ALL

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Survival from pediatric acute lymphoblastic leukemia (ALL) in a Mexican hospital improved significantly through a close cross-border collaboration with a nearby U.S. center that provided training and improved access.

A team from a hospital in San Diego combined a previously established training program from the World Health Organization with a new collaboration, which resulted in improvements in care standards and sustainability of care in a center in Tijuana, Mexico, just 23 miles away.

Implementation of the program in 2013 led to a significant 6% improvement in 5-year overall survival for children with ALL.

For patients at standard risk, 5-year overall survival increased from 73% to 100% after implementation of the program.

“This is really remarkable because this survival is the same as we have here in San Diego,” commented Paula Aristizabal, MD, MAS, a pediatric hematologist/oncologist at Rady Children’s Hospital, San Diego, at a press briefing before the annual meeting of the American Society of Clinical Oncology.

The findings show that “sustained improvements in cancer outcomes in low- and middle-income countries [LMICs] are feasible with innovative cross-border programs, particularly in borders that are shared” between a high- and low-income country, she commented. In other words, “it takes a village in both countries” to drive up standards.

Dr. Aristizabal also noted that the partnership will continue with a particularly focus on improving survival among patients with high-risk disease.

“We like to call it ‘twinning,’ because that means we are twins forever,” she said. “This is not a marriage that can be dissolved.”
 

‘Huge survival gap’

“The burden of childhood cancer has increased globally, but unfortunately, survival in low- and middle-income countries has not improved at the same level as in high-income countries,” Dr. Aristizabal commented.

This has resulted in a “huge survival gap” between high-income countries and the LMICs. ALL is now a leading cause of death among children in these countries, she commented.

“This study illustrates collaborative strategies that can be put into place today that could greatly improve outcomes for children with cancer globally,” commented Julie R. Gralow, MD, ASCO chief medical officer and executive vice president.

Speaking at the press conference, she added: “As I’ve heard Princess Dina Mired of Jordan say many times: ‘Your ZIP code should not determine if you survive cancer.’ ”

She said the differences in ALL survival between the United States and Mexico are an “example of children being so close in terms of proximity not having the same advantages.”

Also commenting, ASCO President Eric Winer, MD, from the Yale Cancer Center, New Haven, Conn., asked whether the proximity of the hospitals in San Diego and Tijuana “makes a difference, or do you think this is something that done ... at a distance?”

Dr. Aristizabal said that the proximity between the institutions “has been extremely helpful,” as they can go between hospitals in just 30 minutes.

However, “one of the things that we learned with COVID is that we can do a lot of things remotely,” she answered.

“Some of the projects that we started in Tijuana, through our collaboration with St. Jude Children’s Research Hospital, we have been able to implement in many other centers in Mexico,” she said.
 

Study details

Rady Children’s Hospital partnered with the public sector in Baja California, with the aim of improving outcomes in children’s cancer, she explained.

In 2008, the team collaborated with St. Jude Children’s Research Hospital, Memphis, to establish a training program in the Hospital General Tijuana in Tijuana that shared knowledge, technology, and organizational skills.

The team also consulted on clinical cases and set up education and research programs, all with the aim of building capacity and sustainability in Mexico.

“As the number of leukemia patients increased, we wanted to decrease depending on their international collaborators in the U.S. and ensure long-term sustainability,” Dr. Aristizabal explained.

This led in 2013 to the implementation of the WHO Framework for Action HSS training model, which has several components, including health service delivery.

Combined with the previously established model, the overall goals of the program were to improve health outcomes, systems efficiency, timely access to care, and social and financial risk protection.

Dr. Aristizabal said in an interview that this involved developing highly specific leukemia treatment guidelines, which have now gone through three iterations, as well as guidelines for supportive care.

Working with a local foundation, the team has also “focused on providing psychosocial support, nutritional support, a shelter for families that live 12-14 hours away from the pediatric cancer center, as well as food subsidies, trying to address financial toxicity and food insecurity in these families.”
 

Impact of the collaboration

To assess the impact of the WHO framework, the researchers conducted a study that involved 109 children with ALL who were treated at Hospital General Tijuana over the preimplementation phase in 2008-2012 and the postimplementation phase in 2013-2017.

The mean age of the patients was 7.04 years, and 50.4% were girls. The majority (67%) were classified as having high-risk disease.

Over the entire study period, the 5-year overall survival rate was 65%. Analysis revealed that between the pre- and postimplementation periods, 5-year overall survival increased from 59% to 65%, which Dr. Aristizabal described as “a significant improvement.”

Among high-risk patients, the improvement in 5-year survival between the pre- and postimplementation period went from 48% to 55%.

“This is an area for improvement,” Dr. Aristizabal said, “and we’re working on additional strategies to help improve survival for high-risk patients.

The study was funded by Rady Children’s Hospital, the Mexican Secretary of Health, and the Patronato Foundation. Dr. Aristizabal and coauthors reported no relevant financial relationships. Dr. Gralow reported relationships with Genentech and Roche. Dr. Winer reported relationships with Leap Therapeutics, Jounce Therapeutics, Carrick Therapeutics, and Genentech.

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

Survival from pediatric acute lymphoblastic leukemia (ALL) in a Mexican hospital improved significantly through a close cross-border collaboration with a nearby U.S. center that provided training and improved access.

A team from a hospital in San Diego combined a previously established training program from the World Health Organization with a new collaboration, which resulted in improvements in care standards and sustainability of care in a center in Tijuana, Mexico, just 23 miles away.

Implementation of the program in 2013 led to a significant 6% improvement in 5-year overall survival for children with ALL.

For patients at standard risk, 5-year overall survival increased from 73% to 100% after implementation of the program.

“This is really remarkable because this survival is the same as we have here in San Diego,” commented Paula Aristizabal, MD, MAS, a pediatric hematologist/oncologist at Rady Children’s Hospital, San Diego, at a press briefing before the annual meeting of the American Society of Clinical Oncology.

The findings show that “sustained improvements in cancer outcomes in low- and middle-income countries [LMICs] are feasible with innovative cross-border programs, particularly in borders that are shared” between a high- and low-income country, she commented. In other words, “it takes a village in both countries” to drive up standards.

Dr. Aristizabal also noted that the partnership will continue with a particularly focus on improving survival among patients with high-risk disease.

“We like to call it ‘twinning,’ because that means we are twins forever,” she said. “This is not a marriage that can be dissolved.”
 

‘Huge survival gap’

“The burden of childhood cancer has increased globally, but unfortunately, survival in low- and middle-income countries has not improved at the same level as in high-income countries,” Dr. Aristizabal commented.

This has resulted in a “huge survival gap” between high-income countries and the LMICs. ALL is now a leading cause of death among children in these countries, she commented.

“This study illustrates collaborative strategies that can be put into place today that could greatly improve outcomes for children with cancer globally,” commented Julie R. Gralow, MD, ASCO chief medical officer and executive vice president.

Speaking at the press conference, she added: “As I’ve heard Princess Dina Mired of Jordan say many times: ‘Your ZIP code should not determine if you survive cancer.’ ”

She said the differences in ALL survival between the United States and Mexico are an “example of children being so close in terms of proximity not having the same advantages.”

Also commenting, ASCO President Eric Winer, MD, from the Yale Cancer Center, New Haven, Conn., asked whether the proximity of the hospitals in San Diego and Tijuana “makes a difference, or do you think this is something that done ... at a distance?”

Dr. Aristizabal said that the proximity between the institutions “has been extremely helpful,” as they can go between hospitals in just 30 minutes.

However, “one of the things that we learned with COVID is that we can do a lot of things remotely,” she answered.

“Some of the projects that we started in Tijuana, through our collaboration with St. Jude Children’s Research Hospital, we have been able to implement in many other centers in Mexico,” she said.
 

Study details

Rady Children’s Hospital partnered with the public sector in Baja California, with the aim of improving outcomes in children’s cancer, she explained.

In 2008, the team collaborated with St. Jude Children’s Research Hospital, Memphis, to establish a training program in the Hospital General Tijuana in Tijuana that shared knowledge, technology, and organizational skills.

The team also consulted on clinical cases and set up education and research programs, all with the aim of building capacity and sustainability in Mexico.

“As the number of leukemia patients increased, we wanted to decrease depending on their international collaborators in the U.S. and ensure long-term sustainability,” Dr. Aristizabal explained.

This led in 2013 to the implementation of the WHO Framework for Action HSS training model, which has several components, including health service delivery.

Combined with the previously established model, the overall goals of the program were to improve health outcomes, systems efficiency, timely access to care, and social and financial risk protection.

Dr. Aristizabal said in an interview that this involved developing highly specific leukemia treatment guidelines, which have now gone through three iterations, as well as guidelines for supportive care.

Working with a local foundation, the team has also “focused on providing psychosocial support, nutritional support, a shelter for families that live 12-14 hours away from the pediatric cancer center, as well as food subsidies, trying to address financial toxicity and food insecurity in these families.”
 

Impact of the collaboration

To assess the impact of the WHO framework, the researchers conducted a study that involved 109 children with ALL who were treated at Hospital General Tijuana over the preimplementation phase in 2008-2012 and the postimplementation phase in 2013-2017.

The mean age of the patients was 7.04 years, and 50.4% were girls. The majority (67%) were classified as having high-risk disease.

Over the entire study period, the 5-year overall survival rate was 65%. Analysis revealed that between the pre- and postimplementation periods, 5-year overall survival increased from 59% to 65%, which Dr. Aristizabal described as “a significant improvement.”

Among high-risk patients, the improvement in 5-year survival between the pre- and postimplementation period went from 48% to 55%.

“This is an area for improvement,” Dr. Aristizabal said, “and we’re working on additional strategies to help improve survival for high-risk patients.

The study was funded by Rady Children’s Hospital, the Mexican Secretary of Health, and the Patronato Foundation. Dr. Aristizabal and coauthors reported no relevant financial relationships. Dr. Gralow reported relationships with Genentech and Roche. Dr. Winer reported relationships with Leap Therapeutics, Jounce Therapeutics, Carrick Therapeutics, and Genentech.

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

Survival from pediatric acute lymphoblastic leukemia (ALL) in a Mexican hospital improved significantly through a close cross-border collaboration with a nearby U.S. center that provided training and improved access.

A team from a hospital in San Diego combined a previously established training program from the World Health Organization with a new collaboration, which resulted in improvements in care standards and sustainability of care in a center in Tijuana, Mexico, just 23 miles away.

Implementation of the program in 2013 led to a significant 6% improvement in 5-year overall survival for children with ALL.

For patients at standard risk, 5-year overall survival increased from 73% to 100% after implementation of the program.

“This is really remarkable because this survival is the same as we have here in San Diego,” commented Paula Aristizabal, MD, MAS, a pediatric hematologist/oncologist at Rady Children’s Hospital, San Diego, at a press briefing before the annual meeting of the American Society of Clinical Oncology.

The findings show that “sustained improvements in cancer outcomes in low- and middle-income countries [LMICs] are feasible with innovative cross-border programs, particularly in borders that are shared” between a high- and low-income country, she commented. In other words, “it takes a village in both countries” to drive up standards.

Dr. Aristizabal also noted that the partnership will continue with a particularly focus on improving survival among patients with high-risk disease.

“We like to call it ‘twinning,’ because that means we are twins forever,” she said. “This is not a marriage that can be dissolved.”
 

‘Huge survival gap’

“The burden of childhood cancer has increased globally, but unfortunately, survival in low- and middle-income countries has not improved at the same level as in high-income countries,” Dr. Aristizabal commented.

This has resulted in a “huge survival gap” between high-income countries and the LMICs. ALL is now a leading cause of death among children in these countries, she commented.

“This study illustrates collaborative strategies that can be put into place today that could greatly improve outcomes for children with cancer globally,” commented Julie R. Gralow, MD, ASCO chief medical officer and executive vice president.

Speaking at the press conference, she added: “As I’ve heard Princess Dina Mired of Jordan say many times: ‘Your ZIP code should not determine if you survive cancer.’ ”

She said the differences in ALL survival between the United States and Mexico are an “example of children being so close in terms of proximity not having the same advantages.”

Also commenting, ASCO President Eric Winer, MD, from the Yale Cancer Center, New Haven, Conn., asked whether the proximity of the hospitals in San Diego and Tijuana “makes a difference, or do you think this is something that done ... at a distance?”

Dr. Aristizabal said that the proximity between the institutions “has been extremely helpful,” as they can go between hospitals in just 30 minutes.

However, “one of the things that we learned with COVID is that we can do a lot of things remotely,” she answered.

“Some of the projects that we started in Tijuana, through our collaboration with St. Jude Children’s Research Hospital, we have been able to implement in many other centers in Mexico,” she said.
 

Study details

Rady Children’s Hospital partnered with the public sector in Baja California, with the aim of improving outcomes in children’s cancer, she explained.

In 2008, the team collaborated with St. Jude Children’s Research Hospital, Memphis, to establish a training program in the Hospital General Tijuana in Tijuana that shared knowledge, technology, and organizational skills.

The team also consulted on clinical cases and set up education and research programs, all with the aim of building capacity and sustainability in Mexico.

“As the number of leukemia patients increased, we wanted to decrease depending on their international collaborators in the U.S. and ensure long-term sustainability,” Dr. Aristizabal explained.

This led in 2013 to the implementation of the WHO Framework for Action HSS training model, which has several components, including health service delivery.

Combined with the previously established model, the overall goals of the program were to improve health outcomes, systems efficiency, timely access to care, and social and financial risk protection.

Dr. Aristizabal said in an interview that this involved developing highly specific leukemia treatment guidelines, which have now gone through three iterations, as well as guidelines for supportive care.

Working with a local foundation, the team has also “focused on providing psychosocial support, nutritional support, a shelter for families that live 12-14 hours away from the pediatric cancer center, as well as food subsidies, trying to address financial toxicity and food insecurity in these families.”
 

Impact of the collaboration

To assess the impact of the WHO framework, the researchers conducted a study that involved 109 children with ALL who were treated at Hospital General Tijuana over the preimplementation phase in 2008-2012 and the postimplementation phase in 2013-2017.

The mean age of the patients was 7.04 years, and 50.4% were girls. The majority (67%) were classified as having high-risk disease.

Over the entire study period, the 5-year overall survival rate was 65%. Analysis revealed that between the pre- and postimplementation periods, 5-year overall survival increased from 59% to 65%, which Dr. Aristizabal described as “a significant improvement.”

Among high-risk patients, the improvement in 5-year survival between the pre- and postimplementation period went from 48% to 55%.

“This is an area for improvement,” Dr. Aristizabal said, “and we’re working on additional strategies to help improve survival for high-risk patients.

The study was funded by Rady Children’s Hospital, the Mexican Secretary of Health, and the Patronato Foundation. Dr. Aristizabal and coauthors reported no relevant financial relationships. Dr. Gralow reported relationships with Genentech and Roche. Dr. Winer reported relationships with Leap Therapeutics, Jounce Therapeutics, Carrick Therapeutics, and Genentech.

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

Hagop Kantarjian, MD, has been named the recipient of the 2023 David A. Karnofsky Memorial Award by the American Society of Clinical Oncology in recognition of his practice-changing clinical-translational research in leukemia.

This award is the society’s “highest scientific honor, and I am extremely happy and honored to receive it,” Dr. Kantarjian commented in an interview with this news organization.

Dr. Kantarjian serves as the chair of the department of leukemia and currently holds the Samsung Distinguished University Chair in Cancer Medicine at the University of Texas MD Anderson Cancer Center, Houston.

“No doubt that this is not an individual award. It represents an award for the accomplishments of all the leukemia faculty at MD Anderson across 4 decades. It’s really a teamwork effort that led to so many discoveries and improvements in treatment and care of patients with leukemia,” he commented.

The David A. Karnofsky Memorial Award has been presented annually since 1970 to recognize oncologists who have made outstanding contributions to cancer research, diagnosis, or treatment, ASCO noted.
 

From Lebanon to Texas

Dr. Kantarjian received his medical degree from the American University of Beirut, in Lebanon, in 1979 and completed his residency in internal medicine at the same institution in 1981.

It was his experience at MD Anderson as a young medical student and later as a fellow that fueled his interest and career in leukemia, he said.

“In 1978, I took a 4-month elective at MD Anderson, and I soon realized how different and innovative the atmosphere at MD Anderson was, compared to where I was training in Lebanon,” Dr. Kantarjian told this news organization.

Working with mentors that included MD Anderson heavyweights Emil Freireich, MD, Kenneth McCredie, MD, and Michael Keating, MD, helped shape his career and guide his leukemia research, he said.
 

Transformative impact on leukemia outcomes

The award citation notes that over the past 4 decades, Dr. Kantarjian’s research has transformed some standards of care and has dramatically improved survival in several leukemia subtypes, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute lymphocytic leukemia (ALL).

“Four decades ago, most of the leukemias were incurable. Today, most of the leukemias are potentially curable with targeted therapies. That’s what I am most proud of,” Dr. Kantarjian told this news organization.

Among Dr. Kantarjian’s contributions to the field of leukemia:

• Developing the HYPER-CVAD regimen (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) as a standard-of-care, frontline therapy for adults with ALL.
• Establishing clinical biology parameters of CML, including definitions of CML phases and cytogenetic responses, and establishing new prognostic factors that were subsequently adopted in studies of tyrosine kinase inhibitors.
• Leading the development of decitabine and epigenetic hypomethylation therapy for MDS and for older/unfit patients with AML.
• Pioneering research with hypomethylating agents (HMAs) in combination with venetoclax, which led to FDA approval of HMA-venetoclax combinations for older/unfit patients with AML.
• Championing the development of clofarabine, conducting animal toxicology studies, and leading subsequent phase 1 and 2 trials and pivotal phase 3 and 4 trials that led to FDA approval of clofarabine for pediatric ALL.
• Developing several FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and venetoclax, which all received FDA approval for the treatment of AML and its subsets.
• Developing regimens for inotuzumab and blinatumomab combined with chemotherapy for adults with pre-B ALL.
• Working on the development of imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and omacetaxine, which all received FDA approval for CML therapy.

“Dr. Kantarjian’s long list of accomplishments and groundbreaking discoveries are a testament to his lifelong commitment to impactful cancer research and patient care,” Giulio Draetta, MD, PhD, chief scientific officer at MD Anderson, said in a statement.
 

Giving back

Dr. Kantarjian has written more than 2,200 peer-reviewed articles and more than 100 book chapters. In 2012, he cofounded the Society of Hematologic Oncology, which has now expanded worldwide.

He has served on multiple ASCO committees throughout the years and served on the ASCO board of directors from 2010 to 2015.

Dr. Kantarjian is passionately involved in mentoring and education. In 2000 he created the MD Anderson Leukemia Fellowship, which now trains about 10 fellows in leukemia annually.

He is a nonresident fellow in health care at the Rice Baker Institute and has written extensively on important health care issues in cancer, including the importance of universal equitable health care, health care safety nets, health care as a human right, and the problem of drug shortages.

Dr. Kantarjian is a strong advocate for more affordable drug therapies. For years he has been outspoken about the high price of leukemia drugs and has written high-profile articles in medical journals. He has even appeared on a popular television program to publicize the issue.

“Drug costs have been increasing over time. If you think about it, even if you discover a drug that cures cancer, but the drug is affordable for the 1% of the patients, then you have no cure for cancer,” Dr. Kantarjian told this news organization.

“I started speaking about the issue of the cancer drug costs in 2012. Unfortunately, we have not made progress simply because of the for-profit nature of health care and the strong lobbying by drug companies,” he added. Dr. Kantarjian hopes new legislation will eventually turn the tide.

Dr. Kantarjian has received many other honors throughout his distinguished career, including the American Lebanese Medical Association’s Lifetime Achievement Award, the American Association for Cancer Research’s Joseph H. Burchenal Memorial Award, and the Leukemia Society of America’s Outstanding Service to Mankind Award. He also was named an ASCO Fellow and a Leukemia Society of America Special Fellow and Scholar.

Dr. Kantarjian will be presented with the 2023 David A. Karnofsky Memorial Award, which includes a $25,000 honorarium, and will give a scientific lecture about his research at the ASCO annual meeting in Chicago in early June.

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

Hagop Kantarjian, MD, has been named the recipient of the 2023 David A. Karnofsky Memorial Award by the American Society of Clinical Oncology in recognition of his practice-changing clinical-translational research in leukemia.

This award is the society’s “highest scientific honor, and I am extremely happy and honored to receive it,” Dr. Kantarjian commented in an interview with this news organization.

Dr. Kantarjian serves as the chair of the department of leukemia and currently holds the Samsung Distinguished University Chair in Cancer Medicine at the University of Texas MD Anderson Cancer Center, Houston.

“No doubt that this is not an individual award. It represents an award for the accomplishments of all the leukemia faculty at MD Anderson across 4 decades. It’s really a teamwork effort that led to so many discoveries and improvements in treatment and care of patients with leukemia,” he commented.

The David A. Karnofsky Memorial Award has been presented annually since 1970 to recognize oncologists who have made outstanding contributions to cancer research, diagnosis, or treatment, ASCO noted.
 

From Lebanon to Texas

Dr. Kantarjian received his medical degree from the American University of Beirut, in Lebanon, in 1979 and completed his residency in internal medicine at the same institution in 1981.

It was his experience at MD Anderson as a young medical student and later as a fellow that fueled his interest and career in leukemia, he said.

“In 1978, I took a 4-month elective at MD Anderson, and I soon realized how different and innovative the atmosphere at MD Anderson was, compared to where I was training in Lebanon,” Dr. Kantarjian told this news organization.

Working with mentors that included MD Anderson heavyweights Emil Freireich, MD, Kenneth McCredie, MD, and Michael Keating, MD, helped shape his career and guide his leukemia research, he said.
 

Transformative impact on leukemia outcomes

The award citation notes that over the past 4 decades, Dr. Kantarjian’s research has transformed some standards of care and has dramatically improved survival in several leukemia subtypes, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute lymphocytic leukemia (ALL).

“Four decades ago, most of the leukemias were incurable. Today, most of the leukemias are potentially curable with targeted therapies. That’s what I am most proud of,” Dr. Kantarjian told this news organization.

Among Dr. Kantarjian’s contributions to the field of leukemia:

• Developing the HYPER-CVAD regimen (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) as a standard-of-care, frontline therapy for adults with ALL.
• Establishing clinical biology parameters of CML, including definitions of CML phases and cytogenetic responses, and establishing new prognostic factors that were subsequently adopted in studies of tyrosine kinase inhibitors.
• Leading the development of decitabine and epigenetic hypomethylation therapy for MDS and for older/unfit patients with AML.
• Pioneering research with hypomethylating agents (HMAs) in combination with venetoclax, which led to FDA approval of HMA-venetoclax combinations for older/unfit patients with AML.
• Championing the development of clofarabine, conducting animal toxicology studies, and leading subsequent phase 1 and 2 trials and pivotal phase 3 and 4 trials that led to FDA approval of clofarabine for pediatric ALL.
• Developing several FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and venetoclax, which all received FDA approval for the treatment of AML and its subsets.
• Developing regimens for inotuzumab and blinatumomab combined with chemotherapy for adults with pre-B ALL.
• Working on the development of imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and omacetaxine, which all received FDA approval for CML therapy.

“Dr. Kantarjian’s long list of accomplishments and groundbreaking discoveries are a testament to his lifelong commitment to impactful cancer research and patient care,” Giulio Draetta, MD, PhD, chief scientific officer at MD Anderson, said in a statement.
 

Giving back

Dr. Kantarjian has written more than 2,200 peer-reviewed articles and more than 100 book chapters. In 2012, he cofounded the Society of Hematologic Oncology, which has now expanded worldwide.

He has served on multiple ASCO committees throughout the years and served on the ASCO board of directors from 2010 to 2015.

Dr. Kantarjian is passionately involved in mentoring and education. In 2000 he created the MD Anderson Leukemia Fellowship, which now trains about 10 fellows in leukemia annually.

He is a nonresident fellow in health care at the Rice Baker Institute and has written extensively on important health care issues in cancer, including the importance of universal equitable health care, health care safety nets, health care as a human right, and the problem of drug shortages.

Dr. Kantarjian is a strong advocate for more affordable drug therapies. For years he has been outspoken about the high price of leukemia drugs and has written high-profile articles in medical journals. He has even appeared on a popular television program to publicize the issue.

“Drug costs have been increasing over time. If you think about it, even if you discover a drug that cures cancer, but the drug is affordable for the 1% of the patients, then you have no cure for cancer,” Dr. Kantarjian told this news organization.

“I started speaking about the issue of the cancer drug costs in 2012. Unfortunately, we have not made progress simply because of the for-profit nature of health care and the strong lobbying by drug companies,” he added. Dr. Kantarjian hopes new legislation will eventually turn the tide.

Dr. Kantarjian has received many other honors throughout his distinguished career, including the American Lebanese Medical Association’s Lifetime Achievement Award, the American Association for Cancer Research’s Joseph H. Burchenal Memorial Award, and the Leukemia Society of America’s Outstanding Service to Mankind Award. He also was named an ASCO Fellow and a Leukemia Society of America Special Fellow and Scholar.

Dr. Kantarjian will be presented with the 2023 David A. Karnofsky Memorial Award, which includes a $25,000 honorarium, and will give a scientific lecture about his research at the ASCO annual meeting in Chicago in early June.

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

Hagop Kantarjian, MD, has been named the recipient of the 2023 David A. Karnofsky Memorial Award by the American Society of Clinical Oncology in recognition of his practice-changing clinical-translational research in leukemia.

This award is the society’s “highest scientific honor, and I am extremely happy and honored to receive it,” Dr. Kantarjian commented in an interview with this news organization.

Dr. Kantarjian serves as the chair of the department of leukemia and currently holds the Samsung Distinguished University Chair in Cancer Medicine at the University of Texas MD Anderson Cancer Center, Houston.

“No doubt that this is not an individual award. It represents an award for the accomplishments of all the leukemia faculty at MD Anderson across 4 decades. It’s really a teamwork effort that led to so many discoveries and improvements in treatment and care of patients with leukemia,” he commented.

The David A. Karnofsky Memorial Award has been presented annually since 1970 to recognize oncologists who have made outstanding contributions to cancer research, diagnosis, or treatment, ASCO noted.
 

From Lebanon to Texas

Dr. Kantarjian received his medical degree from the American University of Beirut, in Lebanon, in 1979 and completed his residency in internal medicine at the same institution in 1981.

It was his experience at MD Anderson as a young medical student and later as a fellow that fueled his interest and career in leukemia, he said.

“In 1978, I took a 4-month elective at MD Anderson, and I soon realized how different and innovative the atmosphere at MD Anderson was, compared to where I was training in Lebanon,” Dr. Kantarjian told this news organization.

Working with mentors that included MD Anderson heavyweights Emil Freireich, MD, Kenneth McCredie, MD, and Michael Keating, MD, helped shape his career and guide his leukemia research, he said.
 

Transformative impact on leukemia outcomes

The award citation notes that over the past 4 decades, Dr. Kantarjian’s research has transformed some standards of care and has dramatically improved survival in several leukemia subtypes, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute lymphocytic leukemia (ALL).

“Four decades ago, most of the leukemias were incurable. Today, most of the leukemias are potentially curable with targeted therapies. That’s what I am most proud of,” Dr. Kantarjian told this news organization.

Among Dr. Kantarjian’s contributions to the field of leukemia:

• Developing the HYPER-CVAD regimen (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) as a standard-of-care, frontline therapy for adults with ALL.
• Establishing clinical biology parameters of CML, including definitions of CML phases and cytogenetic responses, and establishing new prognostic factors that were subsequently adopted in studies of tyrosine kinase inhibitors.
• Leading the development of decitabine and epigenetic hypomethylation therapy for MDS and for older/unfit patients with AML.
• Pioneering research with hypomethylating agents (HMAs) in combination with venetoclax, which led to FDA approval of HMA-venetoclax combinations for older/unfit patients with AML.
• Championing the development of clofarabine, conducting animal toxicology studies, and leading subsequent phase 1 and 2 trials and pivotal phase 3 and 4 trials that led to FDA approval of clofarabine for pediatric ALL.
• Developing several FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and venetoclax, which all received FDA approval for the treatment of AML and its subsets.
• Developing regimens for inotuzumab and blinatumomab combined with chemotherapy for adults with pre-B ALL.
• Working on the development of imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and omacetaxine, which all received FDA approval for CML therapy.

“Dr. Kantarjian’s long list of accomplishments and groundbreaking discoveries are a testament to his lifelong commitment to impactful cancer research and patient care,” Giulio Draetta, MD, PhD, chief scientific officer at MD Anderson, said in a statement.
 

Giving back

Dr. Kantarjian has written more than 2,200 peer-reviewed articles and more than 100 book chapters. In 2012, he cofounded the Society of Hematologic Oncology, which has now expanded worldwide.

He has served on multiple ASCO committees throughout the years and served on the ASCO board of directors from 2010 to 2015.

Dr. Kantarjian is passionately involved in mentoring and education. In 2000 he created the MD Anderson Leukemia Fellowship, which now trains about 10 fellows in leukemia annually.

He is a nonresident fellow in health care at the Rice Baker Institute and has written extensively on important health care issues in cancer, including the importance of universal equitable health care, health care safety nets, health care as a human right, and the problem of drug shortages.

Dr. Kantarjian is a strong advocate for more affordable drug therapies. For years he has been outspoken about the high price of leukemia drugs and has written high-profile articles in medical journals. He has even appeared on a popular television program to publicize the issue.

“Drug costs have been increasing over time. If you think about it, even if you discover a drug that cures cancer, but the drug is affordable for the 1% of the patients, then you have no cure for cancer,” Dr. Kantarjian told this news organization.

“I started speaking about the issue of the cancer drug costs in 2012. Unfortunately, we have not made progress simply because of the for-profit nature of health care and the strong lobbying by drug companies,” he added. Dr. Kantarjian hopes new legislation will eventually turn the tide.

Dr. Kantarjian has received many other honors throughout his distinguished career, including the American Lebanese Medical Association’s Lifetime Achievement Award, the American Association for Cancer Research’s Joseph H. Burchenal Memorial Award, and the Leukemia Society of America’s Outstanding Service to Mankind Award. He also was named an ASCO Fellow and a Leukemia Society of America Special Fellow and Scholar.

Dr. Kantarjian will be presented with the 2023 David A. Karnofsky Memorial Award, which includes a $25,000 honorarium, and will give a scientific lecture about his research at the ASCO annual meeting in Chicago in early June.

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

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

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

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

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

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

Patients surveyed on function

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

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

Not just a result of living longer

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

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

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

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

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

Quality of life beyond survivorship

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

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

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

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

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

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

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

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

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

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

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

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

Patients surveyed on function

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

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

Not just a result of living longer

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

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

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

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

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

Quality of life beyond survivorship

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

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

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

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

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

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

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

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

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

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

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

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

Patients surveyed on function

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

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

Not just a result of living longer

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

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

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

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

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

Quality of life beyond survivorship

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

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

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

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

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

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

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

The effects of maribavir (Levtencity) for the treatment of resistant or refractory post-transplant cytomegalovirus (CMV) infection persisted at 52-week follow-up in hematopoietic stem cell and solid organ transplant patients from the pivotal phase 3 SOLSTICE trial.

Overall mortality in the 109 patients from these subcohorts from SOLSTICE was lower, compared with mortality reported for similar populations treated with conventional therapies used to treat relapsed or refractory (R/R) CMV, according to findings presented in April at the annual meeting of the European Society for Bone and Marrow Transplantation.

“These results, in addition to the superior efficacy in CMV clearance observed for maribavir in SOLSTICE provide supportive evidence of the potential for the long-term benefit of maribavir treatment for post-transplant CMV infection,” Ishan Hirji, of Takeda Development Center Americas, and colleagues reported during a poster session at the meeting.

A retrospective chart review of the 41 hematopoietic stem cell transplant (HSCT) patients and 68 solid organ transplant (SOT) patients randomized to receive maribavir showed an overall mortality rate of 15.6% at 52 weeks after initiation of treatment with the antiviral agent. Among the HSCT patients, 14 deaths occurred (34.1%), with 8 occurring during the study periods and 6 occurring during follow-up. Among the SOT patients, three deaths occurred (4.4%), all during follow-up chart review.

Causes of death included underlying disease relapse in four patients, infection other than CMV in six patients, and one case each of CMV-related factors, transplant-related factors, acute lymphoblastic leukemia, and septic shock. Causes of death in the SOT patients included one case each of CMV-related factors, anemia, and renal failure.

“No patients had new graft loss or retransplantation during the chart review period,” the investigators noted.

The findings are notable as CMV infection occurs in 30%-70% of HSCT recipients and 16%-56% of SOT recipients and can lead to complications, including transplant failure and death. Reported 1-year mortality rates following standard therapies for CMV range from 31% to 50%, they explained.

Patients in the SOLSTICE trial received 8 weeks of treatment and were followed for 12 additional weeks. CMV clearance at the end of treatment was 55.7% in the maribavir treatment arm versus 23.9% in a control group of patients treated with investigator choice of therapy. As reported by this news organization, the findings formed the basis for U.S. Food and Drug Administration approval of maribavir in November 2021.

The current analysis included a chart review period that started 1 day after the SOLSTICE trial period and continued for 32 additional weeks.

These long-term follow-up data confirm the benefits of maribavir for the treatment of post-transplant CMV, according to the investigators, and findings from a separate study reported at the ESBMT meeting underscore the importance of the durable benefits observed with maribavir treatment.

For that retrospective study, Maria Laura Fox, of Vall d’Hebron Institute of Oncology, Barcelona, and colleagues pooled de-identified data from 250 adult HSCT recipients with R/R CMV who were treated with agents other than maribavir at transplant centers in the United States or Europe. They aimed to “generate real-world evidence on the burden of CMV infection/disease in HSCT recipients who had refractory/resistant CMV or were intolerant to current treatments.”

Nearly 92% of patients received two or more therapies to treat CMV, and 92.2% discontinued treatment or had one or more therapy dose changes or discontinuation, and 42 patients failed to achieve clearance of the CMV index episode.

CMV recurred in 35.2% of patients, and graft failure occurred in 4% of patients, the investigators reported.

All-cause mortality was 56.0%, and mortality at 1 year after identification of R/R disease or treatment intolerance was 45.2%, they noted, adding that the study results “highlight the real-world complexities and high burden of CMV infection for HSCT recipients.”

“With available anti-CMV agents [excluding maribavir], a notable proportion of patients failed to achieve viremia clearance once developing RRI [resistant, refractory, or intolerant] CMV and/or experienced recurrence, and were at risk of adverse outcomes, including myelosuppression and mortality. There is a need for therapies that achieve and maintain CMV clearance with improved safety profiles,” they concluded.

Both studies were funded by Takeda Development Center Americas, the maker of Levtencity. Ms. Hirji is an employee of Takeda and reported stock ownership. Ms. Fox reported relationships with Sierra Oncology, GlaxoSmithKline, Bristol Myers Squibb, Novartis, and AbbVie.

The effects of maribavir (Levtencity) for the treatment of resistant or refractory post-transplant cytomegalovirus (CMV) infection persisted at 52-week follow-up in hematopoietic stem cell and solid organ transplant patients from the pivotal phase 3 SOLSTICE trial.

Overall mortality in the 109 patients from these subcohorts from SOLSTICE was lower, compared with mortality reported for similar populations treated with conventional therapies used to treat relapsed or refractory (R/R) CMV, according to findings presented in April at the annual meeting of the European Society for Bone and Marrow Transplantation.

“These results, in addition to the superior efficacy in CMV clearance observed for maribavir in SOLSTICE provide supportive evidence of the potential for the long-term benefit of maribavir treatment for post-transplant CMV infection,” Ishan Hirji, of Takeda Development Center Americas, and colleagues reported during a poster session at the meeting.

A retrospective chart review of the 41 hematopoietic stem cell transplant (HSCT) patients and 68 solid organ transplant (SOT) patients randomized to receive maribavir showed an overall mortality rate of 15.6% at 52 weeks after initiation of treatment with the antiviral agent. Among the HSCT patients, 14 deaths occurred (34.1%), with 8 occurring during the study periods and 6 occurring during follow-up. Among the SOT patients, three deaths occurred (4.4%), all during follow-up chart review.

Causes of death included underlying disease relapse in four patients, infection other than CMV in six patients, and one case each of CMV-related factors, transplant-related factors, acute lymphoblastic leukemia, and septic shock. Causes of death in the SOT patients included one case each of CMV-related factors, anemia, and renal failure.

“No patients had new graft loss or retransplantation during the chart review period,” the investigators noted.

The findings are notable as CMV infection occurs in 30%-70% of HSCT recipients and 16%-56% of SOT recipients and can lead to complications, including transplant failure and death. Reported 1-year mortality rates following standard therapies for CMV range from 31% to 50%, they explained.

Patients in the SOLSTICE trial received 8 weeks of treatment and were followed for 12 additional weeks. CMV clearance at the end of treatment was 55.7% in the maribavir treatment arm versus 23.9% in a control group of patients treated with investigator choice of therapy. As reported by this news organization, the findings formed the basis for U.S. Food and Drug Administration approval of maribavir in November 2021.

The current analysis included a chart review period that started 1 day after the SOLSTICE trial period and continued for 32 additional weeks.

These long-term follow-up data confirm the benefits of maribavir for the treatment of post-transplant CMV, according to the investigators, and findings from a separate study reported at the ESBMT meeting underscore the importance of the durable benefits observed with maribavir treatment.

For that retrospective study, Maria Laura Fox, of Vall d’Hebron Institute of Oncology, Barcelona, and colleagues pooled de-identified data from 250 adult HSCT recipients with R/R CMV who were treated with agents other than maribavir at transplant centers in the United States or Europe. They aimed to “generate real-world evidence on the burden of CMV infection/disease in HSCT recipients who had refractory/resistant CMV or were intolerant to current treatments.”

Nearly 92% of patients received two or more therapies to treat CMV, and 92.2% discontinued treatment or had one or more therapy dose changes or discontinuation, and 42 patients failed to achieve clearance of the CMV index episode.

CMV recurred in 35.2% of patients, and graft failure occurred in 4% of patients, the investigators reported.

All-cause mortality was 56.0%, and mortality at 1 year after identification of R/R disease or treatment intolerance was 45.2%, they noted, adding that the study results “highlight the real-world complexities and high burden of CMV infection for HSCT recipients.”

“With available anti-CMV agents [excluding maribavir], a notable proportion of patients failed to achieve viremia clearance once developing RRI [resistant, refractory, or intolerant] CMV and/or experienced recurrence, and were at risk of adverse outcomes, including myelosuppression and mortality. There is a need for therapies that achieve and maintain CMV clearance with improved safety profiles,” they concluded.

Both studies were funded by Takeda Development Center Americas, the maker of Levtencity. Ms. Hirji is an employee of Takeda and reported stock ownership. Ms. Fox reported relationships with Sierra Oncology, GlaxoSmithKline, Bristol Myers Squibb, Novartis, and AbbVie.

The effects of maribavir (Levtencity) for the treatment of resistant or refractory post-transplant cytomegalovirus (CMV) infection persisted at 52-week follow-up in hematopoietic stem cell and solid organ transplant patients from the pivotal phase 3 SOLSTICE trial.

Overall mortality in the 109 patients from these subcohorts from SOLSTICE was lower, compared with mortality reported for similar populations treated with conventional therapies used to treat relapsed or refractory (R/R) CMV, according to findings presented in April at the annual meeting of the European Society for Bone and Marrow Transplantation.

“These results, in addition to the superior efficacy in CMV clearance observed for maribavir in SOLSTICE provide supportive evidence of the potential for the long-term benefit of maribavir treatment for post-transplant CMV infection,” Ishan Hirji, of Takeda Development Center Americas, and colleagues reported during a poster session at the meeting.

A retrospective chart review of the 41 hematopoietic stem cell transplant (HSCT) patients and 68 solid organ transplant (SOT) patients randomized to receive maribavir showed an overall mortality rate of 15.6% at 52 weeks after initiation of treatment with the antiviral agent. Among the HSCT patients, 14 deaths occurred (34.1%), with 8 occurring during the study periods and 6 occurring during follow-up. Among the SOT patients, three deaths occurred (4.4%), all during follow-up chart review.

Causes of death included underlying disease relapse in four patients, infection other than CMV in six patients, and one case each of CMV-related factors, transplant-related factors, acute lymphoblastic leukemia, and septic shock. Causes of death in the SOT patients included one case each of CMV-related factors, anemia, and renal failure.

“No patients had new graft loss or retransplantation during the chart review period,” the investigators noted.

The findings are notable as CMV infection occurs in 30%-70% of HSCT recipients and 16%-56% of SOT recipients and can lead to complications, including transplant failure and death. Reported 1-year mortality rates following standard therapies for CMV range from 31% to 50%, they explained.

Patients in the SOLSTICE trial received 8 weeks of treatment and were followed for 12 additional weeks. CMV clearance at the end of treatment was 55.7% in the maribavir treatment arm versus 23.9% in a control group of patients treated with investigator choice of therapy. As reported by this news organization, the findings formed the basis for U.S. Food and Drug Administration approval of maribavir in November 2021.

The current analysis included a chart review period that started 1 day after the SOLSTICE trial period and continued for 32 additional weeks.

These long-term follow-up data confirm the benefits of maribavir for the treatment of post-transplant CMV, according to the investigators, and findings from a separate study reported at the ESBMT meeting underscore the importance of the durable benefits observed with maribavir treatment.

For that retrospective study, Maria Laura Fox, of Vall d’Hebron Institute of Oncology, Barcelona, and colleagues pooled de-identified data from 250 adult HSCT recipients with R/R CMV who were treated with agents other than maribavir at transplant centers in the United States or Europe. They aimed to “generate real-world evidence on the burden of CMV infection/disease in HSCT recipients who had refractory/resistant CMV or were intolerant to current treatments.”

Nearly 92% of patients received two or more therapies to treat CMV, and 92.2% discontinued treatment or had one or more therapy dose changes or discontinuation, and 42 patients failed to achieve clearance of the CMV index episode.

CMV recurred in 35.2% of patients, and graft failure occurred in 4% of patients, the investigators reported.

All-cause mortality was 56.0%, and mortality at 1 year after identification of R/R disease or treatment intolerance was 45.2%, they noted, adding that the study results “highlight the real-world complexities and high burden of CMV infection for HSCT recipients.”

“With available anti-CMV agents [excluding maribavir], a notable proportion of patients failed to achieve viremia clearance once developing RRI [resistant, refractory, or intolerant] CMV and/or experienced recurrence, and were at risk of adverse outcomes, including myelosuppression and mortality. There is a need for therapies that achieve and maintain CMV clearance with improved safety profiles,” they concluded.

Both studies were funded by Takeda Development Center Americas, the maker of Levtencity. Ms. Hirji is an employee of Takeda and reported stock ownership. Ms. Fox reported relationships with Sierra Oncology, GlaxoSmithKline, Bristol Myers Squibb, Novartis, and AbbVie.

The immunotherapy blinatumomab improves short-term outcomes when added to standard chemotherapy for infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL), according to a report in the New England Journal of Medicine.

Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.

“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.

“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.

The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
 

Pediatric community responds

There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”

Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”

The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.

Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”

The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
 

Study details

Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.

The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m² per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.

Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.

Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.

There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.

There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.

Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.

The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.

The immunotherapy blinatumomab improves short-term outcomes when added to standard chemotherapy for infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL), according to a report in the New England Journal of Medicine.

Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.

“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.

“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.

The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
 

Pediatric community responds

There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”

Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”

The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.

Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”

The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
 

Study details

Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.

The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m² per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.

Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.

Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.

There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.

There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.

Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.

The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.

The immunotherapy blinatumomab improves short-term outcomes when added to standard chemotherapy for infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL), according to a report in the New England Journal of Medicine.

Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.

“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.

“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.

The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
 

Pediatric community responds

There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”

Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”

The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.

Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”

The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
 

Study details

Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.

The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m² per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.

Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.

Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.

There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.

There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.

Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.

The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.

Ponatinib, a potent third-generation tyrosine kinase inhibitor (TKI), showed superior efficacy and comparable safety versus the first-generation TKI imatinib in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL).

The agents were evaluated in the randomized, open-label, phase 3 PhALLCON study, the first head-to-head comparison of ponatinib and imatinib in combination with reduced-intensity chemotherapy in the Ph+ALL population.

Overall, patients in the ponatinib arm experienced a significantly higher minimal residual disease (MRD)–negative complete response rate as well as deeper and more durable responses compared with those in the imatinib arm, the investigators reported.

The findings were presented during an American Society of Clinical Oncology virtual plenary session.

In adults with ALL, Ph+ disease is the most frequent genetic subtype, accounting for about one third of cases. The current standard of care for newly diagnosed Ph+ALL, also known as BCR-ABL-1–positive ALL, is BCR-ABL1 TKIs in combination with chemotherapy or steroids. However, when treated with first- or second-generation TKIs, patients eventually progress due to the emergence of treatment resistance.

Before the advent of TKI therapies, Ph+ALL had a very poor prognosis, but the development of imatinib in 2001 was transformative, said Marlise R. Luskin, MD, a senior physician at Dana-Farber Cancer Institute, Boston, in the ASCO plenary session, exploring the state of the science.

Added to “backbone” chemotherapy regimens, imatinib improved complete response rates, increased eligibility for stem cell transplantation, and improved overall survival. Second-generation TKIs, including dasatinib and nilotinib further improved outcomes, said Dr. Luskin, also assistant professor at Harvard Medical School, Boston.

More recently, ponatinib has emerged as a promising treatment given its unique action against the ABLA1 T315I KD mutation present in about 75% of cases that relapse as well as the findings of improved MRD-negative complete response rates and event-free survival in retrospective studies, Dr. Luskin said.

The PhALLCON study was designed to further investigate promising results seen in retrospective studies of ponatinib.

To assess ponatinib versus imatinib, patients were enrolled and randomized two to one to receive either a 30-mg once-daily starting dose of ponatinib or a once-daily 600 mg dose of imatinib plus reduced-intensity chemotherapy. After cycle 20, patients received single agent ponatinib or imatinib until disease progression or unacceptable toxicity.

Of the 245 enrolled, 78 remained on treatment at the August 2022 data cutoff, including 42% of those in the ponatinib arm and 12% in the imatinib arm. The most common reasons for discontinuation included hematopoietic stem cell transplantation (31% for ponatinib and 37% for imatinib), adverse events (12% in both arms), and lack of efficacy (7% and 26%, respectively).

At median follow-up of 20 months among 164 patients in the ponatinib arm and 18 months among 81 patients in the imatinib arm, the MRD-negative complete response rates were 34.4% and 16.7%, respectively, said first author Elias J. Jabbour, MD, a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.

A trend toward improved event-free survival was also observed in the ponatinib arm, but the data were not mature at the time of the analysis, Dr. Jabbour noted.

The two treatments showed comparable safety. Treatment-emergent adverse event rates of any grade and of grade 3 or higher were similar in the two study arms. Arterial occlusive events were infrequent and were also similar between the arms.

“Taken together, for this patient population, the efficacy and safety results demonstrate a favorable risk-benefit assessment for ponatinib, which should be considered a standard of care for frontline therapy in patents with newly diagnosed Ph+ALL,” Dr. Jabbour said.

Although the PhALLCON findings are encouraging, invited discussant Anjali S. Advani, MD, of the Cleveland Clinic, noted some study “pitfalls and caveats,” including the generally younger age and low incidence of cardiovascular risk factors in the study population, which raises questions about the ability to extrapolate the findings to “the larger population, which may be older and have more comorbidities.”

Dr. Advani also said that the ponatinib versus imatinib comparison is a reasonable one, but that most clinicians are now using dasatinib, so “it would have been nice to have this comparison.”

Additionally, “the landscape is now changing with the use of blinatumomab plus TKIs – either dasatinib or ponatinib – in the up-front setting.”

“There is data now from various groups ... showing excellent results, although longer follow-up is needed on all of these,” she said.

One such study is the GIMEMA ALL2820 trial looking at ponatinib plus blinatumomab versus imatinib plus chemotherapy, said Nicolas Boissel, MD, PhD, of Hôpital Saint-Louis in Paris, an invited discussant who addressed the European perspective on the PhALLCON results.

“It is expected that access to ponatinib will be delayed in Europe, compared with the U.S., so meanwhile, clinical trials remain a good option to give access to ponatinib frontline,” he said.

Going forward, Dr. Boissel said it will be important to determine the role of second-generation TKIs in patients who are ineligible to receive ponatinib, the treatment duration needed to reduce long-term risk of relapse, and the potential for eliminating the need for postremission chemotherapy and stem cell transplantation in certain patients.

Dr. Advani added that when evaluating and comparing treatments, it will be important to look at genomic alterations and BCR-ABL mutation status, age and comorbidities, and patterns of disease relapse, including relapse sites and genomics. Longer follow-up results for event-free survival and overall survival are also needed.

“I think, particularly in younger patients with relatively few or no cardiovascular comorbidities, [ponatinib plus reduced-intensity chemotherapy] represents a really exciting option,” Dr. Advani said. “What’s difficult is that the landscape is changing quickly in this field, and so is the standard of care. I think what we struggle with is whether we should be using antibody-based therapies plus TKIs or look at an approach such as this, and further studies are going to be needed to answer that question.”

Dr. Jabbour disclosed ties with Pfizer, Takeda, Amgen, AbbVie, Bristol-Myers Squibb, Incyte, Adaptive Biotechnologies, Astellas Pharma, Genentech, and Ascentage Pharma. Dr. Luskin reported relationships with Pfizer, Novartis, and Abbvie. Dr. Advani disclosed ties with Novartis, Glycomimetics, Kite Pharma, Seattle Genetics, Amgen, Beam Therapeutics, Mkarta, Taiho Oncology, Jazz Pharmaceuticals, Pfizer, and Kura Oncology. Dr. Boissel reported relationships with Amgen, ARIAD/Incyte, Novartis, SERVIER, and Astellas Pharma.

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

Ponatinib, a potent third-generation tyrosine kinase inhibitor (TKI), showed superior efficacy and comparable safety versus the first-generation TKI imatinib in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL).

The agents were evaluated in the randomized, open-label, phase 3 PhALLCON study, the first head-to-head comparison of ponatinib and imatinib in combination with reduced-intensity chemotherapy in the Ph+ALL population.

Overall, patients in the ponatinib arm experienced a significantly higher minimal residual disease (MRD)–negative complete response rate as well as deeper and more durable responses compared with those in the imatinib arm, the investigators reported.

The findings were presented during an American Society of Clinical Oncology virtual plenary session.

In adults with ALL, Ph+ disease is the most frequent genetic subtype, accounting for about one third of cases. The current standard of care for newly diagnosed Ph+ALL, also known as BCR-ABL-1–positive ALL, is BCR-ABL1 TKIs in combination with chemotherapy or steroids. However, when treated with first- or second-generation TKIs, patients eventually progress due to the emergence of treatment resistance.

Before the advent of TKI therapies, Ph+ALL had a very poor prognosis, but the development of imatinib in 2001 was transformative, said Marlise R. Luskin, MD, a senior physician at Dana-Farber Cancer Institute, Boston, in the ASCO plenary session, exploring the state of the science.

Added to “backbone” chemotherapy regimens, imatinib improved complete response rates, increased eligibility for stem cell transplantation, and improved overall survival. Second-generation TKIs, including dasatinib and nilotinib further improved outcomes, said Dr. Luskin, also assistant professor at Harvard Medical School, Boston.

More recently, ponatinib has emerged as a promising treatment given its unique action against the ABLA1 T315I KD mutation present in about 75% of cases that relapse as well as the findings of improved MRD-negative complete response rates and event-free survival in retrospective studies, Dr. Luskin said.

The PhALLCON study was designed to further investigate promising results seen in retrospective studies of ponatinib.

To assess ponatinib versus imatinib, patients were enrolled and randomized two to one to receive either a 30-mg once-daily starting dose of ponatinib or a once-daily 600 mg dose of imatinib plus reduced-intensity chemotherapy. After cycle 20, patients received single agent ponatinib or imatinib until disease progression or unacceptable toxicity.

Of the 245 enrolled, 78 remained on treatment at the August 2022 data cutoff, including 42% of those in the ponatinib arm and 12% in the imatinib arm. The most common reasons for discontinuation included hematopoietic stem cell transplantation (31% for ponatinib and 37% for imatinib), adverse events (12% in both arms), and lack of efficacy (7% and 26%, respectively).

At median follow-up of 20 months among 164 patients in the ponatinib arm and 18 months among 81 patients in the imatinib arm, the MRD-negative complete response rates were 34.4% and 16.7%, respectively, said first author Elias J. Jabbour, MD, a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.

A trend toward improved event-free survival was also observed in the ponatinib arm, but the data were not mature at the time of the analysis, Dr. Jabbour noted.

The two treatments showed comparable safety. Treatment-emergent adverse event rates of any grade and of grade 3 or higher were similar in the two study arms. Arterial occlusive events were infrequent and were also similar between the arms.

“Taken together, for this patient population, the efficacy and safety results demonstrate a favorable risk-benefit assessment for ponatinib, which should be considered a standard of care for frontline therapy in patents with newly diagnosed Ph+ALL,” Dr. Jabbour said.

Although the PhALLCON findings are encouraging, invited discussant Anjali S. Advani, MD, of the Cleveland Clinic, noted some study “pitfalls and caveats,” including the generally younger age and low incidence of cardiovascular risk factors in the study population, which raises questions about the ability to extrapolate the findings to “the larger population, which may be older and have more comorbidities.”

Dr. Advani also said that the ponatinib versus imatinib comparison is a reasonable one, but that most clinicians are now using dasatinib, so “it would have been nice to have this comparison.”

Additionally, “the landscape is now changing with the use of blinatumomab plus TKIs – either dasatinib or ponatinib – in the up-front setting.”

“There is data now from various groups ... showing excellent results, although longer follow-up is needed on all of these,” she said.

One such study is the GIMEMA ALL2820 trial looking at ponatinib plus blinatumomab versus imatinib plus chemotherapy, said Nicolas Boissel, MD, PhD, of Hôpital Saint-Louis in Paris, an invited discussant who addressed the European perspective on the PhALLCON results.

“It is expected that access to ponatinib will be delayed in Europe, compared with the U.S., so meanwhile, clinical trials remain a good option to give access to ponatinib frontline,” he said.

Going forward, Dr. Boissel said it will be important to determine the role of second-generation TKIs in patients who are ineligible to receive ponatinib, the treatment duration needed to reduce long-term risk of relapse, and the potential for eliminating the need for postremission chemotherapy and stem cell transplantation in certain patients.

Dr. Advani added that when evaluating and comparing treatments, it will be important to look at genomic alterations and BCR-ABL mutation status, age and comorbidities, and patterns of disease relapse, including relapse sites and genomics. Longer follow-up results for event-free survival and overall survival are also needed.

“I think, particularly in younger patients with relatively few or no cardiovascular comorbidities, [ponatinib plus reduced-intensity chemotherapy] represents a really exciting option,” Dr. Advani said. “What’s difficult is that the landscape is changing quickly in this field, and so is the standard of care. I think what we struggle with is whether we should be using antibody-based therapies plus TKIs or look at an approach such as this, and further studies are going to be needed to answer that question.”

Dr. Jabbour disclosed ties with Pfizer, Takeda, Amgen, AbbVie, Bristol-Myers Squibb, Incyte, Adaptive Biotechnologies, Astellas Pharma, Genentech, and Ascentage Pharma. Dr. Luskin reported relationships with Pfizer, Novartis, and Abbvie. Dr. Advani disclosed ties with Novartis, Glycomimetics, Kite Pharma, Seattle Genetics, Amgen, Beam Therapeutics, Mkarta, Taiho Oncology, Jazz Pharmaceuticals, Pfizer, and Kura Oncology. Dr. Boissel reported relationships with Amgen, ARIAD/Incyte, Novartis, SERVIER, and Astellas Pharma.

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

Ponatinib, a potent third-generation tyrosine kinase inhibitor (TKI), showed superior efficacy and comparable safety versus the first-generation TKI imatinib in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL).

The agents were evaluated in the randomized, open-label, phase 3 PhALLCON study, the first head-to-head comparison of ponatinib and imatinib in combination with reduced-intensity chemotherapy in the Ph+ALL population.

Overall, patients in the ponatinib arm experienced a significantly higher minimal residual disease (MRD)–negative complete response rate as well as deeper and more durable responses compared with those in the imatinib arm, the investigators reported.

The findings were presented during an American Society of Clinical Oncology virtual plenary session.

In adults with ALL, Ph+ disease is the most frequent genetic subtype, accounting for about one third of cases. The current standard of care for newly diagnosed Ph+ALL, also known as BCR-ABL-1–positive ALL, is BCR-ABL1 TKIs in combination with chemotherapy or steroids. However, when treated with first- or second-generation TKIs, patients eventually progress due to the emergence of treatment resistance.

Before the advent of TKI therapies, Ph+ALL had a very poor prognosis, but the development of imatinib in 2001 was transformative, said Marlise R. Luskin, MD, a senior physician at Dana-Farber Cancer Institute, Boston, in the ASCO plenary session, exploring the state of the science.

Added to “backbone” chemotherapy regimens, imatinib improved complete response rates, increased eligibility for stem cell transplantation, and improved overall survival. Second-generation TKIs, including dasatinib and nilotinib further improved outcomes, said Dr. Luskin, also assistant professor at Harvard Medical School, Boston.

More recently, ponatinib has emerged as a promising treatment given its unique action against the ABLA1 T315I KD mutation present in about 75% of cases that relapse as well as the findings of improved MRD-negative complete response rates and event-free survival in retrospective studies, Dr. Luskin said.

The PhALLCON study was designed to further investigate promising results seen in retrospective studies of ponatinib.

To assess ponatinib versus imatinib, patients were enrolled and randomized two to one to receive either a 30-mg once-daily starting dose of ponatinib or a once-daily 600 mg dose of imatinib plus reduced-intensity chemotherapy. After cycle 20, patients received single agent ponatinib or imatinib until disease progression or unacceptable toxicity.

Of the 245 enrolled, 78 remained on treatment at the August 2022 data cutoff, including 42% of those in the ponatinib arm and 12% in the imatinib arm. The most common reasons for discontinuation included hematopoietic stem cell transplantation (31% for ponatinib and 37% for imatinib), adverse events (12% in both arms), and lack of efficacy (7% and 26%, respectively).

At median follow-up of 20 months among 164 patients in the ponatinib arm and 18 months among 81 patients in the imatinib arm, the MRD-negative complete response rates were 34.4% and 16.7%, respectively, said first author Elias J. Jabbour, MD, a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.

A trend toward improved event-free survival was also observed in the ponatinib arm, but the data were not mature at the time of the analysis, Dr. Jabbour noted.

The two treatments showed comparable safety. Treatment-emergent adverse event rates of any grade and of grade 3 or higher were similar in the two study arms. Arterial occlusive events were infrequent and were also similar between the arms.

“Taken together, for this patient population, the efficacy and safety results demonstrate a favorable risk-benefit assessment for ponatinib, which should be considered a standard of care for frontline therapy in patents with newly diagnosed Ph+ALL,” Dr. Jabbour said.

Although the PhALLCON findings are encouraging, invited discussant Anjali S. Advani, MD, of the Cleveland Clinic, noted some study “pitfalls and caveats,” including the generally younger age and low incidence of cardiovascular risk factors in the study population, which raises questions about the ability to extrapolate the findings to “the larger population, which may be older and have more comorbidities.”

Dr. Advani also said that the ponatinib versus imatinib comparison is a reasonable one, but that most clinicians are now using dasatinib, so “it would have been nice to have this comparison.”

Additionally, “the landscape is now changing with the use of blinatumomab plus TKIs – either dasatinib or ponatinib – in the up-front setting.”

“There is data now from various groups ... showing excellent results, although longer follow-up is needed on all of these,” she said.

One such study is the GIMEMA ALL2820 trial looking at ponatinib plus blinatumomab versus imatinib plus chemotherapy, said Nicolas Boissel, MD, PhD, of Hôpital Saint-Louis in Paris, an invited discussant who addressed the European perspective on the PhALLCON results.

“It is expected that access to ponatinib will be delayed in Europe, compared with the U.S., so meanwhile, clinical trials remain a good option to give access to ponatinib frontline,” he said.

Going forward, Dr. Boissel said it will be important to determine the role of second-generation TKIs in patients who are ineligible to receive ponatinib, the treatment duration needed to reduce long-term risk of relapse, and the potential for eliminating the need for postremission chemotherapy and stem cell transplantation in certain patients.

Dr. Advani added that when evaluating and comparing treatments, it will be important to look at genomic alterations and BCR-ABL mutation status, age and comorbidities, and patterns of disease relapse, including relapse sites and genomics. Longer follow-up results for event-free survival and overall survival are also needed.

“I think, particularly in younger patients with relatively few or no cardiovascular comorbidities, [ponatinib plus reduced-intensity chemotherapy] represents a really exciting option,” Dr. Advani said. “What’s difficult is that the landscape is changing quickly in this field, and so is the standard of care. I think what we struggle with is whether we should be using antibody-based therapies plus TKIs or look at an approach such as this, and further studies are going to be needed to answer that question.”

Dr. Jabbour disclosed ties with Pfizer, Takeda, Amgen, AbbVie, Bristol-Myers Squibb, Incyte, Adaptive Biotechnologies, Astellas Pharma, Genentech, and Ascentage Pharma. Dr. Luskin reported relationships with Pfizer, Novartis, and Abbvie. Dr. Advani disclosed ties with Novartis, Glycomimetics, Kite Pharma, Seattle Genetics, Amgen, Beam Therapeutics, Mkarta, Taiho Oncology, Jazz Pharmaceuticals, Pfizer, and Kura Oncology. Dr. Boissel reported relationships with Amgen, ARIAD/Incyte, Novartis, SERVIER, and Astellas Pharma.

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

If you could go back in time 75 years and tell Dr. Sidney Farber, the developer of methotrexate for cancer therapy, that 21st-century medicine would utilize his specially designed drug more in rheumatology than oncology, he might be surprised. He might scratch his head even more, hearing of his drug sparking interest in still other medical fields, like cardiology.

But drug repurposing is not so uncommon. One classic example is aspirin. Once the most common pain medication and used also in rheumatology, aspirin now finds a range of applications, from colorectal cancer to the prevention of cardiovascular and cerebrovascular thrombosis. Minoxidil is another example, developed for hypertension but used today mostly to stop hair loss. Perhaps most ironic is thalidomide, utilized today for leprosy and multiple myeloma, yet actually contraindicated for its original application, nausea of pregnancy.

Courtesy NIH

Methotrexate, thus, has much in common with other medical treatments, and yet its origin story is as unique and as fascinating as the story of Dr. Farber himself. While this is a rheumatology article, it’s also a story about the origin of a particular rheumatologic treatment, and so the story of that origin will take us mostly through a discussion of hematologic malignancy and of the clinical researcher who dared search for a cure.

Born in 1903, in Buffalo, New York, third of fourteen children of Jewish immigrants from Poland, Dr. Farber grew up in a household that was crowded but academically rigorous. His father, Simon, routinely brought home textbooks, assigning each child a book to read and on which to write a report. His mother, Matilda, was as devoted as her husband to raising the children to succeed in their adopted new country. Upstairs, the children were permitted to speak Yiddish, but downstairs they were required to use only English and German.

As a teen, Dr. Farber lived through the 1918 influenza pandemic that killed at least 50 million people worldwide, including more than 2,000 Buffalonians. This probably helped motivate him to study medicine, but with antisemitism overt in the America of the early 1920s, securing admission to a U.S. medical school was close to impossible. So, in what now seems like the greatest of ironies, Dr. Farber began medical studies in Germany, then transferred for the second year to a U.S. program that seemed adequate – Harvard Medical School, from which he graduated in 1927. From there, he trained as a pathologist, focusing ultimately on pediatric pathology. But, frustrated by case after case of malignancy, whose young victims he’d often have to autopsy, Dr. Farber decided that he wanted to advance the pitiful state of cancer therapeutics, especially for hematologic malignancy.

This was a tall order in the 1930s and early 1940s, when cancer therapeutics consisted only of surgical resection and very primitive forms of radiation therapy. Applicable only to neoplasia that was localized, these options were useless against malignancies in the blood, like acute lymphoblastic leukemia (ALL), but by January 1948 there was at least one glimmer of hope. At that time, one patient with ALL, 2-year-old Robert Sandler, was too ill to join his twin brother Elliott for snow play outside their home in the Dorchester section of Boston. Diagnosed back in August, Robert had suffered multiple episodes of fever, anemia, and thrombocytopenia. His illness had enlarged his spleen dramatically and caused pathologic bone fractures with excruciating bone pain, and for a while he couldn’t walk because of pressure on his lower spinal cord. All of this was the result of uncontrolled mitosis and cell division of lymphoblasts, immature lymphocytes. By December, these out-of-control cells had elevated the boy’s white blood cell count to a peak of 70,000/mcL, more than six times the high end of the normal range (4,500-11,000/mcL). This had happened despite treatment with an experimental drug, developed at Boston Children’s Hospital by Dr. Farber and his team, working on the assumption that inhibition of folate metabolism should slow the growth of tumor cells. On Dec. 28, however, Dr. Farber had switched the child to a new drug with a chemical structure just slightly different from the other agent’s.

Merely another chemical modification in a series of attempts by the research team, the new drug, aminopterin, was not expected to do anything dramatic, but Dr. Farber and the team had come such a long way since the middle of 1947, when he’d actually done the opposite of what he was doing now. On the basis of British research from India showing folic acid deficiency as the basis of a common type of anemia in malnourished people, Dr. Farber had reasoned that children with leukemia, who also suffered from anemia, might also benefit from folic acid supplementation. Even without prior rodent testing, Dr. Farber had tried giving the nutrient to patients with ALL, a strategy made possible by the presence of a spectacular chemist working on folic acid synthesis at Farber’s own hospital to help combat folate deficiency. Born into a poor Brahmin family in India, the chemist, Dr. Yellapragada SubbaRow, had begun life with so much stacked against him as to appear even less likely during childhood than the young Dr. Farber to grow up to make major contributions to medicine. Going through childhood with death all around him, Dr. SubbaRow was motivated to study medicine, but getting into medical school had been an uphill fight, given his family’s economic difficulty. Knowing that he’d also face discrimination on account of his low status after receiving admission to a medical program, SubbaRow could have made things a bit easier for himself by living within the norms of the British Imperial system, but as a supporter of Mohandas Gandhi’s nationalist movement, he boycotted British goods. As a medical student, this meant doing things like wearing Indian-made surgical gloves, instead of the English products that were expected of the students. Such actions led Dr. SubbaRow to receive a kind of second-rate medical degree, rather than the prestigious MBBS.

The political situation also led Dr. SubbaRow to emigrate to the United States, where, ironically, his medical degree initially was taken less seriously than it had been taken in his British-occupied homeland. He thus worked in the capacity of a hospital night porter at Peter Bent Brigham Hospital (the future Brigham and Women’s Hospital), doing menial tasks like changing sheets to make ends meet. He studied, however, and made enough of an impression to gain admission to the same institution that also admitted Farber through the backdoor, Harvard Medical School. This launched him into a research career in which he not only would be instrumental in developing folate antagonists and other classes of drugs, but also would make him the codiscoverer of the role of creatine phosphate and ATP in cellular energy metabolism. Sadly, even after obtaining his top-notch American credentials and contributing through his research to what you might say is a good chunk of the biochemistry pathways that first year medical students memorize without ever learning who discovered them, Dr. SubbaRow still faced prejudice for the rest of his life, which turned out to last only until the age of 53. To add insult to injury, he is rarely remembered for his role.

Dr. Farber proceeded with the folic acid supplementation idea in patients with ALL, even though ALL caused a hypoproliferative anemia, whereas anemia from folate deficiency was megaloblastic, meaning that erythrocytes were produced but they were oversized and dysfunctional. Tragically, folic acid had accelerated the disease process in children with ALL, but the process of chemical experimentation aimed at synthesizing folate also produced some compounds that mimicked chemical precursors of folate in a way that made them antifolates, inhibitors of folate metabolism. If folic acid made lymphoblasts grow faster, Dr. Farber had reasoned that antifolates should inhibit their growth. He thus asked the chemistry lab to focus on folate inhibitors. Testing aminopterin, beginning with young Robert Sandler at the end of December, is what proved his hypothesis correct. By late January, aminopterin had brought the child’s WBC count down to the realm of 12,000, just slightly above normal, with symptoms and signs abating as well, and by February, the child could play with his twin brother. It was not a cure; malignant lymphoblasts still showed on microscopy of Robert’s blood. While he and some 15 other children whom Dr. Farber treated in this early trial would all succumb to ALL, they experienced remission lasting several months.

This was a big deal because the concept of chemotherapy was based only on serendipitous observations of WBC counts dropping in soldiers exposed to nitrogen mustard gas during World War I and during an incident in World War II, yet aminopterin had been designed from the ground up. Though difficult to synthesize in quantities, there was no reason for Dr. Farber’s team not to keep tweaking the drug, and so they did. Replacing one hydrogen atom with a methyl group, they turned it into methotrexate.

Proving easier to synthesize and less toxic, methotrexate would become a workhorse for chemotherapy over the next couple of decades, but the capability of both methotrexate and aminopterin to blunt the growth of white blood cells and other cells did not go unnoticed outside the realm of oncology. As early as the 1950s, dermatologists were using aminopterin to treat psoriasis. This led to the approval of methotrexate for psoriasis in 1972.

Meanwhile, like oncology, infectious diseases, aviation medicine, and so many other areas of practice, rheumatology had gotten a major boost from research stemming from World War II. During the war, Dr. Philip Hench of the Mayo Clinic developed cortisone, which pilots used to stay alert and energetic during trans-Atlantic flights. But it turned out that cortisone had a powerful immunosuppressive effect that dramatically improved rheumatoid arthritis, leading Dr. Hench to receive the Nobel Prize in Physiology or Medicine in 1950. By the end of the 1950s, however, the significant side effects of long-term corticosteroid therapy were very clear, so over the next few decades there was a major effort to develop different treatments for RA and other rheumatologic diseases.

Top on the list of such agents was methotrexate, developed for RA in part by Dr. Michael Weinblatt of Brigham and Women’s Hospital in Boston. In the 1980s, Dr. Weinblatt published the first clinical trial showing the benefits of methotrexate for RA patients. This has since developed into a standard treatment, noticeably different from the original malignancy application in that it is a low-dose regimen. Patients taking methotrexate for RA typically receive no more than 25 mg per week orally, and often much less. Rheumatology today includes expertise in keeping long-term methotrexate therapy safe by monitoring liver function and through other routine tests. The routine nature of the therapy has brought methotrexate to the point of beckoning in a realm that Dr. Farber might not have predicted in his wildest imagination: cardiology. This is on account of the growing appreciation of the inflammatory process in the pathophysiology of atherosclerotic heart disease.

Meanwhile, being an antimetabolite, harmful to rapidly dividing cells, the danger of methotrexate to the embryo and fetus was recognized early. This made methotrexate off-limits to pregnant women, yet it also has made the drug useful as an abortifacient. Though not as good for medication abortion in unwanted but thriving pregnancies, where mifepristone/misoprostol has become the regimen of choice, methotrexate has become a workhorse in other obstetrical settings, such as for ending ectopic pregnancy.

Looking at the present and into the future, the potential for this very old medication looks wide open, as if it could go in any direction, so let’s wind up the discussion with the thought that we may be in for some surprises. Rather than jumping deeply into any rheumatologic issue, we spent most of this article weaving through other medical issues, but does this not make today’s story fairly analogous to rheumatology itself?

Dr. Warmflash is a physician from Portland, Ore. He reported no conflicts of interest.

This story was updated 2/10/2023.

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

If you could go back in time 75 years and tell Dr. Sidney Farber, the developer of methotrexate for cancer therapy, that 21st-century medicine would utilize his specially designed drug more in rheumatology than oncology, he might be surprised. He might scratch his head even more, hearing of his drug sparking interest in still other medical fields, like cardiology.

But drug repurposing is not so uncommon. One classic example is aspirin. Once the most common pain medication and used also in rheumatology, aspirin now finds a range of applications, from colorectal cancer to the prevention of cardiovascular and cerebrovascular thrombosis. Minoxidil is another example, developed for hypertension but used today mostly to stop hair loss. Perhaps most ironic is thalidomide, utilized today for leprosy and multiple myeloma, yet actually contraindicated for its original application, nausea of pregnancy.

Courtesy NIH

Methotrexate, thus, has much in common with other medical treatments, and yet its origin story is as unique and as fascinating as the story of Dr. Farber himself. While this is a rheumatology article, it’s also a story about the origin of a particular rheumatologic treatment, and so the story of that origin will take us mostly through a discussion of hematologic malignancy and of the clinical researcher who dared search for a cure.

Born in 1903, in Buffalo, New York, third of fourteen children of Jewish immigrants from Poland, Dr. Farber grew up in a household that was crowded but academically rigorous. His father, Simon, routinely brought home textbooks, assigning each child a book to read and on which to write a report. His mother, Matilda, was as devoted as her husband to raising the children to succeed in their adopted new country. Upstairs, the children were permitted to speak Yiddish, but downstairs they were required to use only English and German.

As a teen, Dr. Farber lived through the 1918 influenza pandemic that killed at least 50 million people worldwide, including more than 2,000 Buffalonians. This probably helped motivate him to study medicine, but with antisemitism overt in the America of the early 1920s, securing admission to a U.S. medical school was close to impossible. So, in what now seems like the greatest of ironies, Dr. Farber began medical studies in Germany, then transferred for the second year to a U.S. program that seemed adequate – Harvard Medical School, from which he graduated in 1927. From there, he trained as a pathologist, focusing ultimately on pediatric pathology. But, frustrated by case after case of malignancy, whose young victims he’d often have to autopsy, Dr. Farber decided that he wanted to advance the pitiful state of cancer therapeutics, especially for hematologic malignancy.

This was a tall order in the 1930s and early 1940s, when cancer therapeutics consisted only of surgical resection and very primitive forms of radiation therapy. Applicable only to neoplasia that was localized, these options were useless against malignancies in the blood, like acute lymphoblastic leukemia (ALL), but by January 1948 there was at least one glimmer of hope. At that time, one patient with ALL, 2-year-old Robert Sandler, was too ill to join his twin brother Elliott for snow play outside their home in the Dorchester section of Boston. Diagnosed back in August, Robert had suffered multiple episodes of fever, anemia, and thrombocytopenia. His illness had enlarged his spleen dramatically and caused pathologic bone fractures with excruciating bone pain, and for a while he couldn’t walk because of pressure on his lower spinal cord. All of this was the result of uncontrolled mitosis and cell division of lymphoblasts, immature lymphocytes. By December, these out-of-control cells had elevated the boy’s white blood cell count to a peak of 70,000/mcL, more than six times the high end of the normal range (4,500-11,000/mcL). This had happened despite treatment with an experimental drug, developed at Boston Children’s Hospital by Dr. Farber and his team, working on the assumption that inhibition of folate metabolism should slow the growth of tumor cells. On Dec. 28, however, Dr. Farber had switched the child to a new drug with a chemical structure just slightly different from the other agent’s.

Merely another chemical modification in a series of attempts by the research team, the new drug, aminopterin, was not expected to do anything dramatic, but Dr. Farber and the team had come such a long way since the middle of 1947, when he’d actually done the opposite of what he was doing now. On the basis of British research from India showing folic acid deficiency as the basis of a common type of anemia in malnourished people, Dr. Farber had reasoned that children with leukemia, who also suffered from anemia, might also benefit from folic acid supplementation. Even without prior rodent testing, Dr. Farber had tried giving the nutrient to patients with ALL, a strategy made possible by the presence of a spectacular chemist working on folic acid synthesis at Farber’s own hospital to help combat folate deficiency. Born into a poor Brahmin family in India, the chemist, Dr. Yellapragada SubbaRow, had begun life with so much stacked against him as to appear even less likely during childhood than the young Dr. Farber to grow up to make major contributions to medicine. Going through childhood with death all around him, Dr. SubbaRow was motivated to study medicine, but getting into medical school had been an uphill fight, given his family’s economic difficulty. Knowing that he’d also face discrimination on account of his low status after receiving admission to a medical program, SubbaRow could have made things a bit easier for himself by living within the norms of the British Imperial system, but as a supporter of Mohandas Gandhi’s nationalist movement, he boycotted British goods. As a medical student, this meant doing things like wearing Indian-made surgical gloves, instead of the English products that were expected of the students. Such actions led Dr. SubbaRow to receive a kind of second-rate medical degree, rather than the prestigious MBBS.

The political situation also led Dr. SubbaRow to emigrate to the United States, where, ironically, his medical degree initially was taken less seriously than it had been taken in his British-occupied homeland. He thus worked in the capacity of a hospital night porter at Peter Bent Brigham Hospital (the future Brigham and Women’s Hospital), doing menial tasks like changing sheets to make ends meet. He studied, however, and made enough of an impression to gain admission to the same institution that also admitted Farber through the backdoor, Harvard Medical School. This launched him into a research career in which he not only would be instrumental in developing folate antagonists and other classes of drugs, but also would make him the codiscoverer of the role of creatine phosphate and ATP in cellular energy metabolism. Sadly, even after obtaining his top-notch American credentials and contributing through his research to what you might say is a good chunk of the biochemistry pathways that first year medical students memorize without ever learning who discovered them, Dr. SubbaRow still faced prejudice for the rest of his life, which turned out to last only until the age of 53. To add insult to injury, he is rarely remembered for his role.

Dr. Farber proceeded with the folic acid supplementation idea in patients with ALL, even though ALL caused a hypoproliferative anemia, whereas anemia from folate deficiency was megaloblastic, meaning that erythrocytes were produced but they were oversized and dysfunctional. Tragically, folic acid had accelerated the disease process in children with ALL, but the process of chemical experimentation aimed at synthesizing folate also produced some compounds that mimicked chemical precursors of folate in a way that made them antifolates, inhibitors of folate metabolism. If folic acid made lymphoblasts grow faster, Dr. Farber had reasoned that antifolates should inhibit their growth. He thus asked the chemistry lab to focus on folate inhibitors. Testing aminopterin, beginning with young Robert Sandler at the end of December, is what proved his hypothesis correct. By late January, aminopterin had brought the child’s WBC count down to the realm of 12,000, just slightly above normal, with symptoms and signs abating as well, and by February, the child could play with his twin brother. It was not a cure; malignant lymphoblasts still showed on microscopy of Robert’s blood. While he and some 15 other children whom Dr. Farber treated in this early trial would all succumb to ALL, they experienced remission lasting several months.

This was a big deal because the concept of chemotherapy was based only on serendipitous observations of WBC counts dropping in soldiers exposed to nitrogen mustard gas during World War I and during an incident in World War II, yet aminopterin had been designed from the ground up. Though difficult to synthesize in quantities, there was no reason for Dr. Farber’s team not to keep tweaking the drug, and so they did. Replacing one hydrogen atom with a methyl group, they turned it into methotrexate.

Proving easier to synthesize and less toxic, methotrexate would become a workhorse for chemotherapy over the next couple of decades, but the capability of both methotrexate and aminopterin to blunt the growth of white blood cells and other cells did not go unnoticed outside the realm of oncology. As early as the 1950s, dermatologists were using aminopterin to treat psoriasis. This led to the approval of methotrexate for psoriasis in 1972.

Meanwhile, like oncology, infectious diseases, aviation medicine, and so many other areas of practice, rheumatology had gotten a major boost from research stemming from World War II. During the war, Dr. Philip Hench of the Mayo Clinic developed cortisone, which pilots used to stay alert and energetic during trans-Atlantic flights. But it turned out that cortisone had a powerful immunosuppressive effect that dramatically improved rheumatoid arthritis, leading Dr. Hench to receive the Nobel Prize in Physiology or Medicine in 1950. By the end of the 1950s, however, the significant side effects of long-term corticosteroid therapy were very clear, so over the next few decades there was a major effort to develop different treatments for RA and other rheumatologic diseases.

Top on the list of such agents was methotrexate, developed for RA in part by Dr. Michael Weinblatt of Brigham and Women’s Hospital in Boston. In the 1980s, Dr. Weinblatt published the first clinical trial showing the benefits of methotrexate for RA patients. This has since developed into a standard treatment, noticeably different from the original malignancy application in that it is a low-dose regimen. Patients taking methotrexate for RA typically receive no more than 25 mg per week orally, and often much less. Rheumatology today includes expertise in keeping long-term methotrexate therapy safe by monitoring liver function and through other routine tests. The routine nature of the therapy has brought methotrexate to the point of beckoning in a realm that Dr. Farber might not have predicted in his wildest imagination: cardiology. This is on account of the growing appreciation of the inflammatory process in the pathophysiology of atherosclerotic heart disease.

Meanwhile, being an antimetabolite, harmful to rapidly dividing cells, the danger of methotrexate to the embryo and fetus was recognized early. This made methotrexate off-limits to pregnant women, yet it also has made the drug useful as an abortifacient. Though not as good for medication abortion in unwanted but thriving pregnancies, where mifepristone/misoprostol has become the regimen of choice, methotrexate has become a workhorse in other obstetrical settings, such as for ending ectopic pregnancy.

Looking at the present and into the future, the potential for this very old medication looks wide open, as if it could go in any direction, so let’s wind up the discussion with the thought that we may be in for some surprises. Rather than jumping deeply into any rheumatologic issue, we spent most of this article weaving through other medical issues, but does this not make today’s story fairly analogous to rheumatology itself?

Dr. Warmflash is a physician from Portland, Ore. He reported no conflicts of interest.

This story was updated 2/10/2023.

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

If you could go back in time 75 years and tell Dr. Sidney Farber, the developer of methotrexate for cancer therapy, that 21st-century medicine would utilize his specially designed drug more in rheumatology than oncology, he might be surprised. He might scratch his head even more, hearing of his drug sparking interest in still other medical fields, like cardiology.

But drug repurposing is not so uncommon. One classic example is aspirin. Once the most common pain medication and used also in rheumatology, aspirin now finds a range of applications, from colorectal cancer to the prevention of cardiovascular and cerebrovascular thrombosis. Minoxidil is another example, developed for hypertension but used today mostly to stop hair loss. Perhaps most ironic is thalidomide, utilized today for leprosy and multiple myeloma, yet actually contraindicated for its original application, nausea of pregnancy.

Courtesy NIH

Methotrexate, thus, has much in common with other medical treatments, and yet its origin story is as unique and as fascinating as the story of Dr. Farber himself. While this is a rheumatology article, it’s also a story about the origin of a particular rheumatologic treatment, and so the story of that origin will take us mostly through a discussion of hematologic malignancy and of the clinical researcher who dared search for a cure.

Born in 1903, in Buffalo, New York, third of fourteen children of Jewish immigrants from Poland, Dr. Farber grew up in a household that was crowded but academically rigorous. His father, Simon, routinely brought home textbooks, assigning each child a book to read and on which to write a report. His mother, Matilda, was as devoted as her husband to raising the children to succeed in their adopted new country. Upstairs, the children were permitted to speak Yiddish, but downstairs they were required to use only English and German.

As a teen, Dr. Farber lived through the 1918 influenza pandemic that killed at least 50 million people worldwide, including more than 2,000 Buffalonians. This probably helped motivate him to study medicine, but with antisemitism overt in the America of the early 1920s, securing admission to a U.S. medical school was close to impossible. So, in what now seems like the greatest of ironies, Dr. Farber began medical studies in Germany, then transferred for the second year to a U.S. program that seemed adequate – Harvard Medical School, from which he graduated in 1927. From there, he trained as a pathologist, focusing ultimately on pediatric pathology. But, frustrated by case after case of malignancy, whose young victims he’d often have to autopsy, Dr. Farber decided that he wanted to advance the pitiful state of cancer therapeutics, especially for hematologic malignancy.

This was a tall order in the 1930s and early 1940s, when cancer therapeutics consisted only of surgical resection and very primitive forms of radiation therapy. Applicable only to neoplasia that was localized, these options were useless against malignancies in the blood, like acute lymphoblastic leukemia (ALL), but by January 1948 there was at least one glimmer of hope. At that time, one patient with ALL, 2-year-old Robert Sandler, was too ill to join his twin brother Elliott for snow play outside their home in the Dorchester section of Boston. Diagnosed back in August, Robert had suffered multiple episodes of fever, anemia, and thrombocytopenia. His illness had enlarged his spleen dramatically and caused pathologic bone fractures with excruciating bone pain, and for a while he couldn’t walk because of pressure on his lower spinal cord. All of this was the result of uncontrolled mitosis and cell division of lymphoblasts, immature lymphocytes. By December, these out-of-control cells had elevated the boy’s white blood cell count to a peak of 70,000/mcL, more than six times the high end of the normal range (4,500-11,000/mcL). This had happened despite treatment with an experimental drug, developed at Boston Children’s Hospital by Dr. Farber and his team, working on the assumption that inhibition of folate metabolism should slow the growth of tumor cells. On Dec. 28, however, Dr. Farber had switched the child to a new drug with a chemical structure just slightly different from the other agent’s.

Merely another chemical modification in a series of attempts by the research team, the new drug, aminopterin, was not expected to do anything dramatic, but Dr. Farber and the team had come such a long way since the middle of 1947, when he’d actually done the opposite of what he was doing now. On the basis of British research from India showing folic acid deficiency as the basis of a common type of anemia in malnourished people, Dr. Farber had reasoned that children with leukemia, who also suffered from anemia, might also benefit from folic acid supplementation. Even without prior rodent testing, Dr. Farber had tried giving the nutrient to patients with ALL, a strategy made possible by the presence of a spectacular chemist working on folic acid synthesis at Farber’s own hospital to help combat folate deficiency. Born into a poor Brahmin family in India, the chemist, Dr. Yellapragada SubbaRow, had begun life with so much stacked against him as to appear even less likely during childhood than the young Dr. Farber to grow up to make major contributions to medicine. Going through childhood with death all around him, Dr. SubbaRow was motivated to study medicine, but getting into medical school had been an uphill fight, given his family’s economic difficulty. Knowing that he’d also face discrimination on account of his low status after receiving admission to a medical program, SubbaRow could have made things a bit easier for himself by living within the norms of the British Imperial system, but as a supporter of Mohandas Gandhi’s nationalist movement, he boycotted British goods. As a medical student, this meant doing things like wearing Indian-made surgical gloves, instead of the English products that were expected of the students. Such actions led Dr. SubbaRow to receive a kind of second-rate medical degree, rather than the prestigious MBBS.

The political situation also led Dr. SubbaRow to emigrate to the United States, where, ironically, his medical degree initially was taken less seriously than it had been taken in his British-occupied homeland. He thus worked in the capacity of a hospital night porter at Peter Bent Brigham Hospital (the future Brigham and Women’s Hospital), doing menial tasks like changing sheets to make ends meet. He studied, however, and made enough of an impression to gain admission to the same institution that also admitted Farber through the backdoor, Harvard Medical School. This launched him into a research career in which he not only would be instrumental in developing folate antagonists and other classes of drugs, but also would make him the codiscoverer of the role of creatine phosphate and ATP in cellular energy metabolism. Sadly, even after obtaining his top-notch American credentials and contributing through his research to what you might say is a good chunk of the biochemistry pathways that first year medical students memorize without ever learning who discovered them, Dr. SubbaRow still faced prejudice for the rest of his life, which turned out to last only until the age of 53. To add insult to injury, he is rarely remembered for his role.

Dr. Farber proceeded with the folic acid supplementation idea in patients with ALL, even though ALL caused a hypoproliferative anemia, whereas anemia from folate deficiency was megaloblastic, meaning that erythrocytes were produced but they were oversized and dysfunctional. Tragically, folic acid had accelerated the disease process in children with ALL, but the process of chemical experimentation aimed at synthesizing folate also produced some compounds that mimicked chemical precursors of folate in a way that made them antifolates, inhibitors of folate metabolism. If folic acid made lymphoblasts grow faster, Dr. Farber had reasoned that antifolates should inhibit their growth. He thus asked the chemistry lab to focus on folate inhibitors. Testing aminopterin, beginning with young Robert Sandler at the end of December, is what proved his hypothesis correct. By late January, aminopterin had brought the child’s WBC count down to the realm of 12,000, just slightly above normal, with symptoms and signs abating as well, and by February, the child could play with his twin brother. It was not a cure; malignant lymphoblasts still showed on microscopy of Robert’s blood. While he and some 15 other children whom Dr. Farber treated in this early trial would all succumb to ALL, they experienced remission lasting several months.

This was a big deal because the concept of chemotherapy was based only on serendipitous observations of WBC counts dropping in soldiers exposed to nitrogen mustard gas during World War I and during an incident in World War II, yet aminopterin had been designed from the ground up. Though difficult to synthesize in quantities, there was no reason for Dr. Farber’s team not to keep tweaking the drug, and so they did. Replacing one hydrogen atom with a methyl group, they turned it into methotrexate.

Proving easier to synthesize and less toxic, methotrexate would become a workhorse for chemotherapy over the next couple of decades, but the capability of both methotrexate and aminopterin to blunt the growth of white blood cells and other cells did not go unnoticed outside the realm of oncology. As early as the 1950s, dermatologists were using aminopterin to treat psoriasis. This led to the approval of methotrexate for psoriasis in 1972.

Meanwhile, like oncology, infectious diseases, aviation medicine, and so many other areas of practice, rheumatology had gotten a major boost from research stemming from World War II. During the war, Dr. Philip Hench of the Mayo Clinic developed cortisone, which pilots used to stay alert and energetic during trans-Atlantic flights. But it turned out that cortisone had a powerful immunosuppressive effect that dramatically improved rheumatoid arthritis, leading Dr. Hench to receive the Nobel Prize in Physiology or Medicine in 1950. By the end of the 1950s, however, the significant side effects of long-term corticosteroid therapy were very clear, so over the next few decades there was a major effort to develop different treatments for RA and other rheumatologic diseases.

Top on the list of such agents was methotrexate, developed for RA in part by Dr. Michael Weinblatt of Brigham and Women’s Hospital in Boston. In the 1980s, Dr. Weinblatt published the first clinical trial showing the benefits of methotrexate for RA patients. This has since developed into a standard treatment, noticeably different from the original malignancy application in that it is a low-dose regimen. Patients taking methotrexate for RA typically receive no more than 25 mg per week orally, and often much less. Rheumatology today includes expertise in keeping long-term methotrexate therapy safe by monitoring liver function and through other routine tests. The routine nature of the therapy has brought methotrexate to the point of beckoning in a realm that Dr. Farber might not have predicted in his wildest imagination: cardiology. This is on account of the growing appreciation of the inflammatory process in the pathophysiology of atherosclerotic heart disease.

Meanwhile, being an antimetabolite, harmful to rapidly dividing cells, the danger of methotrexate to the embryo and fetus was recognized early. This made methotrexate off-limits to pregnant women, yet it also has made the drug useful as an abortifacient. Though not as good for medication abortion in unwanted but thriving pregnancies, where mifepristone/misoprostol has become the regimen of choice, methotrexate has become a workhorse in other obstetrical settings, such as for ending ectopic pregnancy.

Looking at the present and into the future, the potential for this very old medication looks wide open, as if it could go in any direction, so let’s wind up the discussion with the thought that we may be in for some surprises. Rather than jumping deeply into any rheumatologic issue, we spent most of this article weaving through other medical issues, but does this not make today’s story fairly analogous to rheumatology itself?

Dr. Warmflash is a physician from Portland, Ore. He reported no conflicts of interest.

This story was updated 2/10/2023.

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

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

As a toddler undergoing treatment at McMaster Children’s Hospital in Hamilton, Ont., Caroline Diorio, MD, couldn’t grasp what the nice doctors scurrying in and out of her room were doing. She just knew they were taking care of her.

Dr. Diorio had pediatric immune thrombocytopenia (ITP), a type of platelet disorder in which the immune system attacks blood platelets for usually unknown reasons.

“I remember very much how worried my parents were,” recalled Dr. Diorio, now a hematologist-oncologist at Children’s Hospital of Philadelphia. “And I remember how the tone of the doctor’s voice and the way the doctors communicated provided so much reassurance to my parents.”

Dr. Diorio’s ITP resolved within a few years, but her experience left a lasting impression.

“From that moment on, I don’t remember a time that I didn’t want to be a doctor,” she said. “I had these really formative experiences with doctors who were so lovely, and I thought, ‘I want to do that.’ ”

Though she considered other specialties in medical school at the University of Toronto, Dr. Diorio kept feeling drawn back to pediatric oncology and hematology.

“I have always loved the commitment that parents have to their kids and the team approach that exists,” she said. “Hematology/oncology allowed me to take care of really sick kids but also have this long-term relationship with them and their parents, which I really value and love.”

Dr. Diorio even completed her residency at McMaster alongside one of the same physicians who had cared for her as a child, Ronald Duncan Barr, MD. “It sort of all came full circle,” she said.

Today, Dr. Diorio draws inspiration from memories of her childhood experience. “I try to recreate that and provide as much kindness and compassion as I can for patients and their families, to help when people are in this incredibly vulnerable situation,” she said.

But she takes that even further by researching new therapies for patients who have run out of options, particularly those with T-cell acute lymphoblastic leukemia (T-ALL).

For B-cell ALL and several other blood cancers, an effective option is CAR T-cell therapy, in which physicians collect T-cells from the patient, re-engineer the T cells in the lab so they recognize the proteins expressed on the surface of cancerous cells – called blasts – and then introduce the modified T-cells back into the patient. Once infused, the re-engineered T-cells attack the blasts with the tell-tale proteins.

But with T-ALL, T-cells themselves are infected with cancer, so autologous CAR T-cell therapy is not currently an option, and no allogeneic CAR T-cell therapies have been approved. Dr. Diorio is part of a cutting-edge research team led by David T. Teachey, MD, striving for breakthroughs. “She’s a brilliant clinician, extremely smart and hard-working, exceptional work ethic, great interaction with patients and families with a great bedside manner,” Dr. Teachey said of Dr. Diorio. “She’s just a superstar all around.”

Dr. Teachey first piqued Dr. Diorio’s interest in researching innovative T-ALL therapies when she arrived at CHOP as a hematology/oncology fellow in 2018 and pursued a master of science degree in translational research under his tutelage at the University of Pennsylvania. Then, for a time, the COVID-19 pandemic shut down most research.

“Caroline pivoted and was at the front line, collecting samples and helping with research on SARS-CoV-2 very early in the pandemic,” Dr. Teachey said. “She was able to then pivot back, taking the skills she learned from that work in the pandemic and applying it to what she was doing in the CAR T-cell space and T-ALL.”

Extraordinary gains in pediatric cancer over the past several decades mean that more than 80% of children diagnosed with cancer today will become long-term survivors. “The 20% of the time that we don’t get the result we want is obviously devastating,” Dr. Diorio said. “However, that’s incredibly motivating to try to make better treatments.”

Her current focus is finding a way to use CAR T-cell therapy in children with T-ALL. About 85% of children with T-ALL do well with standard first-line treatments of chemotherapy, but the 15% who relapse or have chemo-refractory disease have a far lower survival rate – less than 30%, Dr. Diorio said.

The problem with autologous CAR T-cell therapy in T-ALL is twofold: It’s difficult to sort out healthy T cells from the cancerous T cells, and the target current re-engineered T-cells go after is on healthy cells, too.

“What happens is a problem called fratricide – basically the CAR T-cells are killing their brothers,” she said. So Dr. Diorio and her colleagues are trying to modify CAR T-cell strategies to target different markers. One target they’re investigating is CD7, but using CRISPR to gene-edit out CD7 from healthy cells requires making two cuts in the DNA.

“Any time you break DNA, you have to repair it, and any time you repair it, there’s a chance of making a mistake,” Dr. Diorio said. So she used a different technique, cytosine-based editing, which requires only one cut. “You put in what you want, and it’s much more precise and less error-prone.” Cytosine-based editing also preserves T cells’ vitality; too many cuts impair T-cell growth, but that doesn’t happen with cytosine-based editing. In August of 2022, Dr. Diorio published a study demonstrating this technique while the team has continued looking for other targets that show up on cancer cells but not on healthy T-cells.

“I’m not invested in one particular strategy,” Dr. Diorio said. “I’m invested in finding a strategy that works for the maximum number of patients.”

That pragmatic approach may be why Dr. Teachey describes her as an out-of-the-box thinker.

“She brings novel ideas to the table, and not everybody who’s a physician-scientist has that ability to really think about taking things in the bench to the bedside and then back again,” Dr. Teachey said. “It’s knowing what questions are important to ask for our patients and how to study those and the research base, so that you can improve treatments for kids with leukemia.”

Their research looks promising so far. Clinical trials are in development for the CD7-targeted CAR T, and they’re collaborating with others on clinical trials for CAR-T targeting another protein, CD38. In the midst of it all, Dr. Diorio remains focused on her patients.

“It’s really a privilege to see the incredible grace people have in these very difficult circumstances,” Dr. Diorio said. “I find it really motivating to try to make things easier for people, and I try to spend every day looking for better treatments so people don’t have to go through that.”

Dr. Diorio has no disclosures. Dr. Teachey has served on the advisory boards of BEAM, Jazz, Janssen, and Sobi and has received research funding from BEAM, Jazz, Servier, and Neoimmune Tech. He has multiple patents pending on CAR-T therapy.

As a toddler undergoing treatment at McMaster Children’s Hospital in Hamilton, Ont., Caroline Diorio, MD, couldn’t grasp what the nice doctors scurrying in and out of her room were doing. She just knew they were taking care of her.

Dr. Diorio had pediatric immune thrombocytopenia (ITP), a type of platelet disorder in which the immune system attacks blood platelets for usually unknown reasons.

“I remember very much how worried my parents were,” recalled Dr. Diorio, now a hematologist-oncologist at Children’s Hospital of Philadelphia. “And I remember how the tone of the doctor’s voice and the way the doctors communicated provided so much reassurance to my parents.”

Dr. Diorio’s ITP resolved within a few years, but her experience left a lasting impression.

“From that moment on, I don’t remember a time that I didn’t want to be a doctor,” she said. “I had these really formative experiences with doctors who were so lovely, and I thought, ‘I want to do that.’ ”

Though she considered other specialties in medical school at the University of Toronto, Dr. Diorio kept feeling drawn back to pediatric oncology and hematology.

“I have always loved the commitment that parents have to their kids and the team approach that exists,” she said. “Hematology/oncology allowed me to take care of really sick kids but also have this long-term relationship with them and their parents, which I really value and love.”

Dr. Diorio even completed her residency at McMaster alongside one of the same physicians who had cared for her as a child, Ronald Duncan Barr, MD. “It sort of all came full circle,” she said.

Today, Dr. Diorio draws inspiration from memories of her childhood experience. “I try to recreate that and provide as much kindness and compassion as I can for patients and their families, to help when people are in this incredibly vulnerable situation,” she said.

But she takes that even further by researching new therapies for patients who have run out of options, particularly those with T-cell acute lymphoblastic leukemia (T-ALL).

For B-cell ALL and several other blood cancers, an effective option is CAR T-cell therapy, in which physicians collect T-cells from the patient, re-engineer the T cells in the lab so they recognize the proteins expressed on the surface of cancerous cells – called blasts – and then introduce the modified T-cells back into the patient. Once infused, the re-engineered T-cells attack the blasts with the tell-tale proteins.

But with T-ALL, T-cells themselves are infected with cancer, so autologous CAR T-cell therapy is not currently an option, and no allogeneic CAR T-cell therapies have been approved. Dr. Diorio is part of a cutting-edge research team led by David T. Teachey, MD, striving for breakthroughs. “She’s a brilliant clinician, extremely smart and hard-working, exceptional work ethic, great interaction with patients and families with a great bedside manner,” Dr. Teachey said of Dr. Diorio. “She’s just a superstar all around.”

Dr. Teachey first piqued Dr. Diorio’s interest in researching innovative T-ALL therapies when she arrived at CHOP as a hematology/oncology fellow in 2018 and pursued a master of science degree in translational research under his tutelage at the University of Pennsylvania. Then, for a time, the COVID-19 pandemic shut down most research.

“Caroline pivoted and was at the front line, collecting samples and helping with research on SARS-CoV-2 very early in the pandemic,” Dr. Teachey said. “She was able to then pivot back, taking the skills she learned from that work in the pandemic and applying it to what she was doing in the CAR T-cell space and T-ALL.”

Extraordinary gains in pediatric cancer over the past several decades mean that more than 80% of children diagnosed with cancer today will become long-term survivors. “The 20% of the time that we don’t get the result we want is obviously devastating,” Dr. Diorio said. “However, that’s incredibly motivating to try to make better treatments.”

Her current focus is finding a way to use CAR T-cell therapy in children with T-ALL. About 85% of children with T-ALL do well with standard first-line treatments of chemotherapy, but the 15% who relapse or have chemo-refractory disease have a far lower survival rate – less than 30%, Dr. Diorio said.

The problem with autologous CAR T-cell therapy in T-ALL is twofold: It’s difficult to sort out healthy T cells from the cancerous T cells, and the target current re-engineered T-cells go after is on healthy cells, too.

“What happens is a problem called fratricide – basically the CAR T-cells are killing their brothers,” she said. So Dr. Diorio and her colleagues are trying to modify CAR T-cell strategies to target different markers. One target they’re investigating is CD7, but using CRISPR to gene-edit out CD7 from healthy cells requires making two cuts in the DNA.

“Any time you break DNA, you have to repair it, and any time you repair it, there’s a chance of making a mistake,” Dr. Diorio said. So she used a different technique, cytosine-based editing, which requires only one cut. “You put in what you want, and it’s much more precise and less error-prone.” Cytosine-based editing also preserves T cells’ vitality; too many cuts impair T-cell growth, but that doesn’t happen with cytosine-based editing. In August of 2022, Dr. Diorio published a study demonstrating this technique while the team has continued looking for other targets that show up on cancer cells but not on healthy T-cells.

“I’m not invested in one particular strategy,” Dr. Diorio said. “I’m invested in finding a strategy that works for the maximum number of patients.”

That pragmatic approach may be why Dr. Teachey describes her as an out-of-the-box thinker.

“She brings novel ideas to the table, and not everybody who’s a physician-scientist has that ability to really think about taking things in the bench to the bedside and then back again,” Dr. Teachey said. “It’s knowing what questions are important to ask for our patients and how to study those and the research base, so that you can improve treatments for kids with leukemia.”

Their research looks promising so far. Clinical trials are in development for the CD7-targeted CAR T, and they’re collaborating with others on clinical trials for CAR-T targeting another protein, CD38. In the midst of it all, Dr. Diorio remains focused on her patients.

“It’s really a privilege to see the incredible grace people have in these very difficult circumstances,” Dr. Diorio said. “I find it really motivating to try to make things easier for people, and I try to spend every day looking for better treatments so people don’t have to go through that.”

Dr. Diorio has no disclosures. Dr. Teachey has served on the advisory boards of BEAM, Jazz, Janssen, and Sobi and has received research funding from BEAM, Jazz, Servier, and Neoimmune Tech. He has multiple patents pending on CAR-T therapy.

As a toddler undergoing treatment at McMaster Children’s Hospital in Hamilton, Ont., Caroline Diorio, MD, couldn’t grasp what the nice doctors scurrying in and out of her room were doing. She just knew they were taking care of her.

Dr. Diorio had pediatric immune thrombocytopenia (ITP), a type of platelet disorder in which the immune system attacks blood platelets for usually unknown reasons.

“I remember very much how worried my parents were,” recalled Dr. Diorio, now a hematologist-oncologist at Children’s Hospital of Philadelphia. “And I remember how the tone of the doctor’s voice and the way the doctors communicated provided so much reassurance to my parents.”

Dr. Diorio’s ITP resolved within a few years, but her experience left a lasting impression.

“From that moment on, I don’t remember a time that I didn’t want to be a doctor,” she said. “I had these really formative experiences with doctors who were so lovely, and I thought, ‘I want to do that.’ ”

Though she considered other specialties in medical school at the University of Toronto, Dr. Diorio kept feeling drawn back to pediatric oncology and hematology.

“I have always loved the commitment that parents have to their kids and the team approach that exists,” she said. “Hematology/oncology allowed me to take care of really sick kids but also have this long-term relationship with them and their parents, which I really value and love.”

Dr. Diorio even completed her residency at McMaster alongside one of the same physicians who had cared for her as a child, Ronald Duncan Barr, MD. “It sort of all came full circle,” she said.

Today, Dr. Diorio draws inspiration from memories of her childhood experience. “I try to recreate that and provide as much kindness and compassion as I can for patients and their families, to help when people are in this incredibly vulnerable situation,” she said.

But she takes that even further by researching new therapies for patients who have run out of options, particularly those with T-cell acute lymphoblastic leukemia (T-ALL).

For B-cell ALL and several other blood cancers, an effective option is CAR T-cell therapy, in which physicians collect T-cells from the patient, re-engineer the T cells in the lab so they recognize the proteins expressed on the surface of cancerous cells – called blasts – and then introduce the modified T-cells back into the patient. Once infused, the re-engineered T-cells attack the blasts with the tell-tale proteins.

But with T-ALL, T-cells themselves are infected with cancer, so autologous CAR T-cell therapy is not currently an option, and no allogeneic CAR T-cell therapies have been approved. Dr. Diorio is part of a cutting-edge research team led by David T. Teachey, MD, striving for breakthroughs. “She’s a brilliant clinician, extremely smart and hard-working, exceptional work ethic, great interaction with patients and families with a great bedside manner,” Dr. Teachey said of Dr. Diorio. “She’s just a superstar all around.”

Dr. Teachey first piqued Dr. Diorio’s interest in researching innovative T-ALL therapies when she arrived at CHOP as a hematology/oncology fellow in 2018 and pursued a master of science degree in translational research under his tutelage at the University of Pennsylvania. Then, for a time, the COVID-19 pandemic shut down most research.

“Caroline pivoted and was at the front line, collecting samples and helping with research on SARS-CoV-2 very early in the pandemic,” Dr. Teachey said. “She was able to then pivot back, taking the skills she learned from that work in the pandemic and applying it to what she was doing in the CAR T-cell space and T-ALL.”

Extraordinary gains in pediatric cancer over the past several decades mean that more than 80% of children diagnosed with cancer today will become long-term survivors. “The 20% of the time that we don’t get the result we want is obviously devastating,” Dr. Diorio said. “However, that’s incredibly motivating to try to make better treatments.”

Her current focus is finding a way to use CAR T-cell therapy in children with T-ALL. About 85% of children with T-ALL do well with standard first-line treatments of chemotherapy, but the 15% who relapse or have chemo-refractory disease have a far lower survival rate – less than 30%, Dr. Diorio said.

The problem with autologous CAR T-cell therapy in T-ALL is twofold: It’s difficult to sort out healthy T cells from the cancerous T cells, and the target current re-engineered T-cells go after is on healthy cells, too.

“What happens is a problem called fratricide – basically the CAR T-cells are killing their brothers,” she said. So Dr. Diorio and her colleagues are trying to modify CAR T-cell strategies to target different markers. One target they’re investigating is CD7, but using CRISPR to gene-edit out CD7 from healthy cells requires making two cuts in the DNA.

“Any time you break DNA, you have to repair it, and any time you repair it, there’s a chance of making a mistake,” Dr. Diorio said. So she used a different technique, cytosine-based editing, which requires only one cut. “You put in what you want, and it’s much more precise and less error-prone.” Cytosine-based editing also preserves T cells’ vitality; too many cuts impair T-cell growth, but that doesn’t happen with cytosine-based editing. In August of 2022, Dr. Diorio published a study demonstrating this technique while the team has continued looking for other targets that show up on cancer cells but not on healthy T-cells.

“I’m not invested in one particular strategy,” Dr. Diorio said. “I’m invested in finding a strategy that works for the maximum number of patients.”

That pragmatic approach may be why Dr. Teachey describes her as an out-of-the-box thinker.

“She brings novel ideas to the table, and not everybody who’s a physician-scientist has that ability to really think about taking things in the bench to the bedside and then back again,” Dr. Teachey said. “It’s knowing what questions are important to ask for our patients and how to study those and the research base, so that you can improve treatments for kids with leukemia.”

Their research looks promising so far. Clinical trials are in development for the CD7-targeted CAR T, and they’re collaborating with others on clinical trials for CAR-T targeting another protein, CD38. In the midst of it all, Dr. Diorio remains focused on her patients.

“It’s really a privilege to see the incredible grace people have in these very difficult circumstances,” Dr. Diorio said. “I find it really motivating to try to make things easier for people, and I try to spend every day looking for better treatments so people don’t have to go through that.”

Dr. Diorio has no disclosures. Dr. Teachey has served on the advisory boards of BEAM, Jazz, Janssen, and Sobi and has received research funding from BEAM, Jazz, Servier, and Neoimmune Tech. He has multiple patents pending on CAR-T therapy.