Myelodysplastic Syndrome

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Key clinical point: Information of the flow cytometry immunophenotyping (FCI) data during therapy combined with the hematological response can help physicians identify patients with myelodysplastic syndrome (MDS) with a higher probability of maintaining a good quality of response to 5-azacitidine (AZA) therapy for a longer period of time.

Major finding: After a median of 6 cycles of AZA, an FCI improvement was found in 41% of patients, and this finding correlated with a better clinical response (P less than .001). FCI improvement correlated with hematological improvement (HI), and the probability of maintaining a clinical response at 12 cycles of AZA was twice as large (67%) for those who achieved an HI and an FCI improvement after 6 cycles of AZA compared with patients who only achieved an HI (33%).

Study details: The data come from a study of 81 patients diagnosed with MDS in 5 European centers.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Subirá D et al. Ann Hematol. 2021 Jan 9. doi: 10.1007/s00277-021-04411-4.

Key clinical point: Information of the flow cytometry immunophenotyping (FCI) data during therapy combined with the hematological response can help physicians identify patients with myelodysplastic syndrome (MDS) with a higher probability of maintaining a good quality of response to 5-azacitidine (AZA) therapy for a longer period of time.

Major finding: After a median of 6 cycles of AZA, an FCI improvement was found in 41% of patients, and this finding correlated with a better clinical response (P less than .001). FCI improvement correlated with hematological improvement (HI), and the probability of maintaining a clinical response at 12 cycles of AZA was twice as large (67%) for those who achieved an HI and an FCI improvement after 6 cycles of AZA compared with patients who only achieved an HI (33%).

Study details: The data come from a study of 81 patients diagnosed with MDS in 5 European centers.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Subirá D et al. Ann Hematol. 2021 Jan 9. doi: 10.1007/s00277-021-04411-4.

Key clinical point: Information of the flow cytometry immunophenotyping (FCI) data during therapy combined with the hematological response can help physicians identify patients with myelodysplastic syndrome (MDS) with a higher probability of maintaining a good quality of response to 5-azacitidine (AZA) therapy for a longer period of time.

Major finding: After a median of 6 cycles of AZA, an FCI improvement was found in 41% of patients, and this finding correlated with a better clinical response (P less than .001). FCI improvement correlated with hematological improvement (HI), and the probability of maintaining a clinical response at 12 cycles of AZA was twice as large (67%) for those who achieved an HI and an FCI improvement after 6 cycles of AZA compared with patients who only achieved an HI (33%).

Study details: The data come from a study of 81 patients diagnosed with MDS in 5 European centers.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Subirá D et al. Ann Hematol. 2021 Jan 9. doi: 10.1007/s00277-021-04411-4.

Key clinical point: Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) and azacitidine appears tolerable when given over 5 days and has encouraging response rates in patients with myelodysplastic syndromes (MDS).

Major finding: Two complete responses and 6 marrow responses were seen for an overall response rate (ORR) of 36% in evaluable patients. The ORR for patients receiving plerixafor (any dose), G-CSF, and azacitidine was 53%. Blast mobilization during treatment correlated with response, with patients that mobilized greater than 2-fold having an ORR of 60% vs. 17% for those that did not (P = .035).

Study details: The data come from an open-label, phase 1 study of 28 MDS patients treated with plerixafor, G-CSF, and azacitidine with a standard 3 + 3 design with 3 dose escalation cohorts of plerixafor 320 mg/kg/day, 440 mg/kg/day, and 560 mg/kg/day.

Disclosures: The study was supported by the American Society of Hematology Clinical Research Training Institute. Four of the authors reported receiving honoraria from Sanofi and 1 received honoraria from Bristol Myers Squibb.

Source: Huselton E et al. Leuk Lymphoma. 2021 Jan 19. doi: 10.1080/10428194.2021.

Key clinical point: Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) and azacitidine appears tolerable when given over 5 days and has encouraging response rates in patients with myelodysplastic syndromes (MDS).

Major finding: Two complete responses and 6 marrow responses were seen for an overall response rate (ORR) of 36% in evaluable patients. The ORR for patients receiving plerixafor (any dose), G-CSF, and azacitidine was 53%. Blast mobilization during treatment correlated with response, with patients that mobilized greater than 2-fold having an ORR of 60% vs. 17% for those that did not (P = .035).

Study details: The data come from an open-label, phase 1 study of 28 MDS patients treated with plerixafor, G-CSF, and azacitidine with a standard 3 + 3 design with 3 dose escalation cohorts of plerixafor 320 mg/kg/day, 440 mg/kg/day, and 560 mg/kg/day.

Disclosures: The study was supported by the American Society of Hematology Clinical Research Training Institute. Four of the authors reported receiving honoraria from Sanofi and 1 received honoraria from Bristol Myers Squibb.

Source: Huselton E et al. Leuk Lymphoma. 2021 Jan 19. doi: 10.1080/10428194.2021.

Key clinical point: Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) and azacitidine appears tolerable when given over 5 days and has encouraging response rates in patients with myelodysplastic syndromes (MDS).

Major finding: Two complete responses and 6 marrow responses were seen for an overall response rate (ORR) of 36% in evaluable patients. The ORR for patients receiving plerixafor (any dose), G-CSF, and azacitidine was 53%. Blast mobilization during treatment correlated with response, with patients that mobilized greater than 2-fold having an ORR of 60% vs. 17% for those that did not (P = .035).

Study details: The data come from an open-label, phase 1 study of 28 MDS patients treated with plerixafor, G-CSF, and azacitidine with a standard 3 + 3 design with 3 dose escalation cohorts of plerixafor 320 mg/kg/day, 440 mg/kg/day, and 560 mg/kg/day.

Disclosures: The study was supported by the American Society of Hematology Clinical Research Training Institute. Four of the authors reported receiving honoraria from Sanofi and 1 received honoraria from Bristol Myers Squibb.

Source: Huselton E et al. Leuk Lymphoma. 2021 Jan 19. doi: 10.1080/10428194.2021.

Key clinical point: The addition of lenalidomide (LEN) to epoetin (EPO) alfa offers a superior probability of clinically meaningful and highly durable erythroid response vs. LEN alone in patients with lower-risk, non-del (5q) myelodysplastic syndromes (MDS) who have anemia that is refractory to recombinant erythropoietin.

Major finding: After 4 cycles of treatment, major erythroid response was significantly higher with the combination of LEN and erythropoietin vs. LEN alone (28.3% vs. 11.5%; P = .004). Responses to the combined treatment were highly durable with a median major erythroid response duration of 23.8 months in the combined therapy cohort vs. 13 months in the LEN cohort.

Study details: In this phase 3 US intergroup trial, 195 patients with MDS and anemia were randomly assigned to receive LEN and EPO alfa (n = 99) or LEN alone (n = 96) following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

Disclosures: The study was supported by the ECOG-ACRIN Cancer Research Group Study, the National Cancer Institute (NCI) of the National Institutes of Health, and NCI. The authors reported ties with various pharmaceutical companies.

Source: List AF et al. J Clin Oncol. 2021 Jan 13. doi: 10.1200/JCO.20.01691.

Key clinical point: The addition of lenalidomide (LEN) to epoetin (EPO) alfa offers a superior probability of clinically meaningful and highly durable erythroid response vs. LEN alone in patients with lower-risk, non-del (5q) myelodysplastic syndromes (MDS) who have anemia that is refractory to recombinant erythropoietin.

Major finding: After 4 cycles of treatment, major erythroid response was significantly higher with the combination of LEN and erythropoietin vs. LEN alone (28.3% vs. 11.5%; P = .004). Responses to the combined treatment were highly durable with a median major erythroid response duration of 23.8 months in the combined therapy cohort vs. 13 months in the LEN cohort.

Study details: In this phase 3 US intergroup trial, 195 patients with MDS and anemia were randomly assigned to receive LEN and EPO alfa (n = 99) or LEN alone (n = 96) following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

Disclosures: The study was supported by the ECOG-ACRIN Cancer Research Group Study, the National Cancer Institute (NCI) of the National Institutes of Health, and NCI. The authors reported ties with various pharmaceutical companies.

Source: List AF et al. J Clin Oncol. 2021 Jan 13. doi: 10.1200/JCO.20.01691.

Key clinical point: The addition of lenalidomide (LEN) to epoetin (EPO) alfa offers a superior probability of clinically meaningful and highly durable erythroid response vs. LEN alone in patients with lower-risk, non-del (5q) myelodysplastic syndromes (MDS) who have anemia that is refractory to recombinant erythropoietin.

Major finding: After 4 cycles of treatment, major erythroid response was significantly higher with the combination of LEN and erythropoietin vs. LEN alone (28.3% vs. 11.5%; P = .004). Responses to the combined treatment were highly durable with a median major erythroid response duration of 23.8 months in the combined therapy cohort vs. 13 months in the LEN cohort.

Study details: In this phase 3 US intergroup trial, 195 patients with MDS and anemia were randomly assigned to receive LEN and EPO alfa (n = 99) or LEN alone (n = 96) following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

Disclosures: The study was supported by the ECOG-ACRIN Cancer Research Group Study, the National Cancer Institute (NCI) of the National Institutes of Health, and NCI. The authors reported ties with various pharmaceutical companies.

Source: List AF et al. J Clin Oncol. 2021 Jan 13. doi: 10.1200/JCO.20.01691.

Key clinical point: This study found no evidence of an association between nonsteroidal anti-inflammatory drug (NSAID) use and myelodysplastic syndromes (MDS).

Major finding: No significant association was seen between MDS and use of any NSAID (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.68-1.23), aspirin (aOR, 0.87; 95% CI, 0.67-1.14), ibuprofen (aOR, 0.91; 95% CI, 0.64-1.30), or acetaminophen (aOR, 1.29; 95% CI, 0.90-1.84). No association was observed in analyses stratified by sex; however, the direction of the effect between NSAID use and MDS varied by MDS subtype.

Study details: This population-based case-control study included 399 MDS cases and 698 controls using data from the Adults in Minnesota with Myelodysplastic Syndromes Study.

Disclosures: The study was funded by a National Institutes of Health grant. The authors declared no conflicts of interest.

Source: Hubbard AK et al. Leuk Lymphoma. 2021 Jan 8. doi: 10.1080/10428194.2020.

Key clinical point: This study found no evidence of an association between nonsteroidal anti-inflammatory drug (NSAID) use and myelodysplastic syndromes (MDS).

Major finding: No significant association was seen between MDS and use of any NSAID (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.68-1.23), aspirin (aOR, 0.87; 95% CI, 0.67-1.14), ibuprofen (aOR, 0.91; 95% CI, 0.64-1.30), or acetaminophen (aOR, 1.29; 95% CI, 0.90-1.84). No association was observed in analyses stratified by sex; however, the direction of the effect between NSAID use and MDS varied by MDS subtype.

Study details: This population-based case-control study included 399 MDS cases and 698 controls using data from the Adults in Minnesota with Myelodysplastic Syndromes Study.

Disclosures: The study was funded by a National Institutes of Health grant. The authors declared no conflicts of interest.

Source: Hubbard AK et al. Leuk Lymphoma. 2021 Jan 8. doi: 10.1080/10428194.2020.

Key clinical point: This study found no evidence of an association between nonsteroidal anti-inflammatory drug (NSAID) use and myelodysplastic syndromes (MDS).

Major finding: No significant association was seen between MDS and use of any NSAID (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.68-1.23), aspirin (aOR, 0.87; 95% CI, 0.67-1.14), ibuprofen (aOR, 0.91; 95% CI, 0.64-1.30), or acetaminophen (aOR, 1.29; 95% CI, 0.90-1.84). No association was observed in analyses stratified by sex; however, the direction of the effect between NSAID use and MDS varied by MDS subtype.

Study details: This population-based case-control study included 399 MDS cases and 698 controls using data from the Adults in Minnesota with Myelodysplastic Syndromes Study.

Disclosures: The study was funded by a National Institutes of Health grant. The authors declared no conflicts of interest.

Source: Hubbard AK et al. Leuk Lymphoma. 2021 Jan 8. doi: 10.1080/10428194.2020.

Key clinical point: A study found smoking, history of autoimmune disease and benzene exposure to significant risk factors for de novo myelodysplastic syndromes (MDS). These factors also had a similar yet non-significant association with therapy-related MDS (tMDS).

Major finding:  After adjusting for confounders, former smoking status (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.10-1.93), history of autoimmune disease (OR, 1.34; 95% CI, 0.99-1.82) and benzene exposure (OR, 1.48; 95% CI, 1.00-2.19) were significantly associated with de novo MDS. The risk estimates for these associations were similar in magnitude for tMDS, but non-significant.

Study details: The data come from a case-control study involving 346 de novo MDS cases, 37 tMDS cases and 682 controls matched by age and sex.

Disclosures: The study was funded by the National Institutes of Health. The authors declared no conflicts of interest.

Source: Yarosh R et al. Cancer Causes Control. 2021 Jan 4. doi: 10.1007/s10552-020-01378-x.

Key clinical point: A study found smoking, history of autoimmune disease and benzene exposure to significant risk factors for de novo myelodysplastic syndromes (MDS). These factors also had a similar yet non-significant association with therapy-related MDS (tMDS).

Major finding:  After adjusting for confounders, former smoking status (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.10-1.93), history of autoimmune disease (OR, 1.34; 95% CI, 0.99-1.82) and benzene exposure (OR, 1.48; 95% CI, 1.00-2.19) were significantly associated with de novo MDS. The risk estimates for these associations were similar in magnitude for tMDS, but non-significant.

Study details: The data come from a case-control study involving 346 de novo MDS cases, 37 tMDS cases and 682 controls matched by age and sex.

Disclosures: The study was funded by the National Institutes of Health. The authors declared no conflicts of interest.

Source: Yarosh R et al. Cancer Causes Control. 2021 Jan 4. doi: 10.1007/s10552-020-01378-x.

Key clinical point: A study found smoking, history of autoimmune disease and benzene exposure to significant risk factors for de novo myelodysplastic syndromes (MDS). These factors also had a similar yet non-significant association with therapy-related MDS (tMDS).

Major finding:  After adjusting for confounders, former smoking status (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.10-1.93), history of autoimmune disease (OR, 1.34; 95% CI, 0.99-1.82) and benzene exposure (OR, 1.48; 95% CI, 1.00-2.19) were significantly associated with de novo MDS. The risk estimates for these associations were similar in magnitude for tMDS, but non-significant.

Study details: The data come from a case-control study involving 346 de novo MDS cases, 37 tMDS cases and 682 controls matched by age and sex.

Disclosures: The study was funded by the National Institutes of Health. The authors declared no conflicts of interest.

Source: Yarosh R et al. Cancer Causes Control. 2021 Jan 4. doi: 10.1007/s10552-020-01378-x.

Key clinical point: Myelodysplastic syndrome (MDS) patients treated with hypomethylating agents (HMA), especially those with higher-risk MDS have unmet clinical needs in real-world setting.

Major finding: Median survival was 11.6 months, 18.4 months, and 19.1 months for the higher-risk, intermediate-risk, and unknown-risk groups, respectively. Corresponding median time-to-AML transformation for the 3 groups were 19.3 months, 50.4 months, and 'not reached', respectively.

Study details: The data come from 3,046 MDS patients treated with HMA from the SEER-Medicare database. The patients were categorized as higher-risk, intermediate-risk, and unknown-risk.

Disclosures: The study was sponsored by Novartis. I Sadek and X Cao are employees and stockholders of Novartis.  G Bonifacio was an employee and stockholder of Novartis at the time of the study. EM Stein provided paid consulting services to Novartis. D Latremouille-Viau, S Shi, A Guerin, and EQ Wu are employees of Analysis Group, Inc. which provided paid consulting services to Novartis.

Source: Stein EM et al. Leuk Lymphoma. 2021 Jan 11. doi: 10.1080/10428194.2020.1869959.

Key clinical point: Myelodysplastic syndrome (MDS) patients treated with hypomethylating agents (HMA), especially those with higher-risk MDS have unmet clinical needs in real-world setting.

Major finding: Median survival was 11.6 months, 18.4 months, and 19.1 months for the higher-risk, intermediate-risk, and unknown-risk groups, respectively. Corresponding median time-to-AML transformation for the 3 groups were 19.3 months, 50.4 months, and 'not reached', respectively.

Study details: The data come from 3,046 MDS patients treated with HMA from the SEER-Medicare database. The patients were categorized as higher-risk, intermediate-risk, and unknown-risk.

Disclosures: The study was sponsored by Novartis. I Sadek and X Cao are employees and stockholders of Novartis.  G Bonifacio was an employee and stockholder of Novartis at the time of the study. EM Stein provided paid consulting services to Novartis. D Latremouille-Viau, S Shi, A Guerin, and EQ Wu are employees of Analysis Group, Inc. which provided paid consulting services to Novartis.

Source: Stein EM et al. Leuk Lymphoma. 2021 Jan 11. doi: 10.1080/10428194.2020.1869959.

Key clinical point: Myelodysplastic syndrome (MDS) patients treated with hypomethylating agents (HMA), especially those with higher-risk MDS have unmet clinical needs in real-world setting.

Major finding: Median survival was 11.6 months, 18.4 months, and 19.1 months for the higher-risk, intermediate-risk, and unknown-risk groups, respectively. Corresponding median time-to-AML transformation for the 3 groups were 19.3 months, 50.4 months, and 'not reached', respectively.

Study details: The data come from 3,046 MDS patients treated with HMA from the SEER-Medicare database. The patients were categorized as higher-risk, intermediate-risk, and unknown-risk.

Disclosures: The study was sponsored by Novartis. I Sadek and X Cao are employees and stockholders of Novartis.  G Bonifacio was an employee and stockholder of Novartis at the time of the study. EM Stein provided paid consulting services to Novartis. D Latremouille-Viau, S Shi, A Guerin, and EQ Wu are employees of Analysis Group, Inc. which provided paid consulting services to Novartis.

Source: Stein EM et al. Leuk Lymphoma. 2021 Jan 11. doi: 10.1080/10428194.2020.1869959.

Key clinical point: Preliminary data of a phase 2 study found that the combination of azacitidine and pembrolizumab was well-tolerated and demonstrated antitumor activity in treatment-naïve patients with higher-Risk myelodysplastic syndrome (MDS)

Major finding: The overall response rate was 80%, with 3 patients reaching complete remission, 4 patients achieving marrow CR (mCR), 4 patients achieving mCR with hematologic improvement (HI), and 1 patient demonstrating HI. Treatment was well-tolerated, the most common treatment-related adverse events being arthralgia, pneumonia, nausea, and skin rash.

Study details: The preliminary phase 2 trial data come from 17 treatment-naïve patients treated with frontline combination of azacitidine and pembrolizumab, with a median follow-up time of 13.8 months and 5 patients continuing on treatment in cycles 4-28.

Disclosures: The study is sponsored by M.D. Anderson Cancer Center. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Chien KS et al. ASH 2020. 2020 Dec 5. Abstract 1288.

Key clinical point: Preliminary data of a phase 2 study found that the combination of azacitidine and pembrolizumab was well-tolerated and demonstrated antitumor activity in treatment-naïve patients with higher-Risk myelodysplastic syndrome (MDS)

Major finding: The overall response rate was 80%, with 3 patients reaching complete remission, 4 patients achieving marrow CR (mCR), 4 patients achieving mCR with hematologic improvement (HI), and 1 patient demonstrating HI. Treatment was well-tolerated, the most common treatment-related adverse events being arthralgia, pneumonia, nausea, and skin rash.

Study details: The preliminary phase 2 trial data come from 17 treatment-naïve patients treated with frontline combination of azacitidine and pembrolizumab, with a median follow-up time of 13.8 months and 5 patients continuing on treatment in cycles 4-28.

Disclosures: The study is sponsored by M.D. Anderson Cancer Center. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Chien KS et al. ASH 2020. 2020 Dec 5. Abstract 1288.

Key clinical point: Preliminary data of a phase 2 study found that the combination of azacitidine and pembrolizumab was well-tolerated and demonstrated antitumor activity in treatment-naïve patients with higher-Risk myelodysplastic syndrome (MDS)

Major finding: The overall response rate was 80%, with 3 patients reaching complete remission, 4 patients achieving marrow CR (mCR), 4 patients achieving mCR with hematologic improvement (HI), and 1 patient demonstrating HI. Treatment was well-tolerated, the most common treatment-related adverse events being arthralgia, pneumonia, nausea, and skin rash.

Study details: The preliminary phase 2 trial data come from 17 treatment-naïve patients treated with frontline combination of azacitidine and pembrolizumab, with a median follow-up time of 13.8 months and 5 patients continuing on treatment in cycles 4-28.

Disclosures: The study is sponsored by M.D. Anderson Cancer Center. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Chien KS et al. ASH 2020. 2020 Dec 5. Abstract 1288.

Key clinical point: Older patients with advanced myelodysplastic syndrome (MDS) may benefit from allogeneic hematopoietic cell transplantation (HCT), which is usually reserved for younger patients.

Major finding: At 3 years, the donor vs no-donor group had a greater improvement in overall survival (absolute difference, 21.3%; P = .0001) and higher leukemia-free survival (35.8% vs 20.6%; P = .003).

Study details: The study included patients aged 50-75 years with newly diagnosed MDS of higher risk and who were eligible for reduced-intensity conditioning (RIC) allogeneic HCT. Patients were initially assigned to the "no-donor" group at enrollment and reassigned to the donor group when a suitable donor was identified.

Disclosures: No specific funding information was available for the study. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Nakamura R et al. ASH 2020. 2020 Dec 5. Abstract 75.

Key clinical point: Older patients with advanced myelodysplastic syndrome (MDS) may benefit from allogeneic hematopoietic cell transplantation (HCT), which is usually reserved for younger patients.

Major finding: At 3 years, the donor vs no-donor group had a greater improvement in overall survival (absolute difference, 21.3%; P = .0001) and higher leukemia-free survival (35.8% vs 20.6%; P = .003).

Study details: The study included patients aged 50-75 years with newly diagnosed MDS of higher risk and who were eligible for reduced-intensity conditioning (RIC) allogeneic HCT. Patients were initially assigned to the "no-donor" group at enrollment and reassigned to the donor group when a suitable donor was identified.

Disclosures: No specific funding information was available for the study. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Nakamura R et al. ASH 2020. 2020 Dec 5. Abstract 75.

Key clinical point: Older patients with advanced myelodysplastic syndrome (MDS) may benefit from allogeneic hematopoietic cell transplantation (HCT), which is usually reserved for younger patients.

Major finding: At 3 years, the donor vs no-donor group had a greater improvement in overall survival (absolute difference, 21.3%; P = .0001) and higher leukemia-free survival (35.8% vs 20.6%; P = .003).

Study details: The study included patients aged 50-75 years with newly diagnosed MDS of higher risk and who were eligible for reduced-intensity conditioning (RIC) allogeneic HCT. Patients were initially assigned to the "no-donor" group at enrollment and reassigned to the donor group when a suitable donor was identified.

Disclosures: No specific funding information was available for the study. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Nakamura R et al. ASH 2020. 2020 Dec 5. Abstract 75.

Key clinical point: Poly (ADP-ribose) polymerase (PARP) inhibitors were associated with an increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Major finding: Meta-analysis of 18 placebo randomized clinical trials (n=7,307) revealed an increased risk for MDS and AML with PARP inhibitors vs. placebo (Peto odds ratio, 2.63; P = .026). The incidence of MDS and AML across PARP inhibitor groups was 0.73% vs. 0.47% for placebo groups. In VigiBase, median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Of 104 cases of MDS/AML that reported outcomes, 45% of cases resulted in death.

Study details: This study estimated the risk of MDS and AML related to PARP inhibitors, via a systematic review and safety meta-analysis, and described clinical features of PARP inhibitor-related MDS (n = 99) and AML (n = 79) cases reported in VigiBase, the WHO’s pharmacovigilance database.

Disclosures: The study did not receive any funding. Some study investigators reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

Source: Morice PM et al. Lancet Haematol. 2020 Dec 18. doi: 10.1016/S2352-3026(20)30360-4.

Key clinical point: Poly (ADP-ribose) polymerase (PARP) inhibitors were associated with an increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Major finding: Meta-analysis of 18 placebo randomized clinical trials (n=7,307) revealed an increased risk for MDS and AML with PARP inhibitors vs. placebo (Peto odds ratio, 2.63; P = .026). The incidence of MDS and AML across PARP inhibitor groups was 0.73% vs. 0.47% for placebo groups. In VigiBase, median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Of 104 cases of MDS/AML that reported outcomes, 45% of cases resulted in death.

Study details: This study estimated the risk of MDS and AML related to PARP inhibitors, via a systematic review and safety meta-analysis, and described clinical features of PARP inhibitor-related MDS (n = 99) and AML (n = 79) cases reported in VigiBase, the WHO’s pharmacovigilance database.

Disclosures: The study did not receive any funding. Some study investigators reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

Source: Morice PM et al. Lancet Haematol. 2020 Dec 18. doi: 10.1016/S2352-3026(20)30360-4.

Key clinical point: Poly (ADP-ribose) polymerase (PARP) inhibitors were associated with an increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Major finding: Meta-analysis of 18 placebo randomized clinical trials (n=7,307) revealed an increased risk for MDS and AML with PARP inhibitors vs. placebo (Peto odds ratio, 2.63; P = .026). The incidence of MDS and AML across PARP inhibitor groups was 0.73% vs. 0.47% for placebo groups. In VigiBase, median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Of 104 cases of MDS/AML that reported outcomes, 45% of cases resulted in death.

Study details: This study estimated the risk of MDS and AML related to PARP inhibitors, via a systematic review and safety meta-analysis, and described clinical features of PARP inhibitor-related MDS (n = 99) and AML (n = 79) cases reported in VigiBase, the WHO’s pharmacovigilance database.

Disclosures: The study did not receive any funding. Some study investigators reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

Source: Morice PM et al. Lancet Haematol. 2020 Dec 18. doi: 10.1016/S2352-3026(20)30360-4.