(T)here is nothing in the [Medical Malpractice Act] to suggest that it extends beyond the physician-patient relationship to encompass commercial contracts between healthcare providers.”

In other words, while Indiana law places a 2-year limit on patients suing a hospital, doctor, or other healthcare professional, it places no such limit on contractually bound providers who take steps to sue each other.

As part of its unanimous decision, the high court also sent a claim by Lake Imaging against its insurance provider back to the trial court. The claim asks the insurance carrier — and not Lake Imaging — to assume responsibility for the settlement between Mr. Shaughnessy and Franciscan Alliance.

There was no word at press time as to when further legal proceedings would take place.
 

Paralyzed patient seeks millions

An Oregon man who was left paralyzed after undergoing surgery to address issues in his leg and foot has filed a large claim against both the hospital and surgical group involved in the procedure, details a story first reported by the Associated Press and picked up by other news outlets, including Fox12 Oregon.

On January 8, 2020, the man underwent brain surgery to address numbness in his left foot and a “vague” pain in his left leg. During the procedure, he experienced a dural tear, which the lead surgeon and his team addressed.

The following day, the man’s condition deteriorated, and he complained of severe pain, according to his lawsuit. Two days after his initial procedure, another surgeon performed a second procedure “to drain fluid and relieve pressure” on the patient’s brain. Nevertheless, the patient neither recovered sensation in his lower extremities nor use of his legs.

His claim against the facility and surgical practice asks for $43.5 million in damages for his injuries. For its part, the hospital expressed “deep compassion” for the patient and his family while making it clear that it believes its “caregivers provided excellent care.”

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

A jury last month found in favor of a West Virginia man who was permanently paralyzed following spinal cord surgery, according to a report by WOWK13 News, a local CBS affiliate in Huntington and Charleston, W. Va., among other news outlets.

On or about June 4, 2017, Michael Rodgers sustained injuries while riding his motorcycle. Admitted to Charleston Area Medical Center’s (CAMC’s) Level I trauma center, he initially showed no neurologic impairment and was able to feel and move all his extremities. A subsequent CT scan revealed, though, that he had incurred a T5 Chance fracture, as his later complaint states.

On June 6, a neurosurgeon affiliated with CAMC, John Orphanos, MD, instructed Mr. Rodgers to wear a back brace for 6 to 8 weeks. Later that day, though, Dr. Orphanos changed his course of treatment and recommended that Mr. Rodgers undergo surgery to treat his injuries. Despite his new recommendation, the neurosurgeon/spine specialist didn’t order a presurgical MRI of his patient’s thoracic spine. Typically, such a scan would have been used to determine any existing or potential spinal cord problems and any soft-tissue problems in the area of the fracture.

Not having such information, Dr. Orphanos was unaware that his patient had “an abundance of epidural fat, cord compression, cord edema, spinal abnormality, and spinal cord injury,” the complaint states. The neurosurgeon’s operative plan, therefore, included neither decompression of the spinal column nor use of neurophysiologic intraoperative monitoring, which is used to gauge, in real time during procedures, both how fast and how strongly a patient’s nerves are carrying signals.

Late on June 6, Dr. Orphanos performed a surgery to fuse his patient’s vertebrae from the T2 to the T6 region. Following the procedure, however, Mr. Rodgers experienced a complete loss of motor function and sensation in his lower extremities. A postoperative MRI proved inconclusive because of certain distorting effects of hardware implanted during the original surgery. Had a CT myelogram been ordered, it would have yielded a more accurate picture, the plaintiff alleged in his complaint.

Mr. Rodgers underwent a second surgery, during which Dr. Orphanos performed a T5 laminectomy. The patient’s loss of motor function and sensation persisted, however. He has been experiencing T5-level paraplegia ever since, with complete loss of control of his legs, bowel, and bladder.

In his complaint, Mr. Rodgers alleged that Dr. Orphanos had repeatedly deviated from the standard of care. Among other things, the plaintiff claimed, Dr. Orphanos had failed in both of his surgeries to order the proper preop and postop testing, thereby jeopardizing the outcomes of each procedure. This gross negligence and recklessness, the plaintiff argued, led directly to his permanent and disabling injuries.

Late last month, a West Virginia jury agreed that Dr. Orphanos was at fault and awarded Mr. Rodgers $17 million in damages.

Commented one of the pair of attorneys representing Mr. Rodgers: “We are very grateful to the jury, who saw through the attempts to rationalize the defendant’s conduct and delivered a jury verdict that will take care of Mr. Rodgers and provide the services he will need.”
 

Provider-to-provider disputes not time sensitive, state high court says

Early last month, Indiana’s high court ruled that the state’s med-mal statute of limitations doesn’t apply to disputes between providers, as a story in Radiology Business and other news sites reports.

The legal wrangling dates to April 2011. At that time, Joseph Shaughnessy underwent two CT scans at a Franciscan Alliance hospital, part of a healthcare system run by Franciscan Health. Outside radiologists from Lake Imaging read the scans, but they allegedly failed to note bleeding on the right side of the patient’s brain. Mr. Shaughnessy subsequently died, and his family filed suit against Franciscan, on the assumption that the radiologists were employees.

In 2015, the plaintiffs and Franciscan reached a $187,000 settlement, but Franciscan claimed it wasn’t liable for the payment, citing a clause in its prior agreement with Lake Imaging that protected it. But Lake Imaging sought to dismiss the Franciscan claim, arguing that the hospital system had failed to bring its suit within the state’s 2-year med-mal statute of limitations.

In its review of the case, the Indiana Supreme Court dismissed this argument: “(T)here is nothing in the [Medical Malpractice Act] to suggest that it extends beyond the physician-patient relationship to encompass commercial contracts between healthcare providers.”

In other words, while Indiana law places a 2-year limit on patients suing a hospital, doctor, or other healthcare professional, it places no such limit on contractually bound providers who take steps to sue each other.

As part of its unanimous decision, the high court also sent a claim by Lake Imaging against its insurance provider back to the trial court. The claim asks the insurance carrier — and not Lake Imaging — to assume responsibility for the settlement between Mr. Shaughnessy and Franciscan Alliance.

There was no word at press time as to when further legal proceedings would take place.
 

Paralyzed patient seeks millions

An Oregon man who was left paralyzed after undergoing surgery to address issues in his leg and foot has filed a large claim against both the hospital and surgical group involved in the procedure, details a story first reported by the Associated Press and picked up by other news outlets, including Fox12 Oregon.

On January 8, 2020, the man underwent brain surgery to address numbness in his left foot and a “vague” pain in his left leg. During the procedure, he experienced a dural tear, which the lead surgeon and his team addressed.

The following day, the man’s condition deteriorated, and he complained of severe pain, according to his lawsuit. Two days after his initial procedure, another surgeon performed a second procedure “to drain fluid and relieve pressure” on the patient’s brain. Nevertheless, the patient neither recovered sensation in his lower extremities nor use of his legs.

His claim against the facility and surgical practice asks for $43.5 million in damages for his injuries. For its part, the hospital expressed “deep compassion” for the patient and his family while making it clear that it believes its “caregivers provided excellent care.”

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

A jury last month found in favor of a West Virginia man who was permanently paralyzed following spinal cord surgery, according to a report by WOWK13 News, a local CBS affiliate in Huntington and Charleston, W. Va., among other news outlets.

On or about June 4, 2017, Michael Rodgers sustained injuries while riding his motorcycle. Admitted to Charleston Area Medical Center’s (CAMC’s) Level I trauma center, he initially showed no neurologic impairment and was able to feel and move all his extremities. A subsequent CT scan revealed, though, that he had incurred a T5 Chance fracture, as his later complaint states.

On June 6, a neurosurgeon affiliated with CAMC, John Orphanos, MD, instructed Mr. Rodgers to wear a back brace for 6 to 8 weeks. Later that day, though, Dr. Orphanos changed his course of treatment and recommended that Mr. Rodgers undergo surgery to treat his injuries. Despite his new recommendation, the neurosurgeon/spine specialist didn’t order a presurgical MRI of his patient’s thoracic spine. Typically, such a scan would have been used to determine any existing or potential spinal cord problems and any soft-tissue problems in the area of the fracture.

Not having such information, Dr. Orphanos was unaware that his patient had “an abundance of epidural fat, cord compression, cord edema, spinal abnormality, and spinal cord injury,” the complaint states. The neurosurgeon’s operative plan, therefore, included neither decompression of the spinal column nor use of neurophysiologic intraoperative monitoring, which is used to gauge, in real time during procedures, both how fast and how strongly a patient’s nerves are carrying signals.

Late on June 6, Dr. Orphanos performed a surgery to fuse his patient’s vertebrae from the T2 to the T6 region. Following the procedure, however, Mr. Rodgers experienced a complete loss of motor function and sensation in his lower extremities. A postoperative MRI proved inconclusive because of certain distorting effects of hardware implanted during the original surgery. Had a CT myelogram been ordered, it would have yielded a more accurate picture, the plaintiff alleged in his complaint.

Mr. Rodgers underwent a second surgery, during which Dr. Orphanos performed a T5 laminectomy. The patient’s loss of motor function and sensation persisted, however. He has been experiencing T5-level paraplegia ever since, with complete loss of control of his legs, bowel, and bladder.

In his complaint, Mr. Rodgers alleged that Dr. Orphanos had repeatedly deviated from the standard of care. Among other things, the plaintiff claimed, Dr. Orphanos had failed in both of his surgeries to order the proper preop and postop testing, thereby jeopardizing the outcomes of each procedure. This gross negligence and recklessness, the plaintiff argued, led directly to his permanent and disabling injuries.

Late last month, a West Virginia jury agreed that Dr. Orphanos was at fault and awarded Mr. Rodgers $17 million in damages.

Commented one of the pair of attorneys representing Mr. Rodgers: “We are very grateful to the jury, who saw through the attempts to rationalize the defendant’s conduct and delivered a jury verdict that will take care of Mr. Rodgers and provide the services he will need.”
 

Provider-to-provider disputes not time sensitive, state high court says

Early last month, Indiana’s high court ruled that the state’s med-mal statute of limitations doesn’t apply to disputes between providers, as a story in Radiology Business and other news sites reports.

The legal wrangling dates to April 2011. At that time, Joseph Shaughnessy underwent two CT scans at a Franciscan Alliance hospital, part of a healthcare system run by Franciscan Health. Outside radiologists from Lake Imaging read the scans, but they allegedly failed to note bleeding on the right side of the patient’s brain. Mr. Shaughnessy subsequently died, and his family filed suit against Franciscan, on the assumption that the radiologists were employees.

In 2015, the plaintiffs and Franciscan reached a $187,000 settlement, but Franciscan claimed it wasn’t liable for the payment, citing a clause in its prior agreement with Lake Imaging that protected it. But Lake Imaging sought to dismiss the Franciscan claim, arguing that the hospital system had failed to bring its suit within the state’s 2-year med-mal statute of limitations.

In its review of the case, the Indiana Supreme Court dismissed this argument: “(T)here is nothing in the [Medical Malpractice Act] to suggest that it extends beyond the physician-patient relationship to encompass commercial contracts between healthcare providers.”

In other words, while Indiana law places a 2-year limit on patients suing a hospital, doctor, or other healthcare professional, it places no such limit on contractually bound providers who take steps to sue each other.

As part of its unanimous decision, the high court also sent a claim by Lake Imaging against its insurance provider back to the trial court. The claim asks the insurance carrier — and not Lake Imaging — to assume responsibility for the settlement between Mr. Shaughnessy and Franciscan Alliance.

There was no word at press time as to when further legal proceedings would take place.
 

Paralyzed patient seeks millions

An Oregon man who was left paralyzed after undergoing surgery to address issues in his leg and foot has filed a large claim against both the hospital and surgical group involved in the procedure, details a story first reported by the Associated Press and picked up by other news outlets, including Fox12 Oregon.

On January 8, 2020, the man underwent brain surgery to address numbness in his left foot and a “vague” pain in his left leg. During the procedure, he experienced a dural tear, which the lead surgeon and his team addressed.

The following day, the man’s condition deteriorated, and he complained of severe pain, according to his lawsuit. Two days after his initial procedure, another surgeon performed a second procedure “to drain fluid and relieve pressure” on the patient’s brain. Nevertheless, the patient neither recovered sensation in his lower extremities nor use of his legs.

His claim against the facility and surgical practice asks for $43.5 million in damages for his injuries. For its part, the hospital expressed “deep compassion” for the patient and his family while making it clear that it believes its “caregivers provided excellent care.”

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

New research suggests that the casirivimab-imdevimab monoclonal antibody treatment for COVID-19 could have been delivered via injection instead of intravenously. There was no statistically significant difference in 28-day hospitalization or death in those treated intravenously and via subcutaneous injection.

The findings, published in JAMA Network Open, aren’t directly relevant at the moment, since the casirivimab-imdevimab treatment was abandoned when it failed to work during the Omicron outbreak. However, they point toward the importance of studying multiple routes of administration, said study lead author and pharmacist Erin K. McCreary, PharmD, of the University of Pittsburgh, in an interview.

“It would be beneficial for all future monoclonal antibodies for COVID-19 to be studied subcutaneously or intramuscularly, if possible, since that’s logistically easier than IV in the outpatient setting,” she said.

According to Dr. McCreary, an outpatient casirivimab-imdevimab treatment was used from 2020 to 2022 to treat higher-risk patients with mild to moderate COVID-19. The treatment was typically given intravenously as recommended by the federal government’s Emergency Use Authorization, she said. Clinical trials of the treatment, according to the study, allowed only IV administration.

“However, during the Delta surge, we were faced with so many patient referrals for treatment and staffing shortages that we couldn’t accommodate every patient unless we switched to [the] subcutaneous route,” Dr. McCreary said. This approach shortened appointment times by 30 minutes vs. infusion, she said.

There are many benefits to subcutaneous administration versus IV, Dr. McCreary said. “You don’t need to start an intravenous line, so you avoid the line kit and the nursing time needed for that. You draw up the drug directly into syringes and inject under the skin, so you avoid the need for a fluid bag to mix the drug in and run intravenously,” she said. “The appointment times are shorter, so you can accommodate more patients per day. Pharmacy interns can give subcutaneous injections, so you avoid the need for a nurse trained in placing intravenous lines.”

The researchers prospectively assigned 1,959 matched adults with mild to moderate COVID-19 to subcutaneous or intravenous treatment. Of 969 patients who received the subcutaneous treatment (mean age, 53.8; 56.4% women), the 28-day rate of hospitalization or death was 3.4%. Of 1,216 patients who received intravenous treatment (mean age, 54.3; 54.4% women), the rate was 1.7%. The difference was not statistically significant (P = .16).

Among 1,306 nontreated controls, 7.0% were hospitalized or died within 28 days (risk ratio = 0.48 vs. subcutaneous treatment group; 95% confidence interval, 0.30-0.80; P = .002).

“We did not find any patients where IV is a must,” Dr. McCreary said. “However, our study wasn’t powered to see a difference in certain subgroups.”

In an interview, University of Toronto internal medicine and pharmacology/toxicology physician Peter Wu, MD, said he agrees that the study has value because it emphasizes the importance of testing whether monoclonal antibodies can be administered in ways other than intravenously.

However, in the larger picture, he said, this may be irrelevant since it’s clear that anti-spike treatments are not holding up against COVID-19 variants.

No study funding is reported. Some study authors reported disclosures outside the submitted work. Dr. Wu has disclosed no relevant financial relationships.

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

New research suggests that the casirivimab-imdevimab monoclonal antibody treatment for COVID-19 could have been delivered via injection instead of intravenously. There was no statistically significant difference in 28-day hospitalization or death in those treated intravenously and via subcutaneous injection.

The findings, published in JAMA Network Open, aren’t directly relevant at the moment, since the casirivimab-imdevimab treatment was abandoned when it failed to work during the Omicron outbreak. However, they point toward the importance of studying multiple routes of administration, said study lead author and pharmacist Erin K. McCreary, PharmD, of the University of Pittsburgh, in an interview.

“It would be beneficial for all future monoclonal antibodies for COVID-19 to be studied subcutaneously or intramuscularly, if possible, since that’s logistically easier than IV in the outpatient setting,” she said.

According to Dr. McCreary, an outpatient casirivimab-imdevimab treatment was used from 2020 to 2022 to treat higher-risk patients with mild to moderate COVID-19. The treatment was typically given intravenously as recommended by the federal government’s Emergency Use Authorization, she said. Clinical trials of the treatment, according to the study, allowed only IV administration.

“However, during the Delta surge, we were faced with so many patient referrals for treatment and staffing shortages that we couldn’t accommodate every patient unless we switched to [the] subcutaneous route,” Dr. McCreary said. This approach shortened appointment times by 30 minutes vs. infusion, she said.

There are many benefits to subcutaneous administration versus IV, Dr. McCreary said. “You don’t need to start an intravenous line, so you avoid the line kit and the nursing time needed for that. You draw up the drug directly into syringes and inject under the skin, so you avoid the need for a fluid bag to mix the drug in and run intravenously,” she said. “The appointment times are shorter, so you can accommodate more patients per day. Pharmacy interns can give subcutaneous injections, so you avoid the need for a nurse trained in placing intravenous lines.”

The researchers prospectively assigned 1,959 matched adults with mild to moderate COVID-19 to subcutaneous or intravenous treatment. Of 969 patients who received the subcutaneous treatment (mean age, 53.8; 56.4% women), the 28-day rate of hospitalization or death was 3.4%. Of 1,216 patients who received intravenous treatment (mean age, 54.3; 54.4% women), the rate was 1.7%. The difference was not statistically significant (P = .16).

Among 1,306 nontreated controls, 7.0% were hospitalized or died within 28 days (risk ratio = 0.48 vs. subcutaneous treatment group; 95% confidence interval, 0.30-0.80; P = .002).

“We did not find any patients where IV is a must,” Dr. McCreary said. “However, our study wasn’t powered to see a difference in certain subgroups.”

In an interview, University of Toronto internal medicine and pharmacology/toxicology physician Peter Wu, MD, said he agrees that the study has value because it emphasizes the importance of testing whether monoclonal antibodies can be administered in ways other than intravenously.

However, in the larger picture, he said, this may be irrelevant since it’s clear that anti-spike treatments are not holding up against COVID-19 variants.

No study funding is reported. Some study authors reported disclosures outside the submitted work. Dr. Wu has disclosed no relevant financial relationships.

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

New research suggests that the casirivimab-imdevimab monoclonal antibody treatment for COVID-19 could have been delivered via injection instead of intravenously. There was no statistically significant difference in 28-day hospitalization or death in those treated intravenously and via subcutaneous injection.

The findings, published in JAMA Network Open, aren’t directly relevant at the moment, since the casirivimab-imdevimab treatment was abandoned when it failed to work during the Omicron outbreak. However, they point toward the importance of studying multiple routes of administration, said study lead author and pharmacist Erin K. McCreary, PharmD, of the University of Pittsburgh, in an interview.

“It would be beneficial for all future monoclonal antibodies for COVID-19 to be studied subcutaneously or intramuscularly, if possible, since that’s logistically easier than IV in the outpatient setting,” she said.

According to Dr. McCreary, an outpatient casirivimab-imdevimab treatment was used from 2020 to 2022 to treat higher-risk patients with mild to moderate COVID-19. The treatment was typically given intravenously as recommended by the federal government’s Emergency Use Authorization, she said. Clinical trials of the treatment, according to the study, allowed only IV administration.

“However, during the Delta surge, we were faced with so many patient referrals for treatment and staffing shortages that we couldn’t accommodate every patient unless we switched to [the] subcutaneous route,” Dr. McCreary said. This approach shortened appointment times by 30 minutes vs. infusion, she said.

There are many benefits to subcutaneous administration versus IV, Dr. McCreary said. “You don’t need to start an intravenous line, so you avoid the line kit and the nursing time needed for that. You draw up the drug directly into syringes and inject under the skin, so you avoid the need for a fluid bag to mix the drug in and run intravenously,” she said. “The appointment times are shorter, so you can accommodate more patients per day. Pharmacy interns can give subcutaneous injections, so you avoid the need for a nurse trained in placing intravenous lines.”

The researchers prospectively assigned 1,959 matched adults with mild to moderate COVID-19 to subcutaneous or intravenous treatment. Of 969 patients who received the subcutaneous treatment (mean age, 53.8; 56.4% women), the 28-day rate of hospitalization or death was 3.4%. Of 1,216 patients who received intravenous treatment (mean age, 54.3; 54.4% women), the rate was 1.7%. The difference was not statistically significant (P = .16).

Among 1,306 nontreated controls, 7.0% were hospitalized or died within 28 days (risk ratio = 0.48 vs. subcutaneous treatment group; 95% confidence interval, 0.30-0.80; P = .002).

“We did not find any patients where IV is a must,” Dr. McCreary said. “However, our study wasn’t powered to see a difference in certain subgroups.”

In an interview, University of Toronto internal medicine and pharmacology/toxicology physician Peter Wu, MD, said he agrees that the study has value because it emphasizes the importance of testing whether monoclonal antibodies can be administered in ways other than intravenously.

However, in the larger picture, he said, this may be irrelevant since it’s clear that anti-spike treatments are not holding up against COVID-19 variants.

No study funding is reported. Some study authors reported disclosures outside the submitted work. Dr. Wu has disclosed no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

At 32 years old, the world was at Larry Unger’s feet. He was vice president at one of Wall Street’s most successful investment management firms, selling mutual funds to more than 1,000 brokers across New York. His clients relied on him for good advice, great jokes, and superlative Yankees tickets. His recent memories included fraternity days at Cornell University and a Harvard law degree. His childhood on the Lower East Side was behind him. He had his own apartment and a beautiful girlfriend.

Then his back started hurting, and he was drenched in sweat at night. His physician suggested it was a basketball injury. Weeks of tests followed, and he changed doctors. Mr. Unger met with an oncologist at Memorial Sloan Kettering Cancer Center who wouldn’t let him go home after the appointment. The next day brought exploratory surgery and an answer to all the questions.

courtesy of Larry Unger

Mr. Unger was diagnosed with stage IIIB Hodgkin lymphoma.

Thirty years later, Mr. Unger credited his survival to the late Subhash Gulati, MD, PhD, then MSKCC’s director of stem cell transplantation. He still recalls Dr. Gulati’s words to him: “Radical situations call for radical solutions.” In 1992, that “radical solution” was an autologous bone-marrow transplant.

“Mr. Unger was a patient pioneer,” said Kenneth Offit, MD, another MSKCC oncologist who also cared for him at that time.

To mark the 30th anniversary of Larry’s pioneering transplant, this news organization compared treatments for Hodgkin disease then and now – a revolutionary change that some hematologist/oncologists consider among the great successes in their field.
 

Transplantation for Hodgkin: The early 90s

Hodgkin lymphoma is fairly rare, accounting for just 0.5% of all cancers and 15% of lymphomas. It tends to target young, male adults like Mr. Unger. Today 88% of patients with Hodgkin survive at least 5 years.

When Dr. Gulati offered Mr. Unger his “radical solution” 3 decades ago, the idea of autologous bone marrow transplantation in Hodgkin lymphoma was not new. The first attempt appeared in the literature in the 1950s, but it was still unclear how patients could survive the procedure. It involved destroying the patient’s own immune system prior to the transplant, a huge risk in itself. Worse, the patient was pummeled with chemotherapy and/or radiation to clear out the cancerous bone marrow – a process called “conditioning.”

However, throughout the 1980s, MSKCC had been running clinical trials to perfect the conditioning mix, so by 1992 Dr. Gulati was well-placed to help Mr. Unger.

It is unclear what conditioning Mr. Unger received because his records were not made available. However, around the time that Mr. Unger underwent his transplant, Dr. Gulati and colleagues published the conditioning regimens in use at MSKCC. Patients with refractory or relapsed Hodgkin disease received a conditioning mix of total nodal irradiation (TNI), etoposide (Vepesid) and cyclophosphamide. Patients who had already been through radiotherapy were given carmustine instead of TNI.

In that early publication, Dr. Gulati and the MSKCC team reported 0 “toxic deaths” with the TNI mix, and at the 2-year point 75% of the patients were still alive (n = 28). Patients who had already received radiation treatment did less well, with 55% survival at 2 years, at a cost of 14% toxic deaths (n = 22).
 

Mr. Unger’s experience, 30 years ago

According to Mr. Unger, the initial treatment for his stage IIIB Hodgkin lymphoma was MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone) plus ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine).

“They wanted to give me two chemo programs at once because they said I was very sick,” Mr. Unger recalled. “I wound up staying in the hospital quite a bit because every time I got these [treatments] I’d get a fever. This went on for month after month after month. Finally, they said: ‘The tumors are starting to shrink. ... I want you to meet Dr. Gulati.’ ”

Mr. Unger said that Dr. Gulati told him: “There is another procedure called the bone marrow transplant which we’ve been doing. This would be like hitting it with a nuclear weapon. We would really wipe it out and make sure that you never come back.”

The alternative was high-dose radiotherapy. However, Dr. Gulati shared MSKCC’s hard-won knowledge that an autologous transplant was less successful after radiation. Dr. Gulati also told Mr. Unger that surgery was needed before the transplant: a laparotomy to restage his tumors.

After discussing the situation with his father, Mr. Unger decided to undergo the transplant.

The night before treatment started, he was laughing and joking with a friend in his room at MSKCC. The next day, the laughing stopped. The conditioning, he said, “was harrowing beyond belief ... 100 times worse than the chemo.”

Chemotherapy came first, followed 2 days later by radiation, presumably TNI. Mr. Unger experienced constant vomiting, intraocular bleeding and high fevers; the soft tissue of his throat “fell apart,” he said.

“I couldn’t move. It was like being dead,” he said. “Finally, maybe after a month or so, I could finally have a little water.” Mr. Unger said his immune system took 6-8 weeks to recover. He concluded, with heroic understatement, “it was rough.”

The battle against Hodgkin was over, but fallout from the chemotherapy lingered. Although Mr. Unger was able to return to his family and the job he loved, in the following years he was never entirely well. He contracted shingles soon after his transplant, then diabetes within 15 years. A heart attack followed in 2008 then, in 2015, an autoimmune disease that still affects his mobility.

However, Mr. Unger remains grateful: “The fact that we did these cutting-edge techniques with me got me to the point where – although I had some problems afterward, and I have problems now – it gave me well over 30 years of a really great life.”

“There are a lot of good doctors out there,” he added. “Some of them go to extraordinary lengths to help people. I try to do the same with the extra 30 years I’ve been given, try to be nice to people and make people feel good. I don’t really see any other reason to be on earth.”
 

Treatment for Hodgkin lymphoma: 2022

For a comparison of Mr. Unger’s experience with the current approach to Hodgkin lymphoma, this news organization spoke to Miguel-Angel Perales, MD, current chief of the adult bone marrow transplant service at MSKCC. Although Dr. Perales could not comment specifically on Mr. Unger’s case without his records, Dr. Perales was able to review the revolutions in treatment for all patients over the past 30 years.

Courtesy MSKCC

Certainly, physicians no longer need to inflict a laparotomy on patients just to stage the disease, Dr. Perales said. “This sounds barbaric today. Nowadays we have PET scans.”

Another key change, Dr. Perales said, is in the up-front management of the disease.

For example, MOPP “is going back to the prehistory of chemotherapy,” Dr. Perales said. He was not surprised to learn that Mr. Unger later developed complications such as diabetes and heart disease.

“We’ve completely revolutionized the treatment,” Dr. Perales said. “We [now] use combinations that are much less toxic than MOPP, [and] we’re curing more patients up front.” Treatment is tailored by stage and the likelihood of response to therapy. Aggressive approaches are reserved for patients more likely to fail treatment.

Pretransplant conditioning has also changed for the better, with less toxicity and fewer long-term complications. Total body irradiation has “fallen by the wayside,” said Dr. Perales. Instead, patients get BEAM, a combination of carmustine, etoposide, cytarabine (Cytosar-U, Ara-C), and melphalan (Alkeran), 1 week before the transplant.

Perhaps the most profound change, which began in the 1990s shortly after Larry’s transplant, was that peripheral-blood stem cells gradually replaced bone marrow for both autologous and allogeneic transplant. In 2022, nearly all autologous transplants use peripheral-blood stem cells.

Instead of onerous bone-marrow aspiration in the operating room, the stem cells are collected from the patient’s blood. First, the patient’s bone marrow is hyperstimulated with high doses of filgrastim (G-CSF, Neupogen, Granix) for several days. Stem cells spill into the patient’s blood. Once blood is collected from the patient, the stem cells are separated and stored ready for the transplant. (In theory, stem cell products are “cancer free”; in practice there may be some contaminating cells, said Dr. Perales.)

Nowadays “transplanting” the stem cells back into the body bears no relation to what happened in 1992. The stem-cell infusion is typically an outpatient procedure, and one-third of patients may never be admitted to the hospital at all.

In contrast to Mr. Unger’s excruciating 8-week hospital stay, immune recovery currently takes 12-14 days, often entirely in the patient’s own home, with the option of extra filgrastim to speed things up.

Despite these profound changes, said Dr. Perales, the real quantum leap has occurred post transplant.

In 2015, a multinational team led by MSKCC’s Dr. Craig Moskowitz published a trial in the Lancet showing that brentuximab vedotin halved the risk of relapse after autologous transplantation in high-risk Hodgkin lymphoma patients versus placebo (hazard ratio, 0.57; P = .0013; n = 329). The CD30-directed antibody-drug conjugate was so successful that the placebo patients were encouraged to cross over into the treatment group; many of them were salvaged.

As a result, Dr. Perales said, brentuximab vedotin has now become the standard in high-risk Hodgkin patients following a transplant.

The checkpoint inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) have also been “transformational” in Hodgkin lymphoma, Dr. Perales said. He explained that Hodgkin lymphoma is “exquisitely sensitive” to these therapies because the disease expresses high levels of the binding proteins for these drugs. This allows the immunotherapies to hit both the immune system and the disease.

Most cancers have response rates for checkpoint inhibitors below 40%, according to a recent analysis by Anas Younes, former chief of lymphoma at MSKCC, and his colleague Eri Matsuki, then a visiting fellow. By contrast, in Hodgkin lymphoma response to these drugs is 66%-87%.

Dr. Perales said: “It tells you how effective these drugs are, that we could move from somebody getting MOPP, which is like throwing a nuclear bomb at somebody, to a combination of two drugs that can easily be given out-patient and that have very little, if any, side effects.”
 

The future: No chemo, no transplants?

“One of the holy grails in Hodgkin would be if we could treat patients with the combination of a checkpoint inhibitor and brentuximab and what is being termed the ‘chemotherapy-free’ approach to Hodgkin disease,” said Dr. Perales.

What else remains to be done in the world of transplants for Hodgkin lymphoma?

Dr. Perales didn’t hesitate: “To eliminate the need for them. If we can have better targeted therapy up front that cures more patients, then we never even have to consider transplant. Basically, to put me out of work. I’m sure I’ll find other things to do.”

The current treatment of Hodgkin lymphoma “is really what we all consider one of the successes in oncology,” said Dr. Perales. “It’s a beautiful story.”

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serves on data and safety monitoring boards for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serves on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

At 32 years old, the world was at Larry Unger’s feet. He was vice president at one of Wall Street’s most successful investment management firms, selling mutual funds to more than 1,000 brokers across New York. His clients relied on him for good advice, great jokes, and superlative Yankees tickets. His recent memories included fraternity days at Cornell University and a Harvard law degree. His childhood on the Lower East Side was behind him. He had his own apartment and a beautiful girlfriend.

Then his back started hurting, and he was drenched in sweat at night. His physician suggested it was a basketball injury. Weeks of tests followed, and he changed doctors. Mr. Unger met with an oncologist at Memorial Sloan Kettering Cancer Center who wouldn’t let him go home after the appointment. The next day brought exploratory surgery and an answer to all the questions.

courtesy of Larry Unger

Mr. Unger was diagnosed with stage IIIB Hodgkin lymphoma.

Thirty years later, Mr. Unger credited his survival to the late Subhash Gulati, MD, PhD, then MSKCC’s director of stem cell transplantation. He still recalls Dr. Gulati’s words to him: “Radical situations call for radical solutions.” In 1992, that “radical solution” was an autologous bone-marrow transplant.

“Mr. Unger was a patient pioneer,” said Kenneth Offit, MD, another MSKCC oncologist who also cared for him at that time.

To mark the 30th anniversary of Larry’s pioneering transplant, this news organization compared treatments for Hodgkin disease then and now – a revolutionary change that some hematologist/oncologists consider among the great successes in their field.
 

Transplantation for Hodgkin: The early 90s

Hodgkin lymphoma is fairly rare, accounting for just 0.5% of all cancers and 15% of lymphomas. It tends to target young, male adults like Mr. Unger. Today 88% of patients with Hodgkin survive at least 5 years.

When Dr. Gulati offered Mr. Unger his “radical solution” 3 decades ago, the idea of autologous bone marrow transplantation in Hodgkin lymphoma was not new. The first attempt appeared in the literature in the 1950s, but it was still unclear how patients could survive the procedure. It involved destroying the patient’s own immune system prior to the transplant, a huge risk in itself. Worse, the patient was pummeled with chemotherapy and/or radiation to clear out the cancerous bone marrow – a process called “conditioning.”

However, throughout the 1980s, MSKCC had been running clinical trials to perfect the conditioning mix, so by 1992 Dr. Gulati was well-placed to help Mr. Unger.

It is unclear what conditioning Mr. Unger received because his records were not made available. However, around the time that Mr. Unger underwent his transplant, Dr. Gulati and colleagues published the conditioning regimens in use at MSKCC. Patients with refractory or relapsed Hodgkin disease received a conditioning mix of total nodal irradiation (TNI), etoposide (Vepesid) and cyclophosphamide. Patients who had already been through radiotherapy were given carmustine instead of TNI.

In that early publication, Dr. Gulati and the MSKCC team reported 0 “toxic deaths” with the TNI mix, and at the 2-year point 75% of the patients were still alive (n = 28). Patients who had already received radiation treatment did less well, with 55% survival at 2 years, at a cost of 14% toxic deaths (n = 22).
 

Mr. Unger’s experience, 30 years ago

According to Mr. Unger, the initial treatment for his stage IIIB Hodgkin lymphoma was MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone) plus ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine).

“They wanted to give me two chemo programs at once because they said I was very sick,” Mr. Unger recalled. “I wound up staying in the hospital quite a bit because every time I got these [treatments] I’d get a fever. This went on for month after month after month. Finally, they said: ‘The tumors are starting to shrink. ... I want you to meet Dr. Gulati.’ ”

Mr. Unger said that Dr. Gulati told him: “There is another procedure called the bone marrow transplant which we’ve been doing. This would be like hitting it with a nuclear weapon. We would really wipe it out and make sure that you never come back.”

The alternative was high-dose radiotherapy. However, Dr. Gulati shared MSKCC’s hard-won knowledge that an autologous transplant was less successful after radiation. Dr. Gulati also told Mr. Unger that surgery was needed before the transplant: a laparotomy to restage his tumors.

After discussing the situation with his father, Mr. Unger decided to undergo the transplant.

The night before treatment started, he was laughing and joking with a friend in his room at MSKCC. The next day, the laughing stopped. The conditioning, he said, “was harrowing beyond belief ... 100 times worse than the chemo.”

Chemotherapy came first, followed 2 days later by radiation, presumably TNI. Mr. Unger experienced constant vomiting, intraocular bleeding and high fevers; the soft tissue of his throat “fell apart,” he said.

“I couldn’t move. It was like being dead,” he said. “Finally, maybe after a month or so, I could finally have a little water.” Mr. Unger said his immune system took 6-8 weeks to recover. He concluded, with heroic understatement, “it was rough.”

The battle against Hodgkin was over, but fallout from the chemotherapy lingered. Although Mr. Unger was able to return to his family and the job he loved, in the following years he was never entirely well. He contracted shingles soon after his transplant, then diabetes within 15 years. A heart attack followed in 2008 then, in 2015, an autoimmune disease that still affects his mobility.

However, Mr. Unger remains grateful: “The fact that we did these cutting-edge techniques with me got me to the point where – although I had some problems afterward, and I have problems now – it gave me well over 30 years of a really great life.”

“There are a lot of good doctors out there,” he added. “Some of them go to extraordinary lengths to help people. I try to do the same with the extra 30 years I’ve been given, try to be nice to people and make people feel good. I don’t really see any other reason to be on earth.”
 

Treatment for Hodgkin lymphoma: 2022

For a comparison of Mr. Unger’s experience with the current approach to Hodgkin lymphoma, this news organization spoke to Miguel-Angel Perales, MD, current chief of the adult bone marrow transplant service at MSKCC. Although Dr. Perales could not comment specifically on Mr. Unger’s case without his records, Dr. Perales was able to review the revolutions in treatment for all patients over the past 30 years.

Courtesy MSKCC

Certainly, physicians no longer need to inflict a laparotomy on patients just to stage the disease, Dr. Perales said. “This sounds barbaric today. Nowadays we have PET scans.”

Another key change, Dr. Perales said, is in the up-front management of the disease.

For example, MOPP “is going back to the prehistory of chemotherapy,” Dr. Perales said. He was not surprised to learn that Mr. Unger later developed complications such as diabetes and heart disease.

“We’ve completely revolutionized the treatment,” Dr. Perales said. “We [now] use combinations that are much less toxic than MOPP, [and] we’re curing more patients up front.” Treatment is tailored by stage and the likelihood of response to therapy. Aggressive approaches are reserved for patients more likely to fail treatment.

Pretransplant conditioning has also changed for the better, with less toxicity and fewer long-term complications. Total body irradiation has “fallen by the wayside,” said Dr. Perales. Instead, patients get BEAM, a combination of carmustine, etoposide, cytarabine (Cytosar-U, Ara-C), and melphalan (Alkeran), 1 week before the transplant.

Perhaps the most profound change, which began in the 1990s shortly after Larry’s transplant, was that peripheral-blood stem cells gradually replaced bone marrow for both autologous and allogeneic transplant. In 2022, nearly all autologous transplants use peripheral-blood stem cells.

Instead of onerous bone-marrow aspiration in the operating room, the stem cells are collected from the patient’s blood. First, the patient’s bone marrow is hyperstimulated with high doses of filgrastim (G-CSF, Neupogen, Granix) for several days. Stem cells spill into the patient’s blood. Once blood is collected from the patient, the stem cells are separated and stored ready for the transplant. (In theory, stem cell products are “cancer free”; in practice there may be some contaminating cells, said Dr. Perales.)

Nowadays “transplanting” the stem cells back into the body bears no relation to what happened in 1992. The stem-cell infusion is typically an outpatient procedure, and one-third of patients may never be admitted to the hospital at all.

In contrast to Mr. Unger’s excruciating 8-week hospital stay, immune recovery currently takes 12-14 days, often entirely in the patient’s own home, with the option of extra filgrastim to speed things up.

Despite these profound changes, said Dr. Perales, the real quantum leap has occurred post transplant.

In 2015, a multinational team led by MSKCC’s Dr. Craig Moskowitz published a trial in the Lancet showing that brentuximab vedotin halved the risk of relapse after autologous transplantation in high-risk Hodgkin lymphoma patients versus placebo (hazard ratio, 0.57; P = .0013; n = 329). The CD30-directed antibody-drug conjugate was so successful that the placebo patients were encouraged to cross over into the treatment group; many of them were salvaged.

As a result, Dr. Perales said, brentuximab vedotin has now become the standard in high-risk Hodgkin patients following a transplant.

The checkpoint inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) have also been “transformational” in Hodgkin lymphoma, Dr. Perales said. He explained that Hodgkin lymphoma is “exquisitely sensitive” to these therapies because the disease expresses high levels of the binding proteins for these drugs. This allows the immunotherapies to hit both the immune system and the disease.

Most cancers have response rates for checkpoint inhibitors below 40%, according to a recent analysis by Anas Younes, former chief of lymphoma at MSKCC, and his colleague Eri Matsuki, then a visiting fellow. By contrast, in Hodgkin lymphoma response to these drugs is 66%-87%.

Dr. Perales said: “It tells you how effective these drugs are, that we could move from somebody getting MOPP, which is like throwing a nuclear bomb at somebody, to a combination of two drugs that can easily be given out-patient and that have very little, if any, side effects.”
 

The future: No chemo, no transplants?

“One of the holy grails in Hodgkin would be if we could treat patients with the combination of a checkpoint inhibitor and brentuximab and what is being termed the ‘chemotherapy-free’ approach to Hodgkin disease,” said Dr. Perales.

What else remains to be done in the world of transplants for Hodgkin lymphoma?

Dr. Perales didn’t hesitate: “To eliminate the need for them. If we can have better targeted therapy up front that cures more patients, then we never even have to consider transplant. Basically, to put me out of work. I’m sure I’ll find other things to do.”

The current treatment of Hodgkin lymphoma “is really what we all consider one of the successes in oncology,” said Dr. Perales. “It’s a beautiful story.”

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serves on data and safety monitoring boards for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serves on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

At 32 years old, the world was at Larry Unger’s feet. He was vice president at one of Wall Street’s most successful investment management firms, selling mutual funds to more than 1,000 brokers across New York. His clients relied on him for good advice, great jokes, and superlative Yankees tickets. His recent memories included fraternity days at Cornell University and a Harvard law degree. His childhood on the Lower East Side was behind him. He had his own apartment and a beautiful girlfriend.

Then his back started hurting, and he was drenched in sweat at night. His physician suggested it was a basketball injury. Weeks of tests followed, and he changed doctors. Mr. Unger met with an oncologist at Memorial Sloan Kettering Cancer Center who wouldn’t let him go home after the appointment. The next day brought exploratory surgery and an answer to all the questions.

courtesy of Larry Unger

Mr. Unger was diagnosed with stage IIIB Hodgkin lymphoma.

Thirty years later, Mr. Unger credited his survival to the late Subhash Gulati, MD, PhD, then MSKCC’s director of stem cell transplantation. He still recalls Dr. Gulati’s words to him: “Radical situations call for radical solutions.” In 1992, that “radical solution” was an autologous bone-marrow transplant.

“Mr. Unger was a patient pioneer,” said Kenneth Offit, MD, another MSKCC oncologist who also cared for him at that time.

To mark the 30th anniversary of Larry’s pioneering transplant, this news organization compared treatments for Hodgkin disease then and now – a revolutionary change that some hematologist/oncologists consider among the great successes in their field.
 

Transplantation for Hodgkin: The early 90s

Hodgkin lymphoma is fairly rare, accounting for just 0.5% of all cancers and 15% of lymphomas. It tends to target young, male adults like Mr. Unger. Today 88% of patients with Hodgkin survive at least 5 years.

When Dr. Gulati offered Mr. Unger his “radical solution” 3 decades ago, the idea of autologous bone marrow transplantation in Hodgkin lymphoma was not new. The first attempt appeared in the literature in the 1950s, but it was still unclear how patients could survive the procedure. It involved destroying the patient’s own immune system prior to the transplant, a huge risk in itself. Worse, the patient was pummeled with chemotherapy and/or radiation to clear out the cancerous bone marrow – a process called “conditioning.”

However, throughout the 1980s, MSKCC had been running clinical trials to perfect the conditioning mix, so by 1992 Dr. Gulati was well-placed to help Mr. Unger.

It is unclear what conditioning Mr. Unger received because his records were not made available. However, around the time that Mr. Unger underwent his transplant, Dr. Gulati and colleagues published the conditioning regimens in use at MSKCC. Patients with refractory or relapsed Hodgkin disease received a conditioning mix of total nodal irradiation (TNI), etoposide (Vepesid) and cyclophosphamide. Patients who had already been through radiotherapy were given carmustine instead of TNI.

In that early publication, Dr. Gulati and the MSKCC team reported 0 “toxic deaths” with the TNI mix, and at the 2-year point 75% of the patients were still alive (n = 28). Patients who had already received radiation treatment did less well, with 55% survival at 2 years, at a cost of 14% toxic deaths (n = 22).
 

Mr. Unger’s experience, 30 years ago

According to Mr. Unger, the initial treatment for his stage IIIB Hodgkin lymphoma was MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone) plus ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine).

“They wanted to give me two chemo programs at once because they said I was very sick,” Mr. Unger recalled. “I wound up staying in the hospital quite a bit because every time I got these [treatments] I’d get a fever. This went on for month after month after month. Finally, they said: ‘The tumors are starting to shrink. ... I want you to meet Dr. Gulati.’ ”

Mr. Unger said that Dr. Gulati told him: “There is another procedure called the bone marrow transplant which we’ve been doing. This would be like hitting it with a nuclear weapon. We would really wipe it out and make sure that you never come back.”

The alternative was high-dose radiotherapy. However, Dr. Gulati shared MSKCC’s hard-won knowledge that an autologous transplant was less successful after radiation. Dr. Gulati also told Mr. Unger that surgery was needed before the transplant: a laparotomy to restage his tumors.

After discussing the situation with his father, Mr. Unger decided to undergo the transplant.

The night before treatment started, he was laughing and joking with a friend in his room at MSKCC. The next day, the laughing stopped. The conditioning, he said, “was harrowing beyond belief ... 100 times worse than the chemo.”

Chemotherapy came first, followed 2 days later by radiation, presumably TNI. Mr. Unger experienced constant vomiting, intraocular bleeding and high fevers; the soft tissue of his throat “fell apart,” he said.

“I couldn’t move. It was like being dead,” he said. “Finally, maybe after a month or so, I could finally have a little water.” Mr. Unger said his immune system took 6-8 weeks to recover. He concluded, with heroic understatement, “it was rough.”

The battle against Hodgkin was over, but fallout from the chemotherapy lingered. Although Mr. Unger was able to return to his family and the job he loved, in the following years he was never entirely well. He contracted shingles soon after his transplant, then diabetes within 15 years. A heart attack followed in 2008 then, in 2015, an autoimmune disease that still affects his mobility.

However, Mr. Unger remains grateful: “The fact that we did these cutting-edge techniques with me got me to the point where – although I had some problems afterward, and I have problems now – it gave me well over 30 years of a really great life.”

“There are a lot of good doctors out there,” he added. “Some of them go to extraordinary lengths to help people. I try to do the same with the extra 30 years I’ve been given, try to be nice to people and make people feel good. I don’t really see any other reason to be on earth.”
 

Treatment for Hodgkin lymphoma: 2022

For a comparison of Mr. Unger’s experience with the current approach to Hodgkin lymphoma, this news organization spoke to Miguel-Angel Perales, MD, current chief of the adult bone marrow transplant service at MSKCC. Although Dr. Perales could not comment specifically on Mr. Unger’s case without his records, Dr. Perales was able to review the revolutions in treatment for all patients over the past 30 years.

Courtesy MSKCC

Certainly, physicians no longer need to inflict a laparotomy on patients just to stage the disease, Dr. Perales said. “This sounds barbaric today. Nowadays we have PET scans.”

Another key change, Dr. Perales said, is in the up-front management of the disease.

For example, MOPP “is going back to the prehistory of chemotherapy,” Dr. Perales said. He was not surprised to learn that Mr. Unger later developed complications such as diabetes and heart disease.

“We’ve completely revolutionized the treatment,” Dr. Perales said. “We [now] use combinations that are much less toxic than MOPP, [and] we’re curing more patients up front.” Treatment is tailored by stage and the likelihood of response to therapy. Aggressive approaches are reserved for patients more likely to fail treatment.

Pretransplant conditioning has also changed for the better, with less toxicity and fewer long-term complications. Total body irradiation has “fallen by the wayside,” said Dr. Perales. Instead, patients get BEAM, a combination of carmustine, etoposide, cytarabine (Cytosar-U, Ara-C), and melphalan (Alkeran), 1 week before the transplant.

Perhaps the most profound change, which began in the 1990s shortly after Larry’s transplant, was that peripheral-blood stem cells gradually replaced bone marrow for both autologous and allogeneic transplant. In 2022, nearly all autologous transplants use peripheral-blood stem cells.

Instead of onerous bone-marrow aspiration in the operating room, the stem cells are collected from the patient’s blood. First, the patient’s bone marrow is hyperstimulated with high doses of filgrastim (G-CSF, Neupogen, Granix) for several days. Stem cells spill into the patient’s blood. Once blood is collected from the patient, the stem cells are separated and stored ready for the transplant. (In theory, stem cell products are “cancer free”; in practice there may be some contaminating cells, said Dr. Perales.)

Nowadays “transplanting” the stem cells back into the body bears no relation to what happened in 1992. The stem-cell infusion is typically an outpatient procedure, and one-third of patients may never be admitted to the hospital at all.

In contrast to Mr. Unger’s excruciating 8-week hospital stay, immune recovery currently takes 12-14 days, often entirely in the patient’s own home, with the option of extra filgrastim to speed things up.

Despite these profound changes, said Dr. Perales, the real quantum leap has occurred post transplant.

In 2015, a multinational team led by MSKCC’s Dr. Craig Moskowitz published a trial in the Lancet showing that brentuximab vedotin halved the risk of relapse after autologous transplantation in high-risk Hodgkin lymphoma patients versus placebo (hazard ratio, 0.57; P = .0013; n = 329). The CD30-directed antibody-drug conjugate was so successful that the placebo patients were encouraged to cross over into the treatment group; many of them were salvaged.

As a result, Dr. Perales said, brentuximab vedotin has now become the standard in high-risk Hodgkin patients following a transplant.

The checkpoint inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) have also been “transformational” in Hodgkin lymphoma, Dr. Perales said. He explained that Hodgkin lymphoma is “exquisitely sensitive” to these therapies because the disease expresses high levels of the binding proteins for these drugs. This allows the immunotherapies to hit both the immune system and the disease.

Most cancers have response rates for checkpoint inhibitors below 40%, according to a recent analysis by Anas Younes, former chief of lymphoma at MSKCC, and his colleague Eri Matsuki, then a visiting fellow. By contrast, in Hodgkin lymphoma response to these drugs is 66%-87%.

Dr. Perales said: “It tells you how effective these drugs are, that we could move from somebody getting MOPP, which is like throwing a nuclear bomb at somebody, to a combination of two drugs that can easily be given out-patient and that have very little, if any, side effects.”
 

The future: No chemo, no transplants?

“One of the holy grails in Hodgkin would be if we could treat patients with the combination of a checkpoint inhibitor and brentuximab and what is being termed the ‘chemotherapy-free’ approach to Hodgkin disease,” said Dr. Perales.

What else remains to be done in the world of transplants for Hodgkin lymphoma?

Dr. Perales didn’t hesitate: “To eliminate the need for them. If we can have better targeted therapy up front that cures more patients, then we never even have to consider transplant. Basically, to put me out of work. I’m sure I’ll find other things to do.”

The current treatment of Hodgkin lymphoma “is really what we all consider one of the successes in oncology,” said Dr. Perales. “It’s a beautiful story.”

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serves on data and safety monitoring boards for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serves on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

No need to ‘guess what size horse you are’

Is COVID-19 warming up for yet another surge? Maybe. That means it’s also time for the return of its remora-like follower, ivermectin. Our thanks go out to the Tennessee state legislature for bringing the proven-to-be-ineffective treatment for COVID back into our hearts and minds and emergency rooms.

StockPlanets/Getty Images

Both the state House and Senate have approved a bill that allows pharmacists to dispense the antiparasitic drug without a prescription while shielding them “from any liability that could arise from dispensing ivermectin,” Nashville Public Radio reported.

The drug’s manufacturer, Merck, said over a year ago that there is “no scientific basis for a potential therapeutic effect against COVID-19 from preclinical studies … and a concerning lack of safety data.” More recently, a study published in the New England Journal of Medicine showed that ivermectin treatment had no important benefits in patients with COVID.

Last week, the bill’s Senate sponsor, Frank Niceley of Strawberry Plains, said that it was all about safety, as he explained to NPR station WPLN: “It’s a lot safer to go to your pharmacist and let him tell you how much ivermectin to take than it is to go to the co-op and guess what size horse you are.”

And on that note, here are a few more items of business that just might end up on the legislature’s calendar:

• Horses will be allowed to “share” their unused ivermectin with humans and other mammals.
• An apple a day not only keeps the doctor away, but the IRS and the FDA as well.
• Colon cleansing is more fun than humans should be allowed to have.
• TikTok videos qualify as CME.

Who needs medical degrees anyway?

It’s no secret that doctors make a fair chunk of change. It’s a lucrative profession, but that big fat paycheck is siloed behind long, tough years of medical school and residency. It’s not an easy path doctors walk. Or at least, it’s not supposed to be. Anything’s easy if you’re willing to lie.

vchal/Thinkstock

That brings us to Sonia, a 31-year-old woman from northern France with a bachelor’s degree in real estate management who wasn’t bringing in enough money for her three children, at least not to her satisfaction. Naturally, the only decision was to forge some diplomas from the University of Strasbourg, as well as a certificate from the French Order of Physicians. Sonia got hired as a general practitioner by using the identities of two doctors who shared her name. She had no experience, had no idea what she was doing, and was wearing a GPS tagging bracelet for an unrelated crime, so she was quickly caught and exposed in October 2021, after, um, 3 years of fake doctoring, according to France Live.

Not to be deterred by this temporary setback, Sonia proceeded to immediately find work as an ophthalmologist, a career that requires more than 10 years of training, continuing her fraudulent medical career until recently, when she was caught again and sentenced to 3 years in prison. She did make 70,000 euros a year as a fake doctor, which isn’t exactly huge money, but certainly not bad either.

We certainly hope she’s learned her lesson about impersonating a doctor, at this point, but maybe she should just go to medical school. If not, northern France might just end up with a new endocrinologist or oncologist floating around in 3 years.
 

Speak louder, I can’t see you

With the introduction of FaceTime and the pandemic pushing work and social events to Zoom, video calls have become ubiquitous. Along the way, however, we’ve had to learn to adjust to technical difficulties. Often by yelling at the screen when the video quality is disrupted. Waving our hands and arms, speaking louder. Sound like you?

Tumisu/Pixabay

Well, a new study published in Royal Society Open Science shows that it sounds like a lot of us.

James Trujillo of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who was lead author of the paper, said on Eurekalert that “previous research has shown that speech and gestures are linked, but ours is the first to look into how visuals impact our behavior in those fields.”

He and his associates set up 40 participants in separate rooms to have conversations in pairs over a video chat. Over the course of 40 minutes, the video quality started to deteriorate from clear to extremely blurry. When the video quality was affected, participants started with gestures but as the quality continued to lessen the gestures increased and so did the decibels of their voices.

Even when the participants could barely see each other, they still gestured and their voices were even louder, positively supporting the idea that gestures and speech are a dynamically linked when it comes to communication. Even on regular phone calls, when we can’t see each other at all, people make small movements and gestures, Mr. Trujillo said.

So, the next time the Wifi is terrible and your video calls keep cutting out, don’t worry about looking foolish screaming at the computer. We’ve all been there.
 

Seek a doctor if standing at attention for more than 4 hours

Imbrochável. In Brazil, it means “unfloppable” or “flaccid proof.” It’s also a word that Brazilian president Jair Bolsonaro likes to use when referring to himself. Gives you a good idea of what he’s all about. Imagine his embarrassment when news recently broke about more than 30,000 pills of Viagra that had been secretly distributed to the Brazilian military.

PublicDomainPictures/Pixabay

The military offered a simple and plausible explanation: The Viagra had been prescribed to treat pulmonary hypertension. Fair, but when a Brazilian newspaper dug a little deeper, they found that this was not the case. The Viagra was, in general, being used for its, shall we say, traditional purpose.

Many Brazilians reacted poorly to the news that their tax dollars were being used to provide Brazilian soldiers with downstairs assistance, with the standard associated furor on social media. A rival politician, Ciro Gomes, who is planning on challenging the president in an upcoming election, had perhaps the best remark on the situation: “Unless they’re able to prove they’re developing some kind of secret weapon – capable of revolutionizing the international arms industry – it’ll be tough to justify the purchase of 35,000 units of a erectile dysfunction drug.”

Hmm, secret weapon. Well, a certain Russian fellow has made a bit of a thrust into world affairs recently. Does anyone know if Putin is sitting on a big Viagra stash?
 

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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

A long-acting subcutaneous antipsychotic (LASCA) suspension that combines risperidone with a novel copolymer substantially reduces risk for relapse and prolongs time to impending relapse for patients with schizophrenia, new research suggests.

In the phase 3 Risperidone Subcutaneous Extended-Release (RISE) trial, which included more than 500 patients with schizophrenia, those who received the novel combination treatment, known as TV-46000, had relapse reduced by 80% with monthly administration and by 63.5% with the bimonthly dose.

“Long-acting injectable medications are grossly underutilized,” study investigator John M. Kane, MD, Hofstra University, Hempstead, N.Y., told this news organization.

The attributes of TV-46000, which include its subcutaneous delivery rather than intramuscular injections, its being active within 24 hours of first treatment, and its being administered monthly or bimonthly, “might be advantageous for some patients,” Dr. Kane noted.

Because it is also effective in reducing risk for relapse, TV-46000 is “another alternative when people are looking at the possibility of using a long-acting injectable formulation,” he added.

The findings were presented at the annual congress of the Schizophrenia International Research Society.
 

Time to relapse

To examine the efficacy and safety of monthly and bimonthly doses of the drug, the researchers recruited patients aged 13-65 years who were diagnosed with schizophrenia more than a year previously and who had experienced at least one relapse in the previous 24 months.

After a screening period of up to 4 weeks, participants entered a 12-week pretreatment phase, during which their condition was stabilized on oral risperidone. During this period, the patients’ conditions had to remain stable for at least 4 consecutive weeks.

Patients were then randomly assigned in a 1:1:1 ratio to receive TV-46000 monthly, TV-46000 every 2 months, or matching placebo. All doses were given as subcutaneous injections.

Treatment was continued until participants experienced a relapse event, met at least one criteria for study withdrawal, or the study recorded a total of 90 or more relapse events.

Of 1,267 patients screened, 863 were enrolled in the study, and 544 underwent randomization. The median age of the patients who underwent randomization was 52 years; 61% were male; and the majority (59%) were Black.

In addition, the average length of time with the disease was 20.8 years, and the average time since the most recent relapse was 10.2 months.

The primary endpoint was time to impending relapse, the criteria for which included the following:

• Increases in Positive and Negative Syndrome Scale (PANSS) scores from randomization.
• Hospitalization because of worsening psychotic symptoms.
• Violent behavior resulting in clinically significant injury or damage.

Well tolerated?

In the intent-to-treat population, which comprised all adults who underwent randomization, monthly TV-46000 was associated with a fivefold prolongation of time to impending relapse in comparison with placebo; TV-46000 given every 2 months prolonged the time 2.7-fold.

This translated into a significant benefit vs. placebo for both TV-46000 monthly (hazard ratio for impending relapse, 0.2) and TV-46000 every 2 months (HR, 0.375; P < .0001 for both comparisons).

At the trial’s endpoint, impending relapse rates were 29% in the placebo group vs. 7% in the TV-46000 monthly group and 13% in the group that received TV-46000 every 2 months (P < .0001 for both).

While more patients in the two active-treatment groups met the strict criteria for remission, which included no relapse during the study and PANSS scores of 3 or less for at least 6 months prior to the study endpoint, the differences were not significant.

Treatment-related adverse events (AEs) were experienced by 39%-42% of the TV-46000 groups and by 26% of the placebo group. Serious AEs were experienced by 4%-6% of the TV-46000 groups and by 8% of the placebo group.

The investigators note that TV-46000 was “well tolerated” and that there were no new safety signals in comparison with what is already known about risperidone and “other long-acting risperidone formulations.”

Expanding on the reasons why long-acting antipsychotics are underprescribed, Dr. Kane said that “doctors often overestimate how adherent their patients are.”

He added that doctors may worry they are “insulting” their patient by suggesting they receive injections in order to increase adherence and that doctors are “not very good” at having these types of conversation with their patients.

“We did a study where we trained the clinical staff on how to have those conversations, and the result was the uptake [in patients switching to long-acting antipsychotics] was very high,” Dr. Kane said.

The personnel who received training included all of the medical team, therapists, who spend “much more time” with the patient than does the prescriber, and also social workers, case managers, and rehabilitation counselors, who are typically “not very familiar” with the idea of long-acting medications, he added.
 

‘Highly desirable’ option

Commenting on the study, Stephen R. Saklad, PharmD, director of the psychiatric pharmacy program, University of Texas Health Science Center at San Antonio, said that to call TV-46000 a LASCA rather than a depot injection is merely a “change in nomenclature.”

However, compared with a once-monthly subcutaneous injection of risperidone (Perseris), which was approved by the U.S. Food and Drug Administration in 2018 for the treatment of schizophrenia, the new drug has fewer injection site reactions, said Dr. Saklad, who was not involved with the current research.

That benefit plus having efficacy similar to that of oral risperidone and having the “more patient- and clinician-desirable administration location” of the upper arm as well as the abdomen means the option to switch a risperidone-stabilized patient directly to TV-46000 monthly or bimonthly is “highly desirable,” he added.

Dr. Saklad also noted the reduction in the likelihood of impending relapse with TV-46000 over placebo is a relatively large effect size “and shows the value toward improving the care of these patients.”

In addition, he agreed with Dr. Kane that the uptake of long-acting antipsychotics is “deplorably low.”

“This is due to a number of factors that include patient reluctance to get a ‘shot’ or ‘jab,’ clinician inexperience with LAIs during training, and the incorrect presentation of LAIs as a punishment paradigm for ‘bad’ patients,” Dr. Saklad said.

He added that “everyone tires of taking their medication or just forgets to take a dose,” and most patients with other disorders will resume their medication the next day.

However, patients with schizophrenia have a “specific cognitive difficulty” in making the connection between stopping their medication and a later relapse. If they miss a dose, they will “incorrectly conclude that they are now ‘well’ and don’t need the medication any longer,” he said.

Dr. Saklad stressed that for a patient with schizophrenia a relapse can mean substantial loss of function and of assets such as housing or support networks, and many “will complete suicide.”

The study was supported by Teva Branded Pharmaceutical Products R&D. Dr. Kane reported relationships with Alkermes, Allergan, Dainioppon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen, Janssen Pharmaceuticals, Johnson & Johnson, LB Pharmaceuticals, Merck, Neurocine, North Shore Therapeutics, Novartis Pharmaceutical, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva, Otsuka, Lundbeck, Sunovion, UptoDate, and Vanguard Research Group.

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