Leukemia, Myelodysplasia, Transplantation

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

COVID-19 has thrown a wrench in standard treatment protocols for patients with chronic lymphocytic leukemia (CLL). These patients already face a greater risk of dying from infections, and recent research suggests they tend to have risk factors that increase their likelihood of complications and death from COVID-19.

In August, a group of oncologists from the United States and Europe published a literature-informed expert opinion to help their colleagues navigate this new CLL treatment landscape. It offers a roadmap for balancing patients’ therapeutic needs against their risk for viral infection and outlines the safest course of action for patients who test positive for COVID-19.

Mazyar Shadman, MD, MPH, an associate professor in the Clinical Research Division of the Fred Hutchinson Cancer Research Center and the Division of Medical Oncology at the University of Washington School of Medicine, in Seattle, Washington, was contacted for comment to break down what clinicians need to know about treating CLL during the pandemic. This interview has been edited for length and clarity.
 

Question: What prompted you and colleagues from the United States and Europe to write these recommendations?

Dr. Shadman: When we began the collaboration earlier this year, our colleagues in Italy and the rest of Europe had more experience with COVID-19, so they led the effort. We wanted to help oncologists manage their patients with CLL during the pandemic based on the evidence we had at the time and the unknowns we faced.
 

What’s an example of how the available evidence informed your recommendations?

At the time, we didn’t know whether patients with CLL were more likely to get COVID-19, compared to the general population, but we did have evidence already that cancer increases patients’ risk of bad outcomes and death from COVID-19. CLL, for example, can increase risk factors for infection, including hypogammaglobulinemia, innate immune dysfunction, and neutropenia, which may be exacerbated by anticancer treatments. Patients’ existing immune suppression might prevent or delay their ability to react to or cope with the virus. And many patients with CLL have other conditions that increase their risk of a severe response to COVID-19, including older age (70% of CLL patients are older than 65 years), hypertension (21%), and diabetes (26%).

These factors informed our recommendations to limit patients’ exposure to COVID-19 by reducing or postponing the number of in-person visits and routine in-hospital follow-ups, especially if they could be substituted with virtual check-ins.
 

The expert opinion recommendations are divided into three main categories: patients who are newly diagnosed with CLL but have not begun receiving therapy, those already receiving therapy but are free of COVID-19, and those who test positive for COVID-19. Let’s start with the first category. What do the recommendations say about waiting versus proceeding for newly diagnosed patients?

Our priority was balancing the negative impacts of getting COVID-19 with the negative impacts of postponing cancer treatment. We suggested taking each new CLL case on a patient-by-patient basis to determine who needed treatment tomorrow and who could wait a few weeks or months. Fortunately, CLL rarely requires immediate therapy, so the preference was to postpone treatment a few weeks, depending on the local COVID-19 outbreak situation.

In my practice, for instance, we tried to postpone visits as much as we could. Before the pandemic, patients with CLL in the watch-and-wait phase – those diagnosed but who don’t require treatment immediately – would come in for bloodwork and exams every 3-6 months. But when the pandemic hit, we skipped 3-month visits for patients with stable lab results and switched to telehealth visits instead. For those who needed blood draws, we used local labs closer to the patient’s home to minimize their exposure and transportation requirements.

When treatment cannot be deferred, we’ve recommended starting patients on therapies that require fewer in-person visits and are less immune suppressive. We recommended oncologists consider Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib and acalabrutinib, as well as venetoclax. Some research suggests these inhibitors may be protective against COVID-19 by blunting a patient’s hyperinflammatory response to the virus. These drugs also require minimal routine treatment and lab visits, which helps limit patients’ potential exposure to COVID-19.

But there are risks to waiting. Even during the peak of the pandemic here in Seattle, if patients needed treatment immediately, we did not delay. Patients with significant drops in their platelet or neutrophil count or those with bulky disease, for instance, do require therapy.

It’s important to mention that we did have bad experiences with patients who needed immediate treatment and their treating physicians decided to wait because of COVID-19 risks. These patients who came in with aggressive CLL and experienced delays in care had much more complicated CLL treatment than if they had started treatment earlier.

When organ function became abnormal, for example, some patients could no longer receive certain therapies. If someone’s kidney function becomes abnormal, I wouldn’t recommend giving a drug like venetoclax. Although rare, some patients on venetoclax develop tumor lysis syndrome, which can lead to kidney failure.

Bottom line: Don’t just assume it’s a low-grade disease and that you can wait.



What about patients already receiving treatment for CLL who are free of COVID-19?

For patients on active treatment, we suggested stopping or holding treatment with monoclonal antibodies, such as rituximab and obinutuzumab, and chemotherapy regimens, such as idelalisib plus rituximab and duvelisib, when possible. We recommended oncologists consider continuing treatment for patients on BTK inhibitors.



What happens if a patient with CLL tests positive for COVID-19?

If a patient tests positive for COVID-19 but is not yet on CLL treatment, we recommend postponing CLL care until they’ve recovered from the infection. If a patient is already receiving treatment, the recommendations are similar to those above for COVID-19–negative patients: Delay care for those on chemotherapy and monoclonal antibodies, but consider continuing treatment for patients on BTK inhibitors.
 

The expert opinion was submitted in May and ultimately published in August. How has our understanding of treating CLL during the pandemic changed since then? Would you change any recommendations?

When we published this paper, it was still early on in the pandemic, and we didn’t know as much about COVID-19 and CLL as we do now. Since we published the recommendations, we have received confirmation from several studies that patients with cancer have a more complicated course of COVID-19 and have worse outcomes. But I believe the recommendations we devised early in the pandemic still hold now. Decisions about delivering treatment should be influenced by the local COVID-19 numbers and hospital resources as well as the patient’s specific situation – whether they have more stable disease and can delay or postpone care or whether they need more immediate attention.

With a further surge in cases predicted as we move even deeper into flu season, what would you recommend for initiating treatment in newly diagnosed patients?

The pandemic has created a very fluid situation for treating CLL. What’s happening now in Seattle may not be the same story in New York, California, or elsewhere. In early November [when Dr. Shadman was first contacted], in Seattle, we were not postponing care because our COVID-19 numbers were fairly good. But, as of mid December, that is starting to change as the COVID-19 numbers fluctuate.
 

If we do experience a second peak of COVID-19 cases, we would need to modify our practice as we did during the initial surge earlier this year. That would mean avoiding treatment with monoclonal antibodies and chemotherapy, as well as minimizing blood draws and drugs that require frequent in-person visits.
 

How important is it for patients to be vaccinated against COVID-19?

There are two key things to consider about a vaccine. Is the vaccine safe from the general safety standpoint that everyone is worried about? And if the vaccine is not harmful, will it work in patients will CLL?

Because we don’t yet know the complete side-effect profile of a COVID-19 vaccine, we would need to assess each patient’s condition to limit adverse reactions and to see whether the vaccine alters a patient’s immune response to the CLL drug they’re taking.

At the University of Washington, Seattle, we have a plan to start studying the effectiveness of the Pfizer and Moderna vaccines in patients with CLL – carefully assessing patients’ response to the vaccine in terms of antibody response. We already know, based on small studies, that the antibody response to the flu vaccine, for instance, is not as strong in patients with CLL, compared to those without. But, overall, as long as the vaccine won’t cause harm, I would recommend my patients get it.

Dr. Shadman has disclosed no relevant financial relationships.

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

COVID-19 has thrown a wrench in standard treatment protocols for patients with chronic lymphocytic leukemia (CLL). These patients already face a greater risk of dying from infections, and recent research suggests they tend to have risk factors that increase their likelihood of complications and death from COVID-19.

In August, a group of oncologists from the United States and Europe published a literature-informed expert opinion to help their colleagues navigate this new CLL treatment landscape. It offers a roadmap for balancing patients’ therapeutic needs against their risk for viral infection and outlines the safest course of action for patients who test positive for COVID-19.

Mazyar Shadman, MD, MPH, an associate professor in the Clinical Research Division of the Fred Hutchinson Cancer Research Center and the Division of Medical Oncology at the University of Washington School of Medicine, in Seattle, Washington, was contacted for comment to break down what clinicians need to know about treating CLL during the pandemic. This interview has been edited for length and clarity.
 

Question: What prompted you and colleagues from the United States and Europe to write these recommendations?

Dr. Shadman: When we began the collaboration earlier this year, our colleagues in Italy and the rest of Europe had more experience with COVID-19, so they led the effort. We wanted to help oncologists manage their patients with CLL during the pandemic based on the evidence we had at the time and the unknowns we faced.
 

What’s an example of how the available evidence informed your recommendations?

At the time, we didn’t know whether patients with CLL were more likely to get COVID-19, compared to the general population, but we did have evidence already that cancer increases patients’ risk of bad outcomes and death from COVID-19. CLL, for example, can increase risk factors for infection, including hypogammaglobulinemia, innate immune dysfunction, and neutropenia, which may be exacerbated by anticancer treatments. Patients’ existing immune suppression might prevent or delay their ability to react to or cope with the virus. And many patients with CLL have other conditions that increase their risk of a severe response to COVID-19, including older age (70% of CLL patients are older than 65 years), hypertension (21%), and diabetes (26%).

These factors informed our recommendations to limit patients’ exposure to COVID-19 by reducing or postponing the number of in-person visits and routine in-hospital follow-ups, especially if they could be substituted with virtual check-ins.
 

The expert opinion recommendations are divided into three main categories: patients who are newly diagnosed with CLL but have not begun receiving therapy, those already receiving therapy but are free of COVID-19, and those who test positive for COVID-19. Let’s start with the first category. What do the recommendations say about waiting versus proceeding for newly diagnosed patients?

Our priority was balancing the negative impacts of getting COVID-19 with the negative impacts of postponing cancer treatment. We suggested taking each new CLL case on a patient-by-patient basis to determine who needed treatment tomorrow and who could wait a few weeks or months. Fortunately, CLL rarely requires immediate therapy, so the preference was to postpone treatment a few weeks, depending on the local COVID-19 outbreak situation.

In my practice, for instance, we tried to postpone visits as much as we could. Before the pandemic, patients with CLL in the watch-and-wait phase – those diagnosed but who don’t require treatment immediately – would come in for bloodwork and exams every 3-6 months. But when the pandemic hit, we skipped 3-month visits for patients with stable lab results and switched to telehealth visits instead. For those who needed blood draws, we used local labs closer to the patient’s home to minimize their exposure and transportation requirements.

When treatment cannot be deferred, we’ve recommended starting patients on therapies that require fewer in-person visits and are less immune suppressive. We recommended oncologists consider Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib and acalabrutinib, as well as venetoclax. Some research suggests these inhibitors may be protective against COVID-19 by blunting a patient’s hyperinflammatory response to the virus. These drugs also require minimal routine treatment and lab visits, which helps limit patients’ potential exposure to COVID-19.

But there are risks to waiting. Even during the peak of the pandemic here in Seattle, if patients needed treatment immediately, we did not delay. Patients with significant drops in their platelet or neutrophil count or those with bulky disease, for instance, do require therapy.

It’s important to mention that we did have bad experiences with patients who needed immediate treatment and their treating physicians decided to wait because of COVID-19 risks. These patients who came in with aggressive CLL and experienced delays in care had much more complicated CLL treatment than if they had started treatment earlier.

When organ function became abnormal, for example, some patients could no longer receive certain therapies. If someone’s kidney function becomes abnormal, I wouldn’t recommend giving a drug like venetoclax. Although rare, some patients on venetoclax develop tumor lysis syndrome, which can lead to kidney failure.

Bottom line: Don’t just assume it’s a low-grade disease and that you can wait.



What about patients already receiving treatment for CLL who are free of COVID-19?

For patients on active treatment, we suggested stopping or holding treatment with monoclonal antibodies, such as rituximab and obinutuzumab, and chemotherapy regimens, such as idelalisib plus rituximab and duvelisib, when possible. We recommended oncologists consider continuing treatment for patients on BTK inhibitors.



What happens if a patient with CLL tests positive for COVID-19?

If a patient tests positive for COVID-19 but is not yet on CLL treatment, we recommend postponing CLL care until they’ve recovered from the infection. If a patient is already receiving treatment, the recommendations are similar to those above for COVID-19–negative patients: Delay care for those on chemotherapy and monoclonal antibodies, but consider continuing treatment for patients on BTK inhibitors.
 

The expert opinion was submitted in May and ultimately published in August. How has our understanding of treating CLL during the pandemic changed since then? Would you change any recommendations?

When we published this paper, it was still early on in the pandemic, and we didn’t know as much about COVID-19 and CLL as we do now. Since we published the recommendations, we have received confirmation from several studies that patients with cancer have a more complicated course of COVID-19 and have worse outcomes. But I believe the recommendations we devised early in the pandemic still hold now. Decisions about delivering treatment should be influenced by the local COVID-19 numbers and hospital resources as well as the patient’s specific situation – whether they have more stable disease and can delay or postpone care or whether they need more immediate attention.

With a further surge in cases predicted as we move even deeper into flu season, what would you recommend for initiating treatment in newly diagnosed patients?

The pandemic has created a very fluid situation for treating CLL. What’s happening now in Seattle may not be the same story in New York, California, or elsewhere. In early November [when Dr. Shadman was first contacted], in Seattle, we were not postponing care because our COVID-19 numbers were fairly good. But, as of mid December, that is starting to change as the COVID-19 numbers fluctuate.
 

If we do experience a second peak of COVID-19 cases, we would need to modify our practice as we did during the initial surge earlier this year. That would mean avoiding treatment with monoclonal antibodies and chemotherapy, as well as minimizing blood draws and drugs that require frequent in-person visits.
 

How important is it for patients to be vaccinated against COVID-19?

There are two key things to consider about a vaccine. Is the vaccine safe from the general safety standpoint that everyone is worried about? And if the vaccine is not harmful, will it work in patients will CLL?

Because we don’t yet know the complete side-effect profile of a COVID-19 vaccine, we would need to assess each patient’s condition to limit adverse reactions and to see whether the vaccine alters a patient’s immune response to the CLL drug they’re taking.

At the University of Washington, Seattle, we have a plan to start studying the effectiveness of the Pfizer and Moderna vaccines in patients with CLL – carefully assessing patients’ response to the vaccine in terms of antibody response. We already know, based on small studies, that the antibody response to the flu vaccine, for instance, is not as strong in patients with CLL, compared to those without. But, overall, as long as the vaccine won’t cause harm, I would recommend my patients get it.

Dr. Shadman has disclosed no relevant financial relationships.

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

COVID-19 has thrown a wrench in standard treatment protocols for patients with chronic lymphocytic leukemia (CLL). These patients already face a greater risk of dying from infections, and recent research suggests they tend to have risk factors that increase their likelihood of complications and death from COVID-19.

In August, a group of oncologists from the United States and Europe published a literature-informed expert opinion to help their colleagues navigate this new CLL treatment landscape. It offers a roadmap for balancing patients’ therapeutic needs against their risk for viral infection and outlines the safest course of action for patients who test positive for COVID-19.

Mazyar Shadman, MD, MPH, an associate professor in the Clinical Research Division of the Fred Hutchinson Cancer Research Center and the Division of Medical Oncology at the University of Washington School of Medicine, in Seattle, Washington, was contacted for comment to break down what clinicians need to know about treating CLL during the pandemic. This interview has been edited for length and clarity.
 

Question: What prompted you and colleagues from the United States and Europe to write these recommendations?

Dr. Shadman: When we began the collaboration earlier this year, our colleagues in Italy and the rest of Europe had more experience with COVID-19, so they led the effort. We wanted to help oncologists manage their patients with CLL during the pandemic based on the evidence we had at the time and the unknowns we faced.
 

What’s an example of how the available evidence informed your recommendations?

At the time, we didn’t know whether patients with CLL were more likely to get COVID-19, compared to the general population, but we did have evidence already that cancer increases patients’ risk of bad outcomes and death from COVID-19. CLL, for example, can increase risk factors for infection, including hypogammaglobulinemia, innate immune dysfunction, and neutropenia, which may be exacerbated by anticancer treatments. Patients’ existing immune suppression might prevent or delay their ability to react to or cope with the virus. And many patients with CLL have other conditions that increase their risk of a severe response to COVID-19, including older age (70% of CLL patients are older than 65 years), hypertension (21%), and diabetes (26%).

These factors informed our recommendations to limit patients’ exposure to COVID-19 by reducing or postponing the number of in-person visits and routine in-hospital follow-ups, especially if they could be substituted with virtual check-ins.
 

The expert opinion recommendations are divided into three main categories: patients who are newly diagnosed with CLL but have not begun receiving therapy, those already receiving therapy but are free of COVID-19, and those who test positive for COVID-19. Let’s start with the first category. What do the recommendations say about waiting versus proceeding for newly diagnosed patients?

Our priority was balancing the negative impacts of getting COVID-19 with the negative impacts of postponing cancer treatment. We suggested taking each new CLL case on a patient-by-patient basis to determine who needed treatment tomorrow and who could wait a few weeks or months. Fortunately, CLL rarely requires immediate therapy, so the preference was to postpone treatment a few weeks, depending on the local COVID-19 outbreak situation.

In my practice, for instance, we tried to postpone visits as much as we could. Before the pandemic, patients with CLL in the watch-and-wait phase – those diagnosed but who don’t require treatment immediately – would come in for bloodwork and exams every 3-6 months. But when the pandemic hit, we skipped 3-month visits for patients with stable lab results and switched to telehealth visits instead. For those who needed blood draws, we used local labs closer to the patient’s home to minimize their exposure and transportation requirements.

When treatment cannot be deferred, we’ve recommended starting patients on therapies that require fewer in-person visits and are less immune suppressive. We recommended oncologists consider Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib and acalabrutinib, as well as venetoclax. Some research suggests these inhibitors may be protective against COVID-19 by blunting a patient’s hyperinflammatory response to the virus. These drugs also require minimal routine treatment and lab visits, which helps limit patients’ potential exposure to COVID-19.

But there are risks to waiting. Even during the peak of the pandemic here in Seattle, if patients needed treatment immediately, we did not delay. Patients with significant drops in their platelet or neutrophil count or those with bulky disease, for instance, do require therapy.

It’s important to mention that we did have bad experiences with patients who needed immediate treatment and their treating physicians decided to wait because of COVID-19 risks. These patients who came in with aggressive CLL and experienced delays in care had much more complicated CLL treatment than if they had started treatment earlier.

When organ function became abnormal, for example, some patients could no longer receive certain therapies. If someone’s kidney function becomes abnormal, I wouldn’t recommend giving a drug like venetoclax. Although rare, some patients on venetoclax develop tumor lysis syndrome, which can lead to kidney failure.

Bottom line: Don’t just assume it’s a low-grade disease and that you can wait.



What about patients already receiving treatment for CLL who are free of COVID-19?

For patients on active treatment, we suggested stopping or holding treatment with monoclonal antibodies, such as rituximab and obinutuzumab, and chemotherapy regimens, such as idelalisib plus rituximab and duvelisib, when possible. We recommended oncologists consider continuing treatment for patients on BTK inhibitors.



What happens if a patient with CLL tests positive for COVID-19?

If a patient tests positive for COVID-19 but is not yet on CLL treatment, we recommend postponing CLL care until they’ve recovered from the infection. If a patient is already receiving treatment, the recommendations are similar to those above for COVID-19–negative patients: Delay care for those on chemotherapy and monoclonal antibodies, but consider continuing treatment for patients on BTK inhibitors.
 

The expert opinion was submitted in May and ultimately published in August. How has our understanding of treating CLL during the pandemic changed since then? Would you change any recommendations?

When we published this paper, it was still early on in the pandemic, and we didn’t know as much about COVID-19 and CLL as we do now. Since we published the recommendations, we have received confirmation from several studies that patients with cancer have a more complicated course of COVID-19 and have worse outcomes. But I believe the recommendations we devised early in the pandemic still hold now. Decisions about delivering treatment should be influenced by the local COVID-19 numbers and hospital resources as well as the patient’s specific situation – whether they have more stable disease and can delay or postpone care or whether they need more immediate attention.

With a further surge in cases predicted as we move even deeper into flu season, what would you recommend for initiating treatment in newly diagnosed patients?

The pandemic has created a very fluid situation for treating CLL. What’s happening now in Seattle may not be the same story in New York, California, or elsewhere. In early November [when Dr. Shadman was first contacted], in Seattle, we were not postponing care because our COVID-19 numbers were fairly good. But, as of mid December, that is starting to change as the COVID-19 numbers fluctuate.
 

If we do experience a second peak of COVID-19 cases, we would need to modify our practice as we did during the initial surge earlier this year. That would mean avoiding treatment with monoclonal antibodies and chemotherapy, as well as minimizing blood draws and drugs that require frequent in-person visits.
 

How important is it for patients to be vaccinated against COVID-19?

There are two key things to consider about a vaccine. Is the vaccine safe from the general safety standpoint that everyone is worried about? And if the vaccine is not harmful, will it work in patients will CLL?

Because we don’t yet know the complete side-effect profile of a COVID-19 vaccine, we would need to assess each patient’s condition to limit adverse reactions and to see whether the vaccine alters a patient’s immune response to the CLL drug they’re taking.

At the University of Washington, Seattle, we have a plan to start studying the effectiveness of the Pfizer and Moderna vaccines in patients with CLL – carefully assessing patients’ response to the vaccine in terms of antibody response. We already know, based on small studies, that the antibody response to the flu vaccine, for instance, is not as strong in patients with CLL, compared to those without. But, overall, as long as the vaccine won’t cause harm, I would recommend my patients get it.

Dr. Shadman has disclosed no relevant financial relationships.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

In heavily pretreated pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL), venetoclax plus navitoclax with chemotherapy was well tolerated with promising responses, according to results of a phase 1 trial. Delayed count recovery, however, stated lead author Jeffrey E. Rubnitz, MD, PhD, St. Jude’s Children’s Research Hospital, Memphis, remained a key safety concern.
 

Unmet medical need

Despite intensive chemotherapy and novel therapeutics, Dr. Rubnitz said in a virtual oral presentation at the annual meeting of the American Society of Hematology, patients with relapsed or refractory ALL and LL have a poor prognosis and represent an unmet medical need. Venetoclax, a potent, highly selective oral B-cell lymphoma 2 inhibitor, and navitoclax, an oral BCL-2, BCL-XL, and BCL-W inhibitor, directly bind their BCL-2 family member targets to promote apoptosis. In ALL preclinical models, venetoclax and navitoclax have demonstrated antileukemic effects, which suggests dependence on BCL-2 family members. Venetoclax efficacy associated with BCL-2 family inhibition may be potentiated and dose-limiting thrombocytopenia associated with standard-dose navitoclax monotherapy may be avoided by adding venetoclax to low-dose navitoclax. Previous reports of an ongoing phase 1, multicenter, open-label, dose-escalation study in an adult and pediatric population (NCT03181126), Dr. Rubnitz noted, showed the venetoclax/navitoclax/chemotherapy combination to be well tolerated with promising response rates. In the current report, Dr. Rubnitz presented data on the safety, tolerability, pharmacokinetics, and antitumor activity of the triplet regimen in the subgroup of pediatric patients.

The study included pediatric patients (ages, 4-18 years and weight ≥20 kg) receiving venetoclax (weight-adjusted equivalent of 400 mg daily) and navitoclax at three dose levels (25, 50, 100 mg) for patients weighing ≥45 kg and two dose levels (25, 50 mg) for patients weighing <45 kg. At investigator’s discretion, patients could receive chemotherapy (polyethylene glycosylated–asparaginase, vincristine, and dexamethasone). The primary outcomes were safety (including incidence of dose-limiting toxicities and adverse events) and pharmacokinetics. A safety expansion cohort assessed a 21-day dosing schedule of venetoclax at 400 mg followed by 7 days off plus navitoclax at 50 mg (patients ≥45 kg) or 25 mg (patients <45 kg).

Investigators enrolled 18 patients <18 years (median age, 10 years; range, 6-16; 56% male), with 12 in the dose-escalation cohort and 6 in the safety-expansion cohort. Three patients had prior chimeric antigen receptor (CAR) T treatment and four had received prior stem cell transplantation. In the overall cohort, B-cell ALL was most common (n = 13, 72%), with T-cell ALL (n = 3, 17%) and LL (n = 2, 11%) following. The median number of prior therapies was 2 (range 1-6). All patients received chemotherapy.
 

Grade 3-4 adverse events

Venetoclax-related grade 3-4 adverse events occurred in 56% of patients. Similarly, navitoclax-related grade 3-4 events were reported in 56% of patients. Navitoclax dose-limiting toxicities occurred in two patients (11%), delayed count recovery on 25 mg and sepsis on 50 mg. No grade 5 adverse events and tumor lysis syndrome were reported.

Among secondary endpoint efficacy parameters, complete responses, CRs with incomplete marrow recovery (CRi) and CRs without platelet recovery (CRp) combined occurred in 62% of B-ALL patients (8/13), 33% of T-cell ALL patients (1/3) and in 50% of LL patients (1/2). Separately, CRs/CRis/CRps occurred in 33%/22%/0% of all patients, respectively.

Subsequently, 5 of 18 (28%) of patients proceeded to stem cell transplantation and 3 (17%) to CAR T. Eight patients (44%) died from disease progression.
 

BH3 profiling

BH3 profiling revealed that at baseline, patients with B-cell ALL had more diversity in BCL-2 and BCL-XL dependency than did patients with T-cell ALL or early T-cell precursor ALL. The fact that responses were observed in patients who were BCL-2 or BCL-XL dependent, Dr. Rubnitz said, supports the use of venetoclax plus navitoclax in these patients. Analysis of these results led to a recommended phase 2 dose for pediatric patients of 400 mg venetoclax with 25 mg navitoclax (for patients weighing <45 kg) or 50 mg navitoclax (for patients weighing 45 kg or more).

Dr. Rubnitz concluded: “Venetoclax plus navitoclax plus chemotherapy was well tolerated in pediatric patients with relapsed/refractory ALL or LL, with promising response rates observed in a heavily pretreated pediatric population.”

Asked whether the combination might be used also before the refractory setting, in a minimal residual disease (MRD) setting, Dr. Rubnitz replied: “We have a lot of safety data on venetoclax but very little on navitoclax. The next trial, being developed by Seth Karol, MD, will include relapsed patients. MRD-positive patients will also be eligible for enrollment.” To a further question as to whether guiding titration via BH3 profiling would lead to improved outcomes, Dr. Rubnitz said, “I think BH3 profiling can be used to identify which patients will respond to these drugs, but we are still a long way from using it for titrating the doses and dose ratios for the two drugs.”

Dr. Rubnitz disclosed research funding from AbbVie.

SOURCE: Rubnitz JE et al. ASH 2020, Abstract 466.

In heavily pretreated pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL), venetoclax plus navitoclax with chemotherapy was well tolerated with promising responses, according to results of a phase 1 trial. Delayed count recovery, however, stated lead author Jeffrey E. Rubnitz, MD, PhD, St. Jude’s Children’s Research Hospital, Memphis, remained a key safety concern.
 

Unmet medical need

Despite intensive chemotherapy and novel therapeutics, Dr. Rubnitz said in a virtual oral presentation at the annual meeting of the American Society of Hematology, patients with relapsed or refractory ALL and LL have a poor prognosis and represent an unmet medical need. Venetoclax, a potent, highly selective oral B-cell lymphoma 2 inhibitor, and navitoclax, an oral BCL-2, BCL-XL, and BCL-W inhibitor, directly bind their BCL-2 family member targets to promote apoptosis. In ALL preclinical models, venetoclax and navitoclax have demonstrated antileukemic effects, which suggests dependence on BCL-2 family members. Venetoclax efficacy associated with BCL-2 family inhibition may be potentiated and dose-limiting thrombocytopenia associated with standard-dose navitoclax monotherapy may be avoided by adding venetoclax to low-dose navitoclax. Previous reports of an ongoing phase 1, multicenter, open-label, dose-escalation study in an adult and pediatric population (NCT03181126), Dr. Rubnitz noted, showed the venetoclax/navitoclax/chemotherapy combination to be well tolerated with promising response rates. In the current report, Dr. Rubnitz presented data on the safety, tolerability, pharmacokinetics, and antitumor activity of the triplet regimen in the subgroup of pediatric patients.

The study included pediatric patients (ages, 4-18 years and weight ≥20 kg) receiving venetoclax (weight-adjusted equivalent of 400 mg daily) and navitoclax at three dose levels (25, 50, 100 mg) for patients weighing ≥45 kg and two dose levels (25, 50 mg) for patients weighing <45 kg. At investigator’s discretion, patients could receive chemotherapy (polyethylene glycosylated–asparaginase, vincristine, and dexamethasone). The primary outcomes were safety (including incidence of dose-limiting toxicities and adverse events) and pharmacokinetics. A safety expansion cohort assessed a 21-day dosing schedule of venetoclax at 400 mg followed by 7 days off plus navitoclax at 50 mg (patients ≥45 kg) or 25 mg (patients <45 kg).

Investigators enrolled 18 patients <18 years (median age, 10 years; range, 6-16; 56% male), with 12 in the dose-escalation cohort and 6 in the safety-expansion cohort. Three patients had prior chimeric antigen receptor (CAR) T treatment and four had received prior stem cell transplantation. In the overall cohort, B-cell ALL was most common (n = 13, 72%), with T-cell ALL (n = 3, 17%) and LL (n = 2, 11%) following. The median number of prior therapies was 2 (range 1-6). All patients received chemotherapy.
 

Grade 3-4 adverse events

Venetoclax-related grade 3-4 adverse events occurred in 56% of patients. Similarly, navitoclax-related grade 3-4 events were reported in 56% of patients. Navitoclax dose-limiting toxicities occurred in two patients (11%), delayed count recovery on 25 mg and sepsis on 50 mg. No grade 5 adverse events and tumor lysis syndrome were reported.

Among secondary endpoint efficacy parameters, complete responses, CRs with incomplete marrow recovery (CRi) and CRs without platelet recovery (CRp) combined occurred in 62% of B-ALL patients (8/13), 33% of T-cell ALL patients (1/3) and in 50% of LL patients (1/2). Separately, CRs/CRis/CRps occurred in 33%/22%/0% of all patients, respectively.

Subsequently, 5 of 18 (28%) of patients proceeded to stem cell transplantation and 3 (17%) to CAR T. Eight patients (44%) died from disease progression.
 

BH3 profiling

BH3 profiling revealed that at baseline, patients with B-cell ALL had more diversity in BCL-2 and BCL-XL dependency than did patients with T-cell ALL or early T-cell precursor ALL. The fact that responses were observed in patients who were BCL-2 or BCL-XL dependent, Dr. Rubnitz said, supports the use of venetoclax plus navitoclax in these patients. Analysis of these results led to a recommended phase 2 dose for pediatric patients of 400 mg venetoclax with 25 mg navitoclax (for patients weighing <45 kg) or 50 mg navitoclax (for patients weighing 45 kg or more).

Dr. Rubnitz concluded: “Venetoclax plus navitoclax plus chemotherapy was well tolerated in pediatric patients with relapsed/refractory ALL or LL, with promising response rates observed in a heavily pretreated pediatric population.”

Asked whether the combination might be used also before the refractory setting, in a minimal residual disease (MRD) setting, Dr. Rubnitz replied: “We have a lot of safety data on venetoclax but very little on navitoclax. The next trial, being developed by Seth Karol, MD, will include relapsed patients. MRD-positive patients will also be eligible for enrollment.” To a further question as to whether guiding titration via BH3 profiling would lead to improved outcomes, Dr. Rubnitz said, “I think BH3 profiling can be used to identify which patients will respond to these drugs, but we are still a long way from using it for titrating the doses and dose ratios for the two drugs.”

Dr. Rubnitz disclosed research funding from AbbVie.

SOURCE: Rubnitz JE et al. ASH 2020, Abstract 466.

In heavily pretreated pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL), venetoclax plus navitoclax with chemotherapy was well tolerated with promising responses, according to results of a phase 1 trial. Delayed count recovery, however, stated lead author Jeffrey E. Rubnitz, MD, PhD, St. Jude’s Children’s Research Hospital, Memphis, remained a key safety concern.
 

Unmet medical need

Despite intensive chemotherapy and novel therapeutics, Dr. Rubnitz said in a virtual oral presentation at the annual meeting of the American Society of Hematology, patients with relapsed or refractory ALL and LL have a poor prognosis and represent an unmet medical need. Venetoclax, a potent, highly selective oral B-cell lymphoma 2 inhibitor, and navitoclax, an oral BCL-2, BCL-XL, and BCL-W inhibitor, directly bind their BCL-2 family member targets to promote apoptosis. In ALL preclinical models, venetoclax and navitoclax have demonstrated antileukemic effects, which suggests dependence on BCL-2 family members. Venetoclax efficacy associated with BCL-2 family inhibition may be potentiated and dose-limiting thrombocytopenia associated with standard-dose navitoclax monotherapy may be avoided by adding venetoclax to low-dose navitoclax. Previous reports of an ongoing phase 1, multicenter, open-label, dose-escalation study in an adult and pediatric population (NCT03181126), Dr. Rubnitz noted, showed the venetoclax/navitoclax/chemotherapy combination to be well tolerated with promising response rates. In the current report, Dr. Rubnitz presented data on the safety, tolerability, pharmacokinetics, and antitumor activity of the triplet regimen in the subgroup of pediatric patients.

The study included pediatric patients (ages, 4-18 years and weight ≥20 kg) receiving venetoclax (weight-adjusted equivalent of 400 mg daily) and navitoclax at three dose levels (25, 50, 100 mg) for patients weighing ≥45 kg and two dose levels (25, 50 mg) for patients weighing <45 kg. At investigator’s discretion, patients could receive chemotherapy (polyethylene glycosylated–asparaginase, vincristine, and dexamethasone). The primary outcomes were safety (including incidence of dose-limiting toxicities and adverse events) and pharmacokinetics. A safety expansion cohort assessed a 21-day dosing schedule of venetoclax at 400 mg followed by 7 days off plus navitoclax at 50 mg (patients ≥45 kg) or 25 mg (patients <45 kg).

Investigators enrolled 18 patients <18 years (median age, 10 years; range, 6-16; 56% male), with 12 in the dose-escalation cohort and 6 in the safety-expansion cohort. Three patients had prior chimeric antigen receptor (CAR) T treatment and four had received prior stem cell transplantation. In the overall cohort, B-cell ALL was most common (n = 13, 72%), with T-cell ALL (n = 3, 17%) and LL (n = 2, 11%) following. The median number of prior therapies was 2 (range 1-6). All patients received chemotherapy.
 

Grade 3-4 adverse events

Venetoclax-related grade 3-4 adverse events occurred in 56% of patients. Similarly, navitoclax-related grade 3-4 events were reported in 56% of patients. Navitoclax dose-limiting toxicities occurred in two patients (11%), delayed count recovery on 25 mg and sepsis on 50 mg. No grade 5 adverse events and tumor lysis syndrome were reported.

Among secondary endpoint efficacy parameters, complete responses, CRs with incomplete marrow recovery (CRi) and CRs without platelet recovery (CRp) combined occurred in 62% of B-ALL patients (8/13), 33% of T-cell ALL patients (1/3) and in 50% of LL patients (1/2). Separately, CRs/CRis/CRps occurred in 33%/22%/0% of all patients, respectively.

Subsequently, 5 of 18 (28%) of patients proceeded to stem cell transplantation and 3 (17%) to CAR T. Eight patients (44%) died from disease progression.
 

BH3 profiling

BH3 profiling revealed that at baseline, patients with B-cell ALL had more diversity in BCL-2 and BCL-XL dependency than did patients with T-cell ALL or early T-cell precursor ALL. The fact that responses were observed in patients who were BCL-2 or BCL-XL dependent, Dr. Rubnitz said, supports the use of venetoclax plus navitoclax in these patients. Analysis of these results led to a recommended phase 2 dose for pediatric patients of 400 mg venetoclax with 25 mg navitoclax (for patients weighing <45 kg) or 50 mg navitoclax (for patients weighing 45 kg or more).

Dr. Rubnitz concluded: “Venetoclax plus navitoclax plus chemotherapy was well tolerated in pediatric patients with relapsed/refractory ALL or LL, with promising response rates observed in a heavily pretreated pediatric population.”

Asked whether the combination might be used also before the refractory setting, in a minimal residual disease (MRD) setting, Dr. Rubnitz replied: “We have a lot of safety data on venetoclax but very little on navitoclax. The next trial, being developed by Seth Karol, MD, will include relapsed patients. MRD-positive patients will also be eligible for enrollment.” To a further question as to whether guiding titration via BH3 profiling would lead to improved outcomes, Dr. Rubnitz said, “I think BH3 profiling can be used to identify which patients will respond to these drugs, but we are still a long way from using it for titrating the doses and dose ratios for the two drugs.”

Dr. Rubnitz disclosed research funding from AbbVie.

SOURCE: Rubnitz JE et al. ASH 2020, Abstract 466.

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with sequential blinatumomab is highly effective as frontline therapy for Philadelphia Chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (ALL), according to results of a phase 2 study reported at the annual meeting of the American Society of Hematology.

Favorable minimal residual disease (MRD) negativity and overall survival with low higher-grade toxicities suggest that reductions in chemotherapy in this setting are feasible, said Nicholas J. Short, MD, of the University of Texas MD Anderson Cancer Center, Houston.

While complete response rates with current ALL therapy are 80%-90%, long-term overall survival is only 40%-50%. Blinatumomab, a bispecific T-cell–engaging CD3-CD19 antibody, has been shown to be superior to chemotherapy in relapsed/refractory B-cell ALL, and to produce high rates of MRD eradication, the most important prognostic factor in ALL, Dr. Short said at the meeting, which was held virtually.

The hypothesis of the current study was that early incorporation of blinatumomab with hyper-CVAD in patients with newly diagnosed Ph-negative B-cell ALL would decrease the need for intensive chemotherapy and lead to higher efficacy and cure rates with less myelosuppression. Patients were required to have a performance status of 3 or less, total bilirubin 2 mg/dL or less and creatinine 2 mg/dL or less. Investigators enrolled 38 patients (mean age, 37 years,; range, 17-59) with most (79%) in performance status 0-1. The primary endpoint was relapse-free survival (RFS).
 

Study details

Patients received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to four cycles followed by four cycles of blinatumomab at standard doses. Those with CD20-positive disease (1% or greater percentage of the cells) received eight doses of ofatumumab or rituximab, and prophylactic intrathecal chemotherapy was given eight times in the first four cycles. Maintenance consisted of alternating blocks of POMP (6-mercaptopurine, vincristine, methotrexate, prednisone) and blinatumomab. When two patients with high-risk features experienced early relapse, investigators amended the protocol to allow blinatumomab after only two cycles of hyper-CVAD in those with high-risk features (e.g., CRLF2 positive by flow cytometry, complex karyotype, KMT2A rearranged, low hypodiploidy/near triploidy, TP53 mutation, or persistent MRD). Nineteen patients (56%) had at least one high-risk feature, and 82% received ofatumumab or rituximab. Six patients were in complete remission at the start of the study (four of them MRD negative).

Complete responses

After induction, complete responses were achieved in 81% (26/32), with all patients achieving a complete response at some point, according to Dr. Short. The MRD negativity rate was 71% (24/34) after induction and 97% (33/34) at any time. Among the 38 patients, all with complete response at median follow-up of 24 months (range, 2-45), relapses occurred only in those 5 patients with high-risk features. Twelve patients underwent transplant in the first remission. Two relapsed, both with high-risk features. The other 21 patients had ongoing complete responses.

RFS at 1- and 2-years was 80% and 71%, respectively. Five among seven relapses were without hematopoietic stem cell transplantation, and 2 were post HSCT. Two deaths occurred in patients with complete responses (one pulmonary embolism and one with post-HSCT complications). Overall survival at 1 and 2 years was 85% and 80%, respectively, with the 2-year rate comparable with prior reports for hyper-CVAD plus ofatumumab, Dr. Short said.

The most common nonhematologic grade 3-4 adverse events with hyper-CVAD plus blinatumomab were ALT/AST elevation (24%) and hyperglycemia (21%). The overall cytokine release syndrome rate was 13%, with 3% for higher-grade reactions. The rate for blinatumomab-related neurologic events was 45% overall and 13% for higher grades, with 1 discontinuation attributed to grade 2 encephalopathy and dysphasia.

“Overall, this study shows the potential benefit of incorporating frontline blinatumomab into the treatment of younger adults with newly diagnosed Philadelphia chromosome–negative B-cell lymphoma, and shows, as well, that reduction of chemotherapy in this context is feasible,” Dr. Short stated.

“Ultimately, often for any patients with acute leukemias and ALL, our only chance to cure them is in the frontline setting, so our approach is to include all of the most effective agents we have. So that means including blinatumomab in all of our frontline regimens in clinical trials – and now we’ve amended that to add inotuzumab ozogamicin with the goal of deepening responses and increasing cure rates,” he added.

Dr. Short reported consulting with Takeda Oncology and Astrazeneca, and receiving research funding and honoraria from Amgen, Astella, and Takeda Oncology.

SOURCE: Short NG et al. ASH 2020, Abstract 464.

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with sequential blinatumomab is highly effective as frontline therapy for Philadelphia Chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (ALL), according to results of a phase 2 study reported at the annual meeting of the American Society of Hematology.

Favorable minimal residual disease (MRD) negativity and overall survival with low higher-grade toxicities suggest that reductions in chemotherapy in this setting are feasible, said Nicholas J. Short, MD, of the University of Texas MD Anderson Cancer Center, Houston.

While complete response rates with current ALL therapy are 80%-90%, long-term overall survival is only 40%-50%. Blinatumomab, a bispecific T-cell–engaging CD3-CD19 antibody, has been shown to be superior to chemotherapy in relapsed/refractory B-cell ALL, and to produce high rates of MRD eradication, the most important prognostic factor in ALL, Dr. Short said at the meeting, which was held virtually.

The hypothesis of the current study was that early incorporation of blinatumomab with hyper-CVAD in patients with newly diagnosed Ph-negative B-cell ALL would decrease the need for intensive chemotherapy and lead to higher efficacy and cure rates with less myelosuppression. Patients were required to have a performance status of 3 or less, total bilirubin 2 mg/dL or less and creatinine 2 mg/dL or less. Investigators enrolled 38 patients (mean age, 37 years,; range, 17-59) with most (79%) in performance status 0-1. The primary endpoint was relapse-free survival (RFS).
 

Study details

Patients received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to four cycles followed by four cycles of blinatumomab at standard doses. Those with CD20-positive disease (1% or greater percentage of the cells) received eight doses of ofatumumab or rituximab, and prophylactic intrathecal chemotherapy was given eight times in the first four cycles. Maintenance consisted of alternating blocks of POMP (6-mercaptopurine, vincristine, methotrexate, prednisone) and blinatumomab. When two patients with high-risk features experienced early relapse, investigators amended the protocol to allow blinatumomab after only two cycles of hyper-CVAD in those with high-risk features (e.g., CRLF2 positive by flow cytometry, complex karyotype, KMT2A rearranged, low hypodiploidy/near triploidy, TP53 mutation, or persistent MRD). Nineteen patients (56%) had at least one high-risk feature, and 82% received ofatumumab or rituximab. Six patients were in complete remission at the start of the study (four of them MRD negative).

Complete responses

After induction, complete responses were achieved in 81% (26/32), with all patients achieving a complete response at some point, according to Dr. Short. The MRD negativity rate was 71% (24/34) after induction and 97% (33/34) at any time. Among the 38 patients, all with complete response at median follow-up of 24 months (range, 2-45), relapses occurred only in those 5 patients with high-risk features. Twelve patients underwent transplant in the first remission. Two relapsed, both with high-risk features. The other 21 patients had ongoing complete responses.

RFS at 1- and 2-years was 80% and 71%, respectively. Five among seven relapses were without hematopoietic stem cell transplantation, and 2 were post HSCT. Two deaths occurred in patients with complete responses (one pulmonary embolism and one with post-HSCT complications). Overall survival at 1 and 2 years was 85% and 80%, respectively, with the 2-year rate comparable with prior reports for hyper-CVAD plus ofatumumab, Dr. Short said.

The most common nonhematologic grade 3-4 adverse events with hyper-CVAD plus blinatumomab were ALT/AST elevation (24%) and hyperglycemia (21%). The overall cytokine release syndrome rate was 13%, with 3% for higher-grade reactions. The rate for blinatumomab-related neurologic events was 45% overall and 13% for higher grades, with 1 discontinuation attributed to grade 2 encephalopathy and dysphasia.

“Overall, this study shows the potential benefit of incorporating frontline blinatumomab into the treatment of younger adults with newly diagnosed Philadelphia chromosome–negative B-cell lymphoma, and shows, as well, that reduction of chemotherapy in this context is feasible,” Dr. Short stated.

“Ultimately, often for any patients with acute leukemias and ALL, our only chance to cure them is in the frontline setting, so our approach is to include all of the most effective agents we have. So that means including blinatumomab in all of our frontline regimens in clinical trials – and now we’ve amended that to add inotuzumab ozogamicin with the goal of deepening responses and increasing cure rates,” he added.

Dr. Short reported consulting with Takeda Oncology and Astrazeneca, and receiving research funding and honoraria from Amgen, Astella, and Takeda Oncology.

SOURCE: Short NG et al. ASH 2020, Abstract 464.

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with sequential blinatumomab is highly effective as frontline therapy for Philadelphia Chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (ALL), according to results of a phase 2 study reported at the annual meeting of the American Society of Hematology.

Favorable minimal residual disease (MRD) negativity and overall survival with low higher-grade toxicities suggest that reductions in chemotherapy in this setting are feasible, said Nicholas J. Short, MD, of the University of Texas MD Anderson Cancer Center, Houston.

While complete response rates with current ALL therapy are 80%-90%, long-term overall survival is only 40%-50%. Blinatumomab, a bispecific T-cell–engaging CD3-CD19 antibody, has been shown to be superior to chemotherapy in relapsed/refractory B-cell ALL, and to produce high rates of MRD eradication, the most important prognostic factor in ALL, Dr. Short said at the meeting, which was held virtually.

The hypothesis of the current study was that early incorporation of blinatumomab with hyper-CVAD in patients with newly diagnosed Ph-negative B-cell ALL would decrease the need for intensive chemotherapy and lead to higher efficacy and cure rates with less myelosuppression. Patients were required to have a performance status of 3 or less, total bilirubin 2 mg/dL or less and creatinine 2 mg/dL or less. Investigators enrolled 38 patients (mean age, 37 years,; range, 17-59) with most (79%) in performance status 0-1. The primary endpoint was relapse-free survival (RFS).
 

Study details

Patients received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to four cycles followed by four cycles of blinatumomab at standard doses. Those with CD20-positive disease (1% or greater percentage of the cells) received eight doses of ofatumumab or rituximab, and prophylactic intrathecal chemotherapy was given eight times in the first four cycles. Maintenance consisted of alternating blocks of POMP (6-mercaptopurine, vincristine, methotrexate, prednisone) and blinatumomab. When two patients with high-risk features experienced early relapse, investigators amended the protocol to allow blinatumomab after only two cycles of hyper-CVAD in those with high-risk features (e.g., CRLF2 positive by flow cytometry, complex karyotype, KMT2A rearranged, low hypodiploidy/near triploidy, TP53 mutation, or persistent MRD). Nineteen patients (56%) had at least one high-risk feature, and 82% received ofatumumab or rituximab. Six patients were in complete remission at the start of the study (four of them MRD negative).

Complete responses

After induction, complete responses were achieved in 81% (26/32), with all patients achieving a complete response at some point, according to Dr. Short. The MRD negativity rate was 71% (24/34) after induction and 97% (33/34) at any time. Among the 38 patients, all with complete response at median follow-up of 24 months (range, 2-45), relapses occurred only in those 5 patients with high-risk features. Twelve patients underwent transplant in the first remission. Two relapsed, both with high-risk features. The other 21 patients had ongoing complete responses.

RFS at 1- and 2-years was 80% and 71%, respectively. Five among seven relapses were without hematopoietic stem cell transplantation, and 2 were post HSCT. Two deaths occurred in patients with complete responses (one pulmonary embolism and one with post-HSCT complications). Overall survival at 1 and 2 years was 85% and 80%, respectively, with the 2-year rate comparable with prior reports for hyper-CVAD plus ofatumumab, Dr. Short said.

The most common nonhematologic grade 3-4 adverse events with hyper-CVAD plus blinatumomab were ALT/AST elevation (24%) and hyperglycemia (21%). The overall cytokine release syndrome rate was 13%, with 3% for higher-grade reactions. The rate for blinatumomab-related neurologic events was 45% overall and 13% for higher grades, with 1 discontinuation attributed to grade 2 encephalopathy and dysphasia.

“Overall, this study shows the potential benefit of incorporating frontline blinatumomab into the treatment of younger adults with newly diagnosed Philadelphia chromosome–negative B-cell lymphoma, and shows, as well, that reduction of chemotherapy in this context is feasible,” Dr. Short stated.

“Ultimately, often for any patients with acute leukemias and ALL, our only chance to cure them is in the frontline setting, so our approach is to include all of the most effective agents we have. So that means including blinatumomab in all of our frontline regimens in clinical trials – and now we’ve amended that to add inotuzumab ozogamicin with the goal of deepening responses and increasing cure rates,” he added.

Dr. Short reported consulting with Takeda Oncology and Astrazeneca, and receiving research funding and honoraria from Amgen, Astella, and Takeda Oncology.

SOURCE: Short NG et al. ASH 2020, Abstract 464.

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.

Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.

“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”

She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.

The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.

Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.

“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
 

Black race a risk factor

For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.

To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.

Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”

Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”

However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).

Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
 

Differences in biomarkers

With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.

On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.

“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.

“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
 

Understudied disparities

Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.

“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”

She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”

The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.

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

Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.

Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.

“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”

She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.

The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.

Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.

“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
 

Black race a risk factor

For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.

To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.

Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”

Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”

However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).

Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
 

Differences in biomarkers

With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.

On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.

“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.

“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
 

Understudied disparities

Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.

“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”

She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”

The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.

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

Black race is the most important risk factor for patients with acute myeloid leukemia (AML) and is associated with poor survival, according to new findings.

Among patients with AML younger than 60 years, the rate of overall 3-year survival was significantly less among Black patients than White patients (34% vs. 43%). The risk for death was 27% higher for Black patients compared with White patients.

“Our study demonstrates the delicate interplay between a variety of factors that influence survival disparities, particularly for younger Black AML patients,” said first author Bhavana Bhatnagar, DO, of the Ohio State University’s Comprehensive Cancer Center, Columbus. “We were able to confirm the impact of socioeconomic factors while also demonstrating that being Black is, in and of itself, an independent poor prognostic variable for survival.”

She noted that the persistently poor outcomes of young Black patients that were seen despite similar treatments in clinical trials strongly suggest that additional factors have a bearing on their survival.

The findings of the study were presented during the plenary session of the annual meeting of the American Society of Hematology, which was held online this year. The study was simultaneously published in Cancer Discovery.

Racial disparities in cancer outcomes remain a challenge. The term “health disparities” describes the differences of health outcomes among different groups, said Chancellor Donald, MD, of Tulane University, New Orleans, who introduced the article at the meeting. “Racial health disparities usually result from an unequal distribution of power and resources, not genetics.

“The examination of health disparities is certainly a worthwhile endeavor,” he continued. “For generations, differences in key health outcomes have negatively impacted the quality of life and shortened the life span of countless individuals. As scientists, clinicians, and invested members of our shared society, we are obligated to obtain a profound understanding of the mechanisms and impact of this morbid reality.”
 

Black race a risk factor

For their study, Dr. Bhatnagar and colleagues conducted a nationwide population analysis using data from the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute to identify 11,190 adults aged 18-60 years who were diagnosed with AML between 1986 and 2015.

To characterize molecular features, they conducted targeted sequencing of 81 genes in 1,339 patients with AML who were treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard-intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. None of these patients received an allogeneic stem cell transplant when they achieved complete remission.

Although overall survival has improved during the past 3 decades, survival disparities between Black and White patients has widened over time (P < .001). The authors found a nonstatistically significant difference in survival between 1986 and 1995 (White patients, n = 1,365; Black patients, n = 160; P = .19). However, the difference was significant between 1996 and 2005 (White patients, n = 2,994; Black patients, n = 480; P = .004). “And it became even more noticeable in the most recent decade,” said Dr. Bhatnagar. “Furthermore, younger Black AML patients were found to have worse survival compared with younger White AML patients.”

Results from the second analysis of patients treated on Alliance protocols did not show any significant differences in early death rates (10% vs. 46%; P = .02) and complete remission rates (71% vs. 71%; P = 1.00). “While relapse rates were slightly higher in Black compared to White patients, this difference did not reach statistical significance,” said Dr. Bhatnagar. “There was also no significant difference in the number of cycles of consolidation chemotherapy administered to these patients.”

However, both disease-free and overall survival were significantly worse for Black patients, suggesting that factors other than treatment selection were likely at play in influencing the survival disparity. The median disease-free survival for Black patients was 0.8 years, vs. 1.4 years for White patients (P = .02). Overall survival was 1.2 years vs. 1.8 years (P = .02).

Relapse rates were slightly higher in Black patients than in White patients, at 71% vs. 59%, but this difference did not reach statistical significance (P = .14).
 

Differences in biomarkers

With regard to underlying molecular differences between Black and White patients, the investigators found that the most common mutations were in NPM1, FLT3-ITD, and DNM3TA. Mutations were detected in more than 20% of Black patients. Other commonly mutated genes were IDH2, NRAS, TET2, IDH1, and TP53, which were mutated in more than 10% of patients. “All of these genes are established commonly mutated genes in AML,” said Bhatnagar.

On univariable and multivariable outcome analyses, which were used to identify clinical or molecular features that had a bearing on outcome, FLT3-ITD and IDH2 mutations were the only mutations associated with a higher risk for death among Black patients.

“This is actually a very important finding, as both FLT3 and IDH2 are now targetable with small-molecule inhibitors,” said Dr. Bhatnagar. “In addition, it is also worth noting that other gene mutations that have known prognostic significance in AML, such as NPM1, as well as RUNX1 and TP53, did not remain in the final statistical model.

“Importantly, our study provides powerful evidence that suggests differences in underlying disease biology between young Black and White AML patients, as evidenced by differences in the frequencies of recurrent gene mutations, “ she said.
 

Understudied disparities

Although the study showed that Black patients had worse outcomes, “surprisingly, the authors found these outcomes hold even when the patients are participating in clinical trials,” noted Elisa Weiss, PhD, senior vice president of education, services, and health research for the Leukemia and Lymphoma Society.

“The study makes clear that the medical and science community need to do more to better understand the social, economic, environmental, and biological causes of these disparities,” she said in an interview. “In fact, the findings suggest that there are myriad complex and understudied causes of the identified disparities, and they are likely to lie at the intersection of all levels of the social ecology that impact an individual’s ability to access timely and unbiased care, maintain their mental and physical health, and receive needed social support and resources.”

She noted that the Leukemia and Lymphoma Society has an Equity in Access research program that aims to “advance study of underlying causes of inequitable access to care and identify policies, strategies, and interventions that have the potential to reduce inequities and increase access to health care, services, and programs for blood cancer patients and survivors.”

The research was supported in part by the National Cancer Institute of the National Institutes of Health, other institutions, and through several scholar awards. Dr. Bhatnagar has received advisory board honoraria from Novartis, Kite Pharma, Celgene, Astellas, and Cell Therapeutics. Dr. Weiss has disclosed no relevant financial relationships.

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

Among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in the minimal residual disease (MRD) cohort of the phase 2 CAPTIVATE trial, a 1-year disease-free survival (DFS) rate of 95% in those randomized to placebo after 12 cycles of combined ibrutinib plus venetoclax supports a fixed-duration treatment approach, according to William G. Wierda, MD, PhD, University of Texas, MD Anderson Cancer Center, Houston.

Ibrutinib, a once-daily Bruton kinase inhibitor, is the only targeted therapy for first-line treatment of CLL that has demonstrated significant overall survival benefit in randomized phase 3 studies, Dr. Wierda said at the American Society of Hematology annual meeting, held virtually.

Ibrutinib and venetoclax have synergistic and complementary antitumor activity, he noted, through mobilizing and clearing CLL cells from protective niches and disease compartments beyond blood and bone marrow.

Fixed-duration study

CAPTIVATE (PCYC-1142), an international phase 2 study, evaluated first-line treatment with 12 cycles of the ibrutinib/venetoclax combination in MRD and fixed-duration cohorts. The current primary analysis of 1-year DFS from the MRD cohort tested whether the regimen allows for treatment-free remission in the setting of confirmed undetectable MRD (uMRD).

Patients (n = 164, median age 58 years) in the CAPTIVATE study MRD cohort had previously untreated active CLL/SLL requiring treatment per International Workshop on Chronic Lymphocytic Leukemia criteria.

They received 3 cycles of lead-in ibrutinib (420 mg once daily) followed by 12 cycles of ibrutinib (420 mg once daily plus venetoclax ramp-up to 400 mg once daily). Thereafter, in an MRD-guided 1:1 randomization stratified by immunoglobulin heavy chain (IGHV) mutational status, those with confirmed uMRD received either placebo or ibrutinib, and those with uMRD not confirmed received either ibrutinib or ibrutinib plus venetoclax (both open-label).

Among high-risk features in CAPTIVATE subjects, 60% of patients had unmutated IGHV, with del(17p)/TP53 mutation in 20%, del(11Q) in 17%, complex karyotype in 19%, cytopenias in 36%, bulky lymph nodes in 32%, and absolute neutrophil count ≥25x109/L in 76%.
 

Response findings

The ibrutinib lead-in, Dr. Wierda said, reduced tumor lysis syndrome (TLS) risk, shifting 90% of patients with high baseline TLS risk to medium or low-risk categories (from 77 to 51 patients), precluding need for hospitalization with venetoclax initiation.

The rate for best response of uMRD (defined as uMRD over at least 3 cycles in both peripheral blood and bone marrow) in evaluable patients was 75% in peripheral blood (n = 163) and 72% in bone marrow (n = 155).

Confirmed uMRD was achieved in 86/149 (58%), with uMRD not confirmed in 63/149 (uMRD 32% in bone marrow and 48% in peripheral blood). One-year DFS after the further randomization to placebo or ibrutinib in the confirmed uMRD group was 95.3% in the placebo group and 100% in the ibrutinib group (P = .1475). In the uMRD not confirmed group, 30-month progression-free survival (PFS) was 95.2% and 96.7% in the ibrutinib and ibrutinib plus venetoclax groups, respectively. Thirty-month PFS rates in the confirmed uMRD placebo and ibrutinib arms were 95.3% and 100%. “Thirty-month PFS rates were greater than 95% across all randomized arms,” Dr. Wierda stated.

In patients without confirmed uMRD after 12 cycles of combined ibrutinib plus venetoclax, additional randomized treatment led to greater increases in uMRD in the ibrutinib plus venetoclax group than in the ibrutinib alone group (bone marrow additional 10% ibrutinib alone, 34% ibrutinib plus venetoclax; peripheral blood 0% ibrutinib, 19% ibrutinib plus venetoclax).

Adverse events generally decreased after the first 6 months of ibrutinib plus venetoclax treatment, with no new safety signals emerging over time. “There were no safety concerns with this highly active combination of first-line ibrutinib plus venetoclax. It’s an oral, once-daily fixed duration regimen that achieves undetectable MRD in blood or bone marrow in three-fourths of patients after 12 cycles of combined treatment.”

When asked, in a question-and-answer session after his presentation, if the findings were “practice changing,” Dr. Wierda responded: “We need additional data from ongoing studies looking at various combinations of targeted therapy. But this study does clearly show efficacy in terms of depth of remission, and it supports the concept of fixed duration treatment, particularly for those patients who achieved undetectable MRD status.”
 

SOURCE: William G. Wierda, MD, PhD. ASH 2020, Abstract 123.

Among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in the minimal residual disease (MRD) cohort of the phase 2 CAPTIVATE trial, a 1-year disease-free survival (DFS) rate of 95% in those randomized to placebo after 12 cycles of combined ibrutinib plus venetoclax supports a fixed-duration treatment approach, according to William G. Wierda, MD, PhD, University of Texas, MD Anderson Cancer Center, Houston.

Ibrutinib, a once-daily Bruton kinase inhibitor, is the only targeted therapy for first-line treatment of CLL that has demonstrated significant overall survival benefit in randomized phase 3 studies, Dr. Wierda said at the American Society of Hematology annual meeting, held virtually.

Ibrutinib and venetoclax have synergistic and complementary antitumor activity, he noted, through mobilizing and clearing CLL cells from protective niches and disease compartments beyond blood and bone marrow.

Fixed-duration study

CAPTIVATE (PCYC-1142), an international phase 2 study, evaluated first-line treatment with 12 cycles of the ibrutinib/venetoclax combination in MRD and fixed-duration cohorts. The current primary analysis of 1-year DFS from the MRD cohort tested whether the regimen allows for treatment-free remission in the setting of confirmed undetectable MRD (uMRD).

Patients (n = 164, median age 58 years) in the CAPTIVATE study MRD cohort had previously untreated active CLL/SLL requiring treatment per International Workshop on Chronic Lymphocytic Leukemia criteria.

They received 3 cycles of lead-in ibrutinib (420 mg once daily) followed by 12 cycles of ibrutinib (420 mg once daily plus venetoclax ramp-up to 400 mg once daily). Thereafter, in an MRD-guided 1:1 randomization stratified by immunoglobulin heavy chain (IGHV) mutational status, those with confirmed uMRD received either placebo or ibrutinib, and those with uMRD not confirmed received either ibrutinib or ibrutinib plus venetoclax (both open-label).

Among high-risk features in CAPTIVATE subjects, 60% of patients had unmutated IGHV, with del(17p)/TP53 mutation in 20%, del(11Q) in 17%, complex karyotype in 19%, cytopenias in 36%, bulky lymph nodes in 32%, and absolute neutrophil count ≥25x109/L in 76%.
 

Response findings

The ibrutinib lead-in, Dr. Wierda said, reduced tumor lysis syndrome (TLS) risk, shifting 90% of patients with high baseline TLS risk to medium or low-risk categories (from 77 to 51 patients), precluding need for hospitalization with venetoclax initiation.

The rate for best response of uMRD (defined as uMRD over at least 3 cycles in both peripheral blood and bone marrow) in evaluable patients was 75% in peripheral blood (n = 163) and 72% in bone marrow (n = 155).

Confirmed uMRD was achieved in 86/149 (58%), with uMRD not confirmed in 63/149 (uMRD 32% in bone marrow and 48% in peripheral blood). One-year DFS after the further randomization to placebo or ibrutinib in the confirmed uMRD group was 95.3% in the placebo group and 100% in the ibrutinib group (P = .1475). In the uMRD not confirmed group, 30-month progression-free survival (PFS) was 95.2% and 96.7% in the ibrutinib and ibrutinib plus venetoclax groups, respectively. Thirty-month PFS rates in the confirmed uMRD placebo and ibrutinib arms were 95.3% and 100%. “Thirty-month PFS rates were greater than 95% across all randomized arms,” Dr. Wierda stated.

In patients without confirmed uMRD after 12 cycles of combined ibrutinib plus venetoclax, additional randomized treatment led to greater increases in uMRD in the ibrutinib plus venetoclax group than in the ibrutinib alone group (bone marrow additional 10% ibrutinib alone, 34% ibrutinib plus venetoclax; peripheral blood 0% ibrutinib, 19% ibrutinib plus venetoclax).

Adverse events generally decreased after the first 6 months of ibrutinib plus venetoclax treatment, with no new safety signals emerging over time. “There were no safety concerns with this highly active combination of first-line ibrutinib plus venetoclax. It’s an oral, once-daily fixed duration regimen that achieves undetectable MRD in blood or bone marrow in three-fourths of patients after 12 cycles of combined treatment.”

When asked, in a question-and-answer session after his presentation, if the findings were “practice changing,” Dr. Wierda responded: “We need additional data from ongoing studies looking at various combinations of targeted therapy. But this study does clearly show efficacy in terms of depth of remission, and it supports the concept of fixed duration treatment, particularly for those patients who achieved undetectable MRD status.”
 

SOURCE: William G. Wierda, MD, PhD. ASH 2020, Abstract 123.

Among chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients in the minimal residual disease (MRD) cohort of the phase 2 CAPTIVATE trial, a 1-year disease-free survival (DFS) rate of 95% in those randomized to placebo after 12 cycles of combined ibrutinib plus venetoclax supports a fixed-duration treatment approach, according to William G. Wierda, MD, PhD, University of Texas, MD Anderson Cancer Center, Houston.

Ibrutinib, a once-daily Bruton kinase inhibitor, is the only targeted therapy for first-line treatment of CLL that has demonstrated significant overall survival benefit in randomized phase 3 studies, Dr. Wierda said at the American Society of Hematology annual meeting, held virtually.

Ibrutinib and venetoclax have synergistic and complementary antitumor activity, he noted, through mobilizing and clearing CLL cells from protective niches and disease compartments beyond blood and bone marrow.

Fixed-duration study

CAPTIVATE (PCYC-1142), an international phase 2 study, evaluated first-line treatment with 12 cycles of the ibrutinib/venetoclax combination in MRD and fixed-duration cohorts. The current primary analysis of 1-year DFS from the MRD cohort tested whether the regimen allows for treatment-free remission in the setting of confirmed undetectable MRD (uMRD).

Patients (n = 164, median age 58 years) in the CAPTIVATE study MRD cohort had previously untreated active CLL/SLL requiring treatment per International Workshop on Chronic Lymphocytic Leukemia criteria.

They received 3 cycles of lead-in ibrutinib (420 mg once daily) followed by 12 cycles of ibrutinib (420 mg once daily plus venetoclax ramp-up to 400 mg once daily). Thereafter, in an MRD-guided 1:1 randomization stratified by immunoglobulin heavy chain (IGHV) mutational status, those with confirmed uMRD received either placebo or ibrutinib, and those with uMRD not confirmed received either ibrutinib or ibrutinib plus venetoclax (both open-label).

Among high-risk features in CAPTIVATE subjects, 60% of patients had unmutated IGHV, with del(17p)/TP53 mutation in 20%, del(11Q) in 17%, complex karyotype in 19%, cytopenias in 36%, bulky lymph nodes in 32%, and absolute neutrophil count ≥25x109/L in 76%.
 

Response findings

The ibrutinib lead-in, Dr. Wierda said, reduced tumor lysis syndrome (TLS) risk, shifting 90% of patients with high baseline TLS risk to medium or low-risk categories (from 77 to 51 patients), precluding need for hospitalization with venetoclax initiation.

The rate for best response of uMRD (defined as uMRD over at least 3 cycles in both peripheral blood and bone marrow) in evaluable patients was 75% in peripheral blood (n = 163) and 72% in bone marrow (n = 155).

Confirmed uMRD was achieved in 86/149 (58%), with uMRD not confirmed in 63/149 (uMRD 32% in bone marrow and 48% in peripheral blood). One-year DFS after the further randomization to placebo or ibrutinib in the confirmed uMRD group was 95.3% in the placebo group and 100% in the ibrutinib group (P = .1475). In the uMRD not confirmed group, 30-month progression-free survival (PFS) was 95.2% and 96.7% in the ibrutinib and ibrutinib plus venetoclax groups, respectively. Thirty-month PFS rates in the confirmed uMRD placebo and ibrutinib arms were 95.3% and 100%. “Thirty-month PFS rates were greater than 95% across all randomized arms,” Dr. Wierda stated.

In patients without confirmed uMRD after 12 cycles of combined ibrutinib plus venetoclax, additional randomized treatment led to greater increases in uMRD in the ibrutinib plus venetoclax group than in the ibrutinib alone group (bone marrow additional 10% ibrutinib alone, 34% ibrutinib plus venetoclax; peripheral blood 0% ibrutinib, 19% ibrutinib plus venetoclax).

Adverse events generally decreased after the first 6 months of ibrutinib plus venetoclax treatment, with no new safety signals emerging over time. “There were no safety concerns with this highly active combination of first-line ibrutinib plus venetoclax. It’s an oral, once-daily fixed duration regimen that achieves undetectable MRD in blood or bone marrow in three-fourths of patients after 12 cycles of combined treatment.”

When asked, in a question-and-answer session after his presentation, if the findings were “practice changing,” Dr. Wierda responded: “We need additional data from ongoing studies looking at various combinations of targeted therapy. But this study does clearly show efficacy in terms of depth of remission, and it supports the concept of fixed duration treatment, particularly for those patients who achieved undetectable MRD status.”
 

SOURCE: William G. Wierda, MD, PhD. ASH 2020, Abstract 123.

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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

New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).

In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.  

The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.

Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.

“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.

“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.

Several experts in addition to the authors hailed the study as practice changing.

Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.

“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”

Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.

“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.

Immediate impact on clinical practice

Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.

Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.

“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.

“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.

Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.

He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
 

Reimbursement by CMS for Medicare recipients

Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.

“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.

Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.

“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.

“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.

The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
 

BMT CTN 1102 study details

Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.

The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.

Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.

Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.

The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.

At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.

Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.

In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).

In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.

Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.

Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
 

Role for alternate donors

Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.

However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.

“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.

Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”

“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”

Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.

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