AVAHO

A deep learning artificial intelligence (AI) model that used only a single histopathological slide predicted the risk of distant recurrence among endometrial cancer patients in a new study.

Endometrial cancer is the most frequently occurring uterine cancer. Early-stage patients have about a 95% 5-year survival, but distant recurrence is associated with very poor survival, according to Sarah Fremond, MSc, an author of the research (Abstract 5695), which she presented at the annual meeting of the American Association for Cancer Research.

“Most patients with endometrial cancer have a good prognosis and would not require any adjuvant treatment, but there is a proportion that will develop distant recurrence. For those you want to recommend adjuvant chemotherapy, because currently in the adjuvant setting, that’s the only treatment that is known to lower the risk of distant recurrence. But that also causes morbidity. Therefore, our clinical question was how to accurately identify patients at low and high risk of distant recurrence to reduce under- and overtreatment,” said Ms. Fremond, a PhD candidate at Leiden (the Netherlands) University Medical Center.

Pathologists can attempt such predictions, but Ms. Fremond noted that there are challenges. “There is a lot of variability between pathologists, and we don’t even use the entire visual information present in the H&E [hematoxylin and eosin] tumor slide. When it comes to molecular testing, it is hampered by cost, turnaround time, and sometimes interpretation. It’s quite complex to combine those data to specifically target risk of distant recurrence for patients with endometrial cancer.”

In her presentation, Ms. Fremond described how she and her colleagues used digitized histopathological slides in their research. She and her coauthors developed the AI model as part of a collaboration that included the AIRMEC Consortium, Leiden University Medical Center, the TransPORTEC Consortium, and the University of Zürich.

The researchers used long-term follow-up data from 1,408 patients drawn from three clinical cohorts and participants in the PORTEC-1, PORTEC-2, and PORTEC-3 studies, which tested radiotherapy and adjuvant therapy outcomes in endometrial cancer. Patients who had received prior adjuvant chemotherapy were excluded. In the model development phase, the system analyzed a single representative histopathological slide image from each patient and compared it with the known time to distant recurrence to identify patterns.

Once the system had been trained, the researchers applied it to a novel group of 353 patients. It ranked 89 patients as having a low risk of recurrence, 175 at intermediate risk, and 89 at high risk of recurrence. The system performed well: 3.37% of low-risk patients experienced a distant recurrence, as did 15.43% of the intermediate-risk group and 36% of the high-risk group.

The researchers also employed an external validation group with 152 patients and three slides per patient, with a 2.8-year follow-up. The model performed with a C index of 0.805 (±0.0136) when a random slide was selected for each patient, and the median predicted risk score per patient was associated with differences in distant recurrence-free survival between the three risk groups with a C index of 0.816 (P < .0001).
 

Questions about research and their answers

Session moderator Kristin Swanson, PhD, asked if the AI could be used with the pathology slide’s visible features to learn more about the underlying biology and pathophysiology of tumors.

“Overlying the HECTOR on to the tissue seems like a logical opportunity to go and then explore the biology and what’s attributed as a high-risk region,” said Dr. Swanson, who is director of the Mathematical NeuroOncology Lab and codirector of the Precision NeuroTherapeutics Innovation Program at Mayo Clinic Arizona, Phoenix.

Ms. Fremond agreed that the AI has the potential to be used that way.”

During the Q&A, an audience member asked how likely the model is to perform in populations that differ significantly from the populations used in her study.

Ms. Fremond responded that the populations used to develop and test the models were in or close to the Netherlands, and little information was available regarding patient ethnicity. “There is a possibility that perhaps we would have a different performance on a population that includes more minorities. That needs to be checked,” said Ms. Fremond.

The study is limited by its retrospective nature.

Ms. Fremond and Dr. Swanson have no relevant financial disclosures.

A deep learning artificial intelligence (AI) model that used only a single histopathological slide predicted the risk of distant recurrence among endometrial cancer patients in a new study.

Endometrial cancer is the most frequently occurring uterine cancer. Early-stage patients have about a 95% 5-year survival, but distant recurrence is associated with very poor survival, according to Sarah Fremond, MSc, an author of the research (Abstract 5695), which she presented at the annual meeting of the American Association for Cancer Research.

“Most patients with endometrial cancer have a good prognosis and would not require any adjuvant treatment, but there is a proportion that will develop distant recurrence. For those you want to recommend adjuvant chemotherapy, because currently in the adjuvant setting, that’s the only treatment that is known to lower the risk of distant recurrence. But that also causes morbidity. Therefore, our clinical question was how to accurately identify patients at low and high risk of distant recurrence to reduce under- and overtreatment,” said Ms. Fremond, a PhD candidate at Leiden (the Netherlands) University Medical Center.

Pathologists can attempt such predictions, but Ms. Fremond noted that there are challenges. “There is a lot of variability between pathologists, and we don’t even use the entire visual information present in the H&E [hematoxylin and eosin] tumor slide. When it comes to molecular testing, it is hampered by cost, turnaround time, and sometimes interpretation. It’s quite complex to combine those data to specifically target risk of distant recurrence for patients with endometrial cancer.”

In her presentation, Ms. Fremond described how she and her colleagues used digitized histopathological slides in their research. She and her coauthors developed the AI model as part of a collaboration that included the AIRMEC Consortium, Leiden University Medical Center, the TransPORTEC Consortium, and the University of Zürich.

The researchers used long-term follow-up data from 1,408 patients drawn from three clinical cohorts and participants in the PORTEC-1, PORTEC-2, and PORTEC-3 studies, which tested radiotherapy and adjuvant therapy outcomes in endometrial cancer. Patients who had received prior adjuvant chemotherapy were excluded. In the model development phase, the system analyzed a single representative histopathological slide image from each patient and compared it with the known time to distant recurrence to identify patterns.

Once the system had been trained, the researchers applied it to a novel group of 353 patients. It ranked 89 patients as having a low risk of recurrence, 175 at intermediate risk, and 89 at high risk of recurrence. The system performed well: 3.37% of low-risk patients experienced a distant recurrence, as did 15.43% of the intermediate-risk group and 36% of the high-risk group.

The researchers also employed an external validation group with 152 patients and three slides per patient, with a 2.8-year follow-up. The model performed with a C index of 0.805 (±0.0136) when a random slide was selected for each patient, and the median predicted risk score per patient was associated with differences in distant recurrence-free survival between the three risk groups with a C index of 0.816 (P < .0001).
 

Questions about research and their answers

Session moderator Kristin Swanson, PhD, asked if the AI could be used with the pathology slide’s visible features to learn more about the underlying biology and pathophysiology of tumors.

“Overlying the HECTOR on to the tissue seems like a logical opportunity to go and then explore the biology and what’s attributed as a high-risk region,” said Dr. Swanson, who is director of the Mathematical NeuroOncology Lab and codirector of the Precision NeuroTherapeutics Innovation Program at Mayo Clinic Arizona, Phoenix.

Ms. Fremond agreed that the AI has the potential to be used that way.”

During the Q&A, an audience member asked how likely the model is to perform in populations that differ significantly from the populations used in her study.

Ms. Fremond responded that the populations used to develop and test the models were in or close to the Netherlands, and little information was available regarding patient ethnicity. “There is a possibility that perhaps we would have a different performance on a population that includes more minorities. That needs to be checked,” said Ms. Fremond.

The study is limited by its retrospective nature.

Ms. Fremond and Dr. Swanson have no relevant financial disclosures.

A deep learning artificial intelligence (AI) model that used only a single histopathological slide predicted the risk of distant recurrence among endometrial cancer patients in a new study.

Endometrial cancer is the most frequently occurring uterine cancer. Early-stage patients have about a 95% 5-year survival, but distant recurrence is associated with very poor survival, according to Sarah Fremond, MSc, an author of the research (Abstract 5695), which she presented at the annual meeting of the American Association for Cancer Research.

“Most patients with endometrial cancer have a good prognosis and would not require any adjuvant treatment, but there is a proportion that will develop distant recurrence. For those you want to recommend adjuvant chemotherapy, because currently in the adjuvant setting, that’s the only treatment that is known to lower the risk of distant recurrence. But that also causes morbidity. Therefore, our clinical question was how to accurately identify patients at low and high risk of distant recurrence to reduce under- and overtreatment,” said Ms. Fremond, a PhD candidate at Leiden (the Netherlands) University Medical Center.

Pathologists can attempt such predictions, but Ms. Fremond noted that there are challenges. “There is a lot of variability between pathologists, and we don’t even use the entire visual information present in the H&E [hematoxylin and eosin] tumor slide. When it comes to molecular testing, it is hampered by cost, turnaround time, and sometimes interpretation. It’s quite complex to combine those data to specifically target risk of distant recurrence for patients with endometrial cancer.”

In her presentation, Ms. Fremond described how she and her colleagues used digitized histopathological slides in their research. She and her coauthors developed the AI model as part of a collaboration that included the AIRMEC Consortium, Leiden University Medical Center, the TransPORTEC Consortium, and the University of Zürich.

The researchers used long-term follow-up data from 1,408 patients drawn from three clinical cohorts and participants in the PORTEC-1, PORTEC-2, and PORTEC-3 studies, which tested radiotherapy and adjuvant therapy outcomes in endometrial cancer. Patients who had received prior adjuvant chemotherapy were excluded. In the model development phase, the system analyzed a single representative histopathological slide image from each patient and compared it with the known time to distant recurrence to identify patterns.

Once the system had been trained, the researchers applied it to a novel group of 353 patients. It ranked 89 patients as having a low risk of recurrence, 175 at intermediate risk, and 89 at high risk of recurrence. The system performed well: 3.37% of low-risk patients experienced a distant recurrence, as did 15.43% of the intermediate-risk group and 36% of the high-risk group.

The researchers also employed an external validation group with 152 patients and three slides per patient, with a 2.8-year follow-up. The model performed with a C index of 0.805 (±0.0136) when a random slide was selected for each patient, and the median predicted risk score per patient was associated with differences in distant recurrence-free survival between the three risk groups with a C index of 0.816 (P < .0001).
 

Questions about research and their answers

Session moderator Kristin Swanson, PhD, asked if the AI could be used with the pathology slide’s visible features to learn more about the underlying biology and pathophysiology of tumors.

“Overlying the HECTOR on to the tissue seems like a logical opportunity to go and then explore the biology and what’s attributed as a high-risk region,” said Dr. Swanson, who is director of the Mathematical NeuroOncology Lab and codirector of the Precision NeuroTherapeutics Innovation Program at Mayo Clinic Arizona, Phoenix.

Ms. Fremond agreed that the AI has the potential to be used that way.”

During the Q&A, an audience member asked how likely the model is to perform in populations that differ significantly from the populations used in her study.

Ms. Fremond responded that the populations used to develop and test the models were in or close to the Netherlands, and little information was available regarding patient ethnicity. “There is a possibility that perhaps we would have a different performance on a population that includes more minorities. That needs to be checked,” said Ms. Fremond.

The study is limited by its retrospective nature.

Ms. Fremond and Dr. Swanson have no relevant financial disclosures.

Tarek Mouhieddine, MD, grew up as a child of war-torn Lebanon. Now building his career as a New York–based hematologist oncologist, Dr. Mouhieddine works in the trenches of a very different kind of battle. His mission: Find a way to reverse multiple myeloma in its mysterious early “smoldering” stages and give patients a new lease on life before the cancer takes hold.

“If we start treatment earlier, in the smoldering phase, maybe there is a chance of actually curing the disease and completely getting rid of it,” said Dr. Mouhieddine, 31, a research fellow at the Icahn School of Medicine at Mount Sinai, in New York. “We haven’t proven that yet, and it’s going to take years before we’re able to prove it. I’m hoping to be one of those spearheading the initiative.”

Dr. Tarek Mouhieddine

As he develops clinical trials, the young physician scientist has another focus: A deeply personal connection to the very disease he’s trying to cure. Last year Dr. Mouhieddine diagnosed his aunt back in Lebanon with multiple myeloma. “I have always been close to her, and I’m like her son,” he said, and her situation is especially scary because she lives in a country where treatment options are limited.

Dr. Mouhieddine was born and raised in Beirut, the son of a sports journalist father and a mother who worked in a bank. Lebanon’s civil war ended in 1990, shortly before his birth, but political instability returned when he was a child.

“Everything was a disaster,” he recalled. “There was a period of time when there were bombs throughout the city because certain politicians were being targeted. I remember when groups of people would have gunfights in the street.”

Dr. Mouhieddine attended the American University of Beirut, then after college and medical school there, he headed to the United States.

“I wanted to make a difference in medicine. And I knew that if I stayed back home, I wouldn’t be able to,” he said. Fortunately, “everybody has made me feel that I really belong here, and I’ve never felt like I’m an outsider.”

Early on, as he went through fellowships and residency, he developed an interest in multiple myeloma.

Ajai Chari, MD, a colleague of Dr. Mouhieddine’s at Icahn School of Medicine, said in an interview, “I remember meeting him at a conference before he had even started an internal medicine residency, let alone a hematology oncology fellowship. He was already certain he wanted to work in multiple myeloma, due to his work at Dana-Farber Cancer Institute.”

Myeloma was especially intriguing to Dr. Mouhieddine because of the rapid rate of progress in treating the disease. “Over the past 10 years, the myeloma field has advanced at such an extremely fast pace, more than any other cancer,” he said. “Maybe 15 years ago, you would tell someone with newly diagnosed myeloma that they had a chance for an average of another 2 years. Now, we tell patients they have 10 years to live on average, which means you could live 15 or 20 years. That alone was astounding to me and piqued my interest in myeloma.”

At the same time, smoldering myeloma – which can be discovered during routine blood work – remains little understood. As the National Cancer Institute explains, “smoldering myeloma is a precancerous condition that alters certain proteins in blood and/or increases plasma cells in bone marrow, but it does not cause symptoms of disease. About half of those diagnosed with the condition, however, will develop multiple myeloma within 5 years.”

“If we understand what drives smoldering myeloma, we may be able to prevent it from progressing to its active form,” said hematologist oncologist Samir Parekh, MD, who works with Dr. Mouhieddine at Icahn School of Medicine. “Or at the minimum, we could better predict who will progress so we can tailor therapy for high-risk patients and minimize toxicity by not overtreating patients who may not need therapy.”

Dr. Mouhieddine’s current work is focusing on developing clinical trials to test whether immunotherapy can snuff out myeloma when it’s at the smoldering stage, “before anything bad happens.

“If a myeloma patient comes in with renal failure, and we treat the myeloma at that stage, it doesn’t mean that the patient’s kidneys are gonna go back to normal. A lot of the damage can be permanent,” he said. “Even when you treat multiple myeloma, and it goes into remission, it ends up coming back. And you just have to go from one therapy to the other.”

In contrast, a successful treatment for smoldering myeloma would prevent progression to the full disease. In other words, it would be a cure – which is now elusive.

Specifically, Dr. Mouhieddine hopes to test whether bispecific antibodies, a type of immunotherapy that enlists the body’s T cells to kill myeloma cells, will be effective in the smoldering phase. Bispecific antibodies are now being explored as treatments for full multiple myeloma when the immune system is weaker, he said, and they may be even more effective earlier, when the body is better equipped to fight off the disease.

Dr. Mouhieddine hopes better treatments for multiple myeloma itself will help save his 64-year-old aunt Hassana, back in Beirut. He diagnosed her in 2022 after she told him that she felt tired all the time and underwent various tests. The woman he calls his “second mom” is doing well, despite struggles to buy medication due to the lack of access to bank funds in Lebanon.

Dr. Tarek Mouhieddine

Tarek Mouhieddine, MD, grew up as a child of war-torn Lebanon. Now building his career as a New York–based hematologist oncologist, Dr. Mouhieddine works in the trenches of a very different kind of battle. His mission: Find a way to reverse multiple myeloma in its mysterious early “smoldering” stages and give patients a new lease on life before the cancer takes hold.

“If we start treatment earlier, in the smoldering phase, maybe there is a chance of actually curing the disease and completely getting rid of it,” said Dr. Mouhieddine, 31, a research fellow at the Icahn School of Medicine at Mount Sinai, in New York. “We haven’t proven that yet, and it’s going to take years before we’re able to prove it. I’m hoping to be one of those spearheading the initiative.”

Dr. Tarek Mouhieddine

As he develops clinical trials, the young physician scientist has another focus: A deeply personal connection to the very disease he’s trying to cure. Last year Dr. Mouhieddine diagnosed his aunt back in Lebanon with multiple myeloma. “I have always been close to her, and I’m like her son,” he said, and her situation is especially scary because she lives in a country where treatment options are limited.

Dr. Mouhieddine was born and raised in Beirut, the son of a sports journalist father and a mother who worked in a bank. Lebanon’s civil war ended in 1990, shortly before his birth, but political instability returned when he was a child.

“Everything was a disaster,” he recalled. “There was a period of time when there were bombs throughout the city because certain politicians were being targeted. I remember when groups of people would have gunfights in the street.”

Dr. Mouhieddine attended the American University of Beirut, then after college and medical school there, he headed to the United States.

“I wanted to make a difference in medicine. And I knew that if I stayed back home, I wouldn’t be able to,” he said. Fortunately, “everybody has made me feel that I really belong here, and I’ve never felt like I’m an outsider.”

Early on, as he went through fellowships and residency, he developed an interest in multiple myeloma.

Ajai Chari, MD, a colleague of Dr. Mouhieddine’s at Icahn School of Medicine, said in an interview, “I remember meeting him at a conference before he had even started an internal medicine residency, let alone a hematology oncology fellowship. He was already certain he wanted to work in multiple myeloma, due to his work at Dana-Farber Cancer Institute.”

Myeloma was especially intriguing to Dr. Mouhieddine because of the rapid rate of progress in treating the disease. “Over the past 10 years, the myeloma field has advanced at such an extremely fast pace, more than any other cancer,” he said. “Maybe 15 years ago, you would tell someone with newly diagnosed myeloma that they had a chance for an average of another 2 years. Now, we tell patients they have 10 years to live on average, which means you could live 15 or 20 years. That alone was astounding to me and piqued my interest in myeloma.”

At the same time, smoldering myeloma – which can be discovered during routine blood work – remains little understood. As the National Cancer Institute explains, “smoldering myeloma is a precancerous condition that alters certain proteins in blood and/or increases plasma cells in bone marrow, but it does not cause symptoms of disease. About half of those diagnosed with the condition, however, will develop multiple myeloma within 5 years.”

“If we understand what drives smoldering myeloma, we may be able to prevent it from progressing to its active form,” said hematologist oncologist Samir Parekh, MD, who works with Dr. Mouhieddine at Icahn School of Medicine. “Or at the minimum, we could better predict who will progress so we can tailor therapy for high-risk patients and minimize toxicity by not overtreating patients who may not need therapy.”

Dr. Mouhieddine’s current work is focusing on developing clinical trials to test whether immunotherapy can snuff out myeloma when it’s at the smoldering stage, “before anything bad happens.

“If a myeloma patient comes in with renal failure, and we treat the myeloma at that stage, it doesn’t mean that the patient’s kidneys are gonna go back to normal. A lot of the damage can be permanent,” he said. “Even when you treat multiple myeloma, and it goes into remission, it ends up coming back. And you just have to go from one therapy to the other.”

In contrast, a successful treatment for smoldering myeloma would prevent progression to the full disease. In other words, it would be a cure – which is now elusive.

Specifically, Dr. Mouhieddine hopes to test whether bispecific antibodies, a type of immunotherapy that enlists the body’s T cells to kill myeloma cells, will be effective in the smoldering phase. Bispecific antibodies are now being explored as treatments for full multiple myeloma when the immune system is weaker, he said, and they may be even more effective earlier, when the body is better equipped to fight off the disease.

Dr. Mouhieddine hopes better treatments for multiple myeloma itself will help save his 64-year-old aunt Hassana, back in Beirut. He diagnosed her in 2022 after she told him that she felt tired all the time and underwent various tests. The woman he calls his “second mom” is doing well, despite struggles to buy medication due to the lack of access to bank funds in Lebanon.

Dr. Tarek Mouhieddine

Tarek Mouhieddine, MD, grew up as a child of war-torn Lebanon. Now building his career as a New York–based hematologist oncologist, Dr. Mouhieddine works in the trenches of a very different kind of battle. His mission: Find a way to reverse multiple myeloma in its mysterious early “smoldering” stages and give patients a new lease on life before the cancer takes hold.

“If we start treatment earlier, in the smoldering phase, maybe there is a chance of actually curing the disease and completely getting rid of it,” said Dr. Mouhieddine, 31, a research fellow at the Icahn School of Medicine at Mount Sinai, in New York. “We haven’t proven that yet, and it’s going to take years before we’re able to prove it. I’m hoping to be one of those spearheading the initiative.”

Dr. Tarek Mouhieddine

As he develops clinical trials, the young physician scientist has another focus: A deeply personal connection to the very disease he’s trying to cure. Last year Dr. Mouhieddine diagnosed his aunt back in Lebanon with multiple myeloma. “I have always been close to her, and I’m like her son,” he said, and her situation is especially scary because she lives in a country where treatment options are limited.

Dr. Mouhieddine was born and raised in Beirut, the son of a sports journalist father and a mother who worked in a bank. Lebanon’s civil war ended in 1990, shortly before his birth, but political instability returned when he was a child.

“Everything was a disaster,” he recalled. “There was a period of time when there were bombs throughout the city because certain politicians were being targeted. I remember when groups of people would have gunfights in the street.”

Dr. Mouhieddine attended the American University of Beirut, then after college and medical school there, he headed to the United States.

“I wanted to make a difference in medicine. And I knew that if I stayed back home, I wouldn’t be able to,” he said. Fortunately, “everybody has made me feel that I really belong here, and I’ve never felt like I’m an outsider.”

Early on, as he went through fellowships and residency, he developed an interest in multiple myeloma.

Ajai Chari, MD, a colleague of Dr. Mouhieddine’s at Icahn School of Medicine, said in an interview, “I remember meeting him at a conference before he had even started an internal medicine residency, let alone a hematology oncology fellowship. He was already certain he wanted to work in multiple myeloma, due to his work at Dana-Farber Cancer Institute.”

Myeloma was especially intriguing to Dr. Mouhieddine because of the rapid rate of progress in treating the disease. “Over the past 10 years, the myeloma field has advanced at such an extremely fast pace, more than any other cancer,” he said. “Maybe 15 years ago, you would tell someone with newly diagnosed myeloma that they had a chance for an average of another 2 years. Now, we tell patients they have 10 years to live on average, which means you could live 15 or 20 years. That alone was astounding to me and piqued my interest in myeloma.”

At the same time, smoldering myeloma – which can be discovered during routine blood work – remains little understood. As the National Cancer Institute explains, “smoldering myeloma is a precancerous condition that alters certain proteins in blood and/or increases plasma cells in bone marrow, but it does not cause symptoms of disease. About half of those diagnosed with the condition, however, will develop multiple myeloma within 5 years.”

“If we understand what drives smoldering myeloma, we may be able to prevent it from progressing to its active form,” said hematologist oncologist Samir Parekh, MD, who works with Dr. Mouhieddine at Icahn School of Medicine. “Or at the minimum, we could better predict who will progress so we can tailor therapy for high-risk patients and minimize toxicity by not overtreating patients who may not need therapy.”

Dr. Mouhieddine’s current work is focusing on developing clinical trials to test whether immunotherapy can snuff out myeloma when it’s at the smoldering stage, “before anything bad happens.

“If a myeloma patient comes in with renal failure, and we treat the myeloma at that stage, it doesn’t mean that the patient’s kidneys are gonna go back to normal. A lot of the damage can be permanent,” he said. “Even when you treat multiple myeloma, and it goes into remission, it ends up coming back. And you just have to go from one therapy to the other.”

In contrast, a successful treatment for smoldering myeloma would prevent progression to the full disease. In other words, it would be a cure – which is now elusive.

Specifically, Dr. Mouhieddine hopes to test whether bispecific antibodies, a type of immunotherapy that enlists the body’s T cells to kill myeloma cells, will be effective in the smoldering phase. Bispecific antibodies are now being explored as treatments for full multiple myeloma when the immune system is weaker, he said, and they may be even more effective earlier, when the body is better equipped to fight off the disease.

Dr. Mouhieddine hopes better treatments for multiple myeloma itself will help save his 64-year-old aunt Hassana, back in Beirut. He diagnosed her in 2022 after she told him that she felt tired all the time and underwent various tests. The woman he calls his “second mom” is doing well, despite struggles to buy medication due to the lack of access to bank funds in Lebanon.

Dr. Tarek Mouhieddine

Combination treatment with the poly ADP-ribose polymerase inhibitor, olaparib, and the novel ataxia telangiectasia–mutated Rad3-related (ATR) inhibitor, ceralasertib, was well tolerated and showed some promise in pediatric patients with tumors with DNA replication stress or DNA repair deficiencies, in a new study.

The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.

The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.

In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.

In adults, poly ADP-ribose polymerase (PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.

Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.

The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.

Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.

There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.

An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.

Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.

“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.

She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.

“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.

The study is limited by its small sample size and the fact that it was not randomized.

The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.

Combination treatment with the poly ADP-ribose polymerase inhibitor, olaparib, and the novel ataxia telangiectasia–mutated Rad3-related (ATR) inhibitor, ceralasertib, was well tolerated and showed some promise in pediatric patients with tumors with DNA replication stress or DNA repair deficiencies, in a new study.

The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.

The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.

In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.

In adults, poly ADP-ribose polymerase (PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.

Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.

The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.

Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.

There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.

An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.

Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.

“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.

She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.

“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.

The study is limited by its small sample size and the fact that it was not randomized.

The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.

Combination treatment with the poly ADP-ribose polymerase inhibitor, olaparib, and the novel ataxia telangiectasia–mutated Rad3-related (ATR) inhibitor, ceralasertib, was well tolerated and showed some promise in pediatric patients with tumors with DNA replication stress or DNA repair deficiencies, in a new study.

The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.

The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.

In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.

In adults, poly ADP-ribose polymerase (PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.

Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.

The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.

Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.

There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.

An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.

Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.

“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.

She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.

“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.

The study is limited by its small sample size and the fact that it was not randomized.

The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

NEW YORK – Most patients with chronic lymphocytic leukemia (CLL) who relapse after treatment with a single agent Bruton’s tyrosine kinase (BTK) inhibitor have one of several high-risk characteristics, including complex karyotype, 17p-chromosome deletion, or a TP53 mutation. In contrast, genomically stable patients have a 4-year progression-free survival (PFS) rate of about 98% on single agent Bruton’s tyrosine kinase inhibitor therapy.

Dr. Furman

“In people who are genomically unstable, almost half will have their CLL progress on single agent BTK inhibitor therapy. These patients, I’d like to treat with combination of a Bruton’s tyrosine kinase inhibitor plus venetoclax,” said Richard R. Furman, MD, Morton Coleman MD Distinguished Professor of medicine at Weill Cornell Medicine/New York Presbyterian Hospital. He presented on treating relapsed CLL at the Great Debates and Updates Hematologic Malignancies Conference in New York, April 13-15.

The efficacy of venetoclax (VX) in treating high risk CLL patients was demonstrated in the 2019 CLL14 trial (NCT02242942) in which the main entry criteria were being treatment-naive and being considered “unfit” for treatment, meaning that a patient’s Cumulative Illness Rating Scale score was >6, or they presented with decreased kidney function. Study participants were treated with six cycles of either venetoclax-obinutuzumab (VO) or chlorambucil-obinutuzumab (CO); the 4-year PFS was 74% vs. 35.4% (P < .0001) respectively. After 12 cycles of treatment, the 74% of patients in the VO group achieved undetectable minimal residual disease rate (MRD) vs. 32% in the CO group.

Achievement of MRD did predict for outcome, but Dr. Furman concluded that while MRD is a powerful prognostic tool, it is not clinically useful given the inability of its results to guide therapy. He went on to emphasize that “of those patients who achieved MRD levels of 10-4 after 12 cycles of venetoclax, 50% had worsening and 50% had improvement of the residual disease, suggesting that we do not know the optimal duration of venetoclax treatment, as half of the patients still continue to derive benefit.”

Dr. Furman noted that ibrutinib (IB) and the second-generation drugs zanubrutinib (ZB) and acalabrutinib (AL) are all effective, but that the second-generation Bruton’s tyrosine kinase inhibitors enable patients to derive the benefit of remaining on treatment longer, because the rate of concerning cardiac complications is lower than with IB.

The ALPINE trial (NCT03734016) confirmed ZB’s significantly improved overall response rate at 78.3% vs. IB’s 62.5%, as well as a lower rate of atrial fibrillation (2.5%) vs. IB (10.1%).

Noninferiority of AL vs. IB in high-risk relapsed CLL patients was demonstrated in the ELEVATE-RR trial (NCT02477696) with both drugs having a median PFS of 38.4 months. With a median follow up of 41 months, AL demonstrated less atrial fibrillation/atrial flutter, compared with IB (9.4% vs. 16.0%) with no difference in grade > 3 infections. Furthermore, AL’s half-life being shorter than that of IB means that side effects are shorter lived.

“That’s the advantage of the second generation of Bruton’s tyrosine kinase inhibitors,” said Stefan Glück, MD, PhD, a hematologic oncologist and independent consultant who was formerly affiliated with the Sylvester Comprehensive Cancer Center and taught at the Miller School of Medicine at the University of Miami.

Dr. Glück added that “acalabrutinib and zanubrutinib have demonstrated strong efficacy and safety. When patients no longer respond to these drugs, the addition of VX is crucial. It has a completely different mechanism of action and can reverse resistance to Bruton’s tyrosine kinase inhibitors, allowing them to start working again.”

Dr. Furman also discussed proteolysis-targeting chimeras (PROTACs), one area that he expects to make a significant impact as a future therapy for CLL and many other malignancies. Despite the fact these agents are in phase I studies, he commented that “they appear, thus far, to have tremendous potential.”

Dr. Furman disclosed relationships with Abbvie, Acerta/AstraZeneca, Beigene, Jansen, TG Therapeutics, Genentech-Roche, Incyte Corporation, Loxo Oncology, MEI Pharma, Morphosys, Pharmacyclics, Sanofi/Genzyme, and X4 Pharmaceuticals. Dr. Glück reported no conflicts of interest.
 

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

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

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

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

Vaccines for the world’s most deadly diseases, like cancer and heart disease, will likely be ready by 2030 and could save millions of lives, according to the top doctor at one of the world’s leading drug companies.

The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.

“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”

The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.

The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.

Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.

“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said. 

The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.

In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.

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

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

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

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

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

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

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