User login
Ibrutinib linked to invasive fungal infections
The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.
French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.
“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.
Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.
Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.
They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.
Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.
The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.
Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.
SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.
The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.
French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.
“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.
Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.
Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.
They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.
Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.
The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.
Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.
SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.
The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.
French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.
“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.
Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.
Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.
They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.
Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.
The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.
Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.
SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.
FROM BLOOD
Key clinical point:
Major finding: Of 33 identified cases, 27 were invasive aspergillosis.
Study details: Retrospective review of case reports from 16 French centers.
Disclosures: Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees with the company. All other authors declared no competing financial interests.
Source: Ghez D et al. Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.
Baseline stress signals need for psychological help in CLL
, according to a prospective study of 152 patients.
“These findings suggest that integration of psychological intervention for patients who have high cancer-specific stress at baseline might be appropriate for this population,” wrote investigators led by Neha G. Goyal, PhD, a research fellow at Wake Forest University, Winston-Salem, N.C.
The subjects all had relapsed/refractory chronic lymphocytic leukemia (CLL). They filled out mental and physical function questionnaires at baseline, then at months 1, 2, and 5 during a nonrandomized phase 2 trial of ibrutinib (Imbruvica). The findings were published in the Annals of Behavioral Medicine.
Cancer-specific stress – essentially traumatic stress associated with cancer diagnosis, recurrence, and treatment – was assessed by the Impact of Event Scale, a common cancer research tool in which patients rate the intensity of intrusive thoughts and avoidant thoughts and behaviors. A score of 8 – out of a range of 0-64 – was the cut point used to separate patients with low versus high stress; higher scores mean worse symptoms.
“At treatment initiation, cancer-specific stress was associated with higher levels of cognitive-affective depressive symptoms, negative mood, fatigue interference, and sleep problems, and lower mental health quality of life. While patients with higher cancer-specific stress at baseline improved more rapidly on these outcomes ... higher cancer-specific stress at baseline was still associated with poorer psychological outcomes, but not physical outcomes, at 5 months,” the investigators said (Ann Behav Med. 2018 Feb 9. doi: 10.1093/abm/kax004).
For instance, high-stress patients started the trial with mean scores of about 4.5 on the 42-point cognitive-affective subscale of the Beck Depression Inventory; scores improved to about 2.5 after 5 months of treatment. Low-stress patients, however, started and ended the study with scores of about 1.5.
Cancer-specific stress has been associated with poorer outcomes in previous cancer studies, but its impact on CLL hasn’t been clear until now. It might be a particularly bad problem in CLL, because the disease is incurable and patients go through multiple relapses and treatment cycles.
“There has been a call to screen cancer patients to determine those who may be at risk for poor outcomes, and assessment of cancer-specific stress may have clinical utility as an individual difference predictor of psychological responses,” the team noted.
The mean age in the study was 64.1 years; 71% of the subjects were men. The majority were educated beyond high school, and almost all reported significant, supportive relationships. Patients had a median of three prior therapies, but one patients had been through 16.
Dr. Goyal reported having no financial disclosures. One author disclosed ties to Pharmacyclics and Janssen, marketers of ibrutinib. The work was supported by the National Cancer Institute and Pharmacyclics, among others.
, according to a prospective study of 152 patients.
“These findings suggest that integration of psychological intervention for patients who have high cancer-specific stress at baseline might be appropriate for this population,” wrote investigators led by Neha G. Goyal, PhD, a research fellow at Wake Forest University, Winston-Salem, N.C.
The subjects all had relapsed/refractory chronic lymphocytic leukemia (CLL). They filled out mental and physical function questionnaires at baseline, then at months 1, 2, and 5 during a nonrandomized phase 2 trial of ibrutinib (Imbruvica). The findings were published in the Annals of Behavioral Medicine.
Cancer-specific stress – essentially traumatic stress associated with cancer diagnosis, recurrence, and treatment – was assessed by the Impact of Event Scale, a common cancer research tool in which patients rate the intensity of intrusive thoughts and avoidant thoughts and behaviors. A score of 8 – out of a range of 0-64 – was the cut point used to separate patients with low versus high stress; higher scores mean worse symptoms.
“At treatment initiation, cancer-specific stress was associated with higher levels of cognitive-affective depressive symptoms, negative mood, fatigue interference, and sleep problems, and lower mental health quality of life. While patients with higher cancer-specific stress at baseline improved more rapidly on these outcomes ... higher cancer-specific stress at baseline was still associated with poorer psychological outcomes, but not physical outcomes, at 5 months,” the investigators said (Ann Behav Med. 2018 Feb 9. doi: 10.1093/abm/kax004).
For instance, high-stress patients started the trial with mean scores of about 4.5 on the 42-point cognitive-affective subscale of the Beck Depression Inventory; scores improved to about 2.5 after 5 months of treatment. Low-stress patients, however, started and ended the study with scores of about 1.5.
Cancer-specific stress has been associated with poorer outcomes in previous cancer studies, but its impact on CLL hasn’t been clear until now. It might be a particularly bad problem in CLL, because the disease is incurable and patients go through multiple relapses and treatment cycles.
“There has been a call to screen cancer patients to determine those who may be at risk for poor outcomes, and assessment of cancer-specific stress may have clinical utility as an individual difference predictor of psychological responses,” the team noted.
The mean age in the study was 64.1 years; 71% of the subjects were men. The majority were educated beyond high school, and almost all reported significant, supportive relationships. Patients had a median of three prior therapies, but one patients had been through 16.
Dr. Goyal reported having no financial disclosures. One author disclosed ties to Pharmacyclics and Janssen, marketers of ibrutinib. The work was supported by the National Cancer Institute and Pharmacyclics, among others.
, according to a prospective study of 152 patients.
“These findings suggest that integration of psychological intervention for patients who have high cancer-specific stress at baseline might be appropriate for this population,” wrote investigators led by Neha G. Goyal, PhD, a research fellow at Wake Forest University, Winston-Salem, N.C.
The subjects all had relapsed/refractory chronic lymphocytic leukemia (CLL). They filled out mental and physical function questionnaires at baseline, then at months 1, 2, and 5 during a nonrandomized phase 2 trial of ibrutinib (Imbruvica). The findings were published in the Annals of Behavioral Medicine.
Cancer-specific stress – essentially traumatic stress associated with cancer diagnosis, recurrence, and treatment – was assessed by the Impact of Event Scale, a common cancer research tool in which patients rate the intensity of intrusive thoughts and avoidant thoughts and behaviors. A score of 8 – out of a range of 0-64 – was the cut point used to separate patients with low versus high stress; higher scores mean worse symptoms.
“At treatment initiation, cancer-specific stress was associated with higher levels of cognitive-affective depressive symptoms, negative mood, fatigue interference, and sleep problems, and lower mental health quality of life. While patients with higher cancer-specific stress at baseline improved more rapidly on these outcomes ... higher cancer-specific stress at baseline was still associated with poorer psychological outcomes, but not physical outcomes, at 5 months,” the investigators said (Ann Behav Med. 2018 Feb 9. doi: 10.1093/abm/kax004).
For instance, high-stress patients started the trial with mean scores of about 4.5 on the 42-point cognitive-affective subscale of the Beck Depression Inventory; scores improved to about 2.5 after 5 months of treatment. Low-stress patients, however, started and ended the study with scores of about 1.5.
Cancer-specific stress has been associated with poorer outcomes in previous cancer studies, but its impact on CLL hasn’t been clear until now. It might be a particularly bad problem in CLL, because the disease is incurable and patients go through multiple relapses and treatment cycles.
“There has been a call to screen cancer patients to determine those who may be at risk for poor outcomes, and assessment of cancer-specific stress may have clinical utility as an individual difference predictor of psychological responses,” the team noted.
The mean age in the study was 64.1 years; 71% of the subjects were men. The majority were educated beyond high school, and almost all reported significant, supportive relationships. Patients had a median of three prior therapies, but one patients had been through 16.
Dr. Goyal reported having no financial disclosures. One author disclosed ties to Pharmacyclics and Janssen, marketers of ibrutinib. The work was supported by the National Cancer Institute and Pharmacyclics, among others.
FROM ANNALS OF BEHAVIORAL MEDICINE
CLL Index proves accurate in predicting survival, time to treat
An international prognostic index for patients with chronic lymphocytic leukemia (CLL), known as CLL-IPI, was predictive of time from diagnosis to first treatment (TTFT) and 5-year median overall survival in patients across different risk categories treated with chemoimmunotherapy, according to a systematic review and meta-analysis published in Blood (2018 Jan 18;131[3]:365-8).
But limited data were available for patients treated with targeted therapies that are likely to have a profound effect on overall survival; thereby restricting the use of CLL-IPI in current clinical practice.
Novel therapies such as ibrutinib, idelalisib, and venetoclax have changed the treatment landscape for CLL, Stefano Molica, MD, of Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues wrote. “Because observation remains the standard of care for asymptomatic early-stage patients, the introduction of these agents does not impact the utility of the CLL-IPI for predicting time from diagnosis to first treatment, but it likely has a profound impact on the survival of patients of all risk categories once treatment is indicated.”
The CLL-IPI tool, first published in 2016 to predict clinical outcomes in CLL patients, combines five parameters: age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], immunoglobulin heavy chain–variable mutational status, and serum b2-microglobulin. The prognostic tool was validated across several studies conducted in different countries with diverse practice settings, including academic hospitals, national population-based cohorts, and clinical trials.
The researchers conducted a systematic review and meta-analysis to understand the utility of CLL-IPI tool in predicting OS and TTFT across each risk category of CLL patients.
They included nine studies with 7,843 patients to assess the impact of the CLL-IPI on overall survival. The patient distribution into the CLL-IPI risk categories was low risk (median 45.9%), intermediate risk (median 30%), high risk (median 16.5%), and very high risk (median 3.6%).
The researchers relied on 11 series comprising 7,383 patients to assess 5-year survival probability, which was 92% for low risk, 81% for intermediate risk, 60% for high risk, and 34% for very high risk. They used seven studies comprising 5,206 patients to assess TTFT and found that the probability of remaining treatment free at 5 years was 82% in the low-risk group, 45% in the intermediate-risk group, 30% in the high-risk group, and 16% in the very-high-risk group.
Although a significant step toward harmonizing international prognostication for CLL, additional studies validating the utility of the CLL-IPI for predicting OS in patients treated with targeted therapy are needed, they wrote.
The researchers reported having no financial disclosures.
An international prognostic index for patients with chronic lymphocytic leukemia (CLL), known as CLL-IPI, was predictive of time from diagnosis to first treatment (TTFT) and 5-year median overall survival in patients across different risk categories treated with chemoimmunotherapy, according to a systematic review and meta-analysis published in Blood (2018 Jan 18;131[3]:365-8).
But limited data were available for patients treated with targeted therapies that are likely to have a profound effect on overall survival; thereby restricting the use of CLL-IPI in current clinical practice.
Novel therapies such as ibrutinib, idelalisib, and venetoclax have changed the treatment landscape for CLL, Stefano Molica, MD, of Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues wrote. “Because observation remains the standard of care for asymptomatic early-stage patients, the introduction of these agents does not impact the utility of the CLL-IPI for predicting time from diagnosis to first treatment, but it likely has a profound impact on the survival of patients of all risk categories once treatment is indicated.”
The CLL-IPI tool, first published in 2016 to predict clinical outcomes in CLL patients, combines five parameters: age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], immunoglobulin heavy chain–variable mutational status, and serum b2-microglobulin. The prognostic tool was validated across several studies conducted in different countries with diverse practice settings, including academic hospitals, national population-based cohorts, and clinical trials.
The researchers conducted a systematic review and meta-analysis to understand the utility of CLL-IPI tool in predicting OS and TTFT across each risk category of CLL patients.
They included nine studies with 7,843 patients to assess the impact of the CLL-IPI on overall survival. The patient distribution into the CLL-IPI risk categories was low risk (median 45.9%), intermediate risk (median 30%), high risk (median 16.5%), and very high risk (median 3.6%).
The researchers relied on 11 series comprising 7,383 patients to assess 5-year survival probability, which was 92% for low risk, 81% for intermediate risk, 60% for high risk, and 34% for very high risk. They used seven studies comprising 5,206 patients to assess TTFT and found that the probability of remaining treatment free at 5 years was 82% in the low-risk group, 45% in the intermediate-risk group, 30% in the high-risk group, and 16% in the very-high-risk group.
Although a significant step toward harmonizing international prognostication for CLL, additional studies validating the utility of the CLL-IPI for predicting OS in patients treated with targeted therapy are needed, they wrote.
The researchers reported having no financial disclosures.
An international prognostic index for patients with chronic lymphocytic leukemia (CLL), known as CLL-IPI, was predictive of time from diagnosis to first treatment (TTFT) and 5-year median overall survival in patients across different risk categories treated with chemoimmunotherapy, according to a systematic review and meta-analysis published in Blood (2018 Jan 18;131[3]:365-8).
But limited data were available for patients treated with targeted therapies that are likely to have a profound effect on overall survival; thereby restricting the use of CLL-IPI in current clinical practice.
Novel therapies such as ibrutinib, idelalisib, and venetoclax have changed the treatment landscape for CLL, Stefano Molica, MD, of Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues wrote. “Because observation remains the standard of care for asymptomatic early-stage patients, the introduction of these agents does not impact the utility of the CLL-IPI for predicting time from diagnosis to first treatment, but it likely has a profound impact on the survival of patients of all risk categories once treatment is indicated.”
The CLL-IPI tool, first published in 2016 to predict clinical outcomes in CLL patients, combines five parameters: age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], immunoglobulin heavy chain–variable mutational status, and serum b2-microglobulin. The prognostic tool was validated across several studies conducted in different countries with diverse practice settings, including academic hospitals, national population-based cohorts, and clinical trials.
The researchers conducted a systematic review and meta-analysis to understand the utility of CLL-IPI tool in predicting OS and TTFT across each risk category of CLL patients.
They included nine studies with 7,843 patients to assess the impact of the CLL-IPI on overall survival. The patient distribution into the CLL-IPI risk categories was low risk (median 45.9%), intermediate risk (median 30%), high risk (median 16.5%), and very high risk (median 3.6%).
The researchers relied on 11 series comprising 7,383 patients to assess 5-year survival probability, which was 92% for low risk, 81% for intermediate risk, 60% for high risk, and 34% for very high risk. They used seven studies comprising 5,206 patients to assess TTFT and found that the probability of remaining treatment free at 5 years was 82% in the low-risk group, 45% in the intermediate-risk group, 30% in the high-risk group, and 16% in the very-high-risk group.
Although a significant step toward harmonizing international prognostication for CLL, additional studies validating the utility of the CLL-IPI for predicting OS in patients treated with targeted therapy are needed, they wrote.
The researchers reported having no financial disclosures.
FROM BLOOD
VIDEO: Practice changers out of ASH 2017
ATLANTA – There were a lot of new data presented during the annual meeting of the American Society of Hematology. But what findings could actually change the way you practice?
Robert A. Brodsky, MD, director of the division of hematology at Johns Hopkins University in Baltimore and the moderator for the late-breaking abstract session at ASH, highlighted results from two studies.
Data from the MURANO trial showed robust results for a combination of venetoclax and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). At a median follow-up of 23.8 months, median progression-free survival -had not been reached in patients randomized to venetoclax/rituximab, while patients who received bendamustine plus rituximab had a median PFS of 17 months.
The based on the data presented, Dr. Brodsky said.
Another “enormously exciting and practice-changing” finding is that direct oral anticoagulants can be used safely in patients with cancer, Dr. Brodsky said in an interview.
In a randomized, open-label study, 12 months of daily treatment with edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in cancer patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ATLANTA – There were a lot of new data presented during the annual meeting of the American Society of Hematology. But what findings could actually change the way you practice?
Robert A. Brodsky, MD, director of the division of hematology at Johns Hopkins University in Baltimore and the moderator for the late-breaking abstract session at ASH, highlighted results from two studies.
Data from the MURANO trial showed robust results for a combination of venetoclax and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). At a median follow-up of 23.8 months, median progression-free survival -had not been reached in patients randomized to venetoclax/rituximab, while patients who received bendamustine plus rituximab had a median PFS of 17 months.
The based on the data presented, Dr. Brodsky said.
Another “enormously exciting and practice-changing” finding is that direct oral anticoagulants can be used safely in patients with cancer, Dr. Brodsky said in an interview.
In a randomized, open-label study, 12 months of daily treatment with edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in cancer patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ATLANTA – There were a lot of new data presented during the annual meeting of the American Society of Hematology. But what findings could actually change the way you practice?
Robert A. Brodsky, MD, director of the division of hematology at Johns Hopkins University in Baltimore and the moderator for the late-breaking abstract session at ASH, highlighted results from two studies.
Data from the MURANO trial showed robust results for a combination of venetoclax and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). At a median follow-up of 23.8 months, median progression-free survival -had not been reached in patients randomized to venetoclax/rituximab, while patients who received bendamustine plus rituximab had a median PFS of 17 months.
The based on the data presented, Dr. Brodsky said.
Another “enormously exciting and practice-changing” finding is that direct oral anticoagulants can be used safely in patients with cancer, Dr. Brodsky said in an interview.
In a randomized, open-label study, 12 months of daily treatment with edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in cancer patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
REPORTING FROM ASH 2017
CLL drug in limited supply outside U.S.
Ofatumumab (Arzerra), a monoclonal antibody treatment for chronic lymphocytic leukemia, will soon be available outside the United States through compassionate use programs only. The drug will continue to be widely available in the United States.
Novartis announced in January that it would begin limiting the availability of the drug outside of the United States and would work with regulatory authorities to set up compassionate use programs for patients who are currently being treated with the drug. Patients who use these programs will receive the drug for free.
The decision was driven by the surge in CLL drugs that have become available over the last 5 years, according to Novartis.
The decision to pull the drug from international markets will not affect its use in ongoing clinical trials, particularly two phase 3 studies in relapsing multiple sclerosis and indolent non-Hodgkin lymphoma.
Ofatumumab (Arzerra), a monoclonal antibody treatment for chronic lymphocytic leukemia, will soon be available outside the United States through compassionate use programs only. The drug will continue to be widely available in the United States.
Novartis announced in January that it would begin limiting the availability of the drug outside of the United States and would work with regulatory authorities to set up compassionate use programs for patients who are currently being treated with the drug. Patients who use these programs will receive the drug for free.
The decision was driven by the surge in CLL drugs that have become available over the last 5 years, according to Novartis.
The decision to pull the drug from international markets will not affect its use in ongoing clinical trials, particularly two phase 3 studies in relapsing multiple sclerosis and indolent non-Hodgkin lymphoma.
Ofatumumab (Arzerra), a monoclonal antibody treatment for chronic lymphocytic leukemia, will soon be available outside the United States through compassionate use programs only. The drug will continue to be widely available in the United States.
Novartis announced in January that it would begin limiting the availability of the drug outside of the United States and would work with regulatory authorities to set up compassionate use programs for patients who are currently being treated with the drug. Patients who use these programs will receive the drug for free.
The decision was driven by the surge in CLL drugs that have become available over the last 5 years, according to Novartis.
The decision to pull the drug from international markets will not affect its use in ongoing clinical trials, particularly two phase 3 studies in relapsing multiple sclerosis and indolent non-Hodgkin lymphoma.
Venetoclax/rituximab boosts PFS in relapsed/refractory CLL
ATLANTA – In patients with relapsed/refractory chronic lymphocytic leukemia (CLL), a combination of venetoclax (Venclexta) and rituximab was superior to bendamustine (Treanda) and rituximab for prolonging progression-free survival (PFS), with effects consistent across subgroups, regardless of mutational status, and a clinically meaningful improvement in overall survival.
An interim analysis from the phase 3 MURANO trial showed that after a median follow-up of 23.8 months, the median PFS for patients randomized to venetoclax/rituximab had not been reached, compared with 17 months for patients assigned to bendamustine/rituximab, reported John F. Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre at the University of Melbourne.
Relapsed/refractory CLL often has a suboptimal response to conventional chemotherapy because of adverse biological features that can accumulate in cells, he said.
The combination of bendamustine and rituximab has been associated with about 60% overall responses rates, a median PFS of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, he noted.
The rationale for pairing venetoclax with rituximab in this population comes from evidence showing efficacy of the monoclonal antibody, an oral B-cell lymphoma–2 (BCL-2) inhibitor, as monotherapy in patients with relapsed/refractory CLL, including those with poor prognostic features such as the 17p deletion (del17p).
Dr. Seymour and his colleagues recently published results from a phase 1b trial of venetoclax/rituximab in patients with relapsed/refractory CLL. The combination was associated with a 51% complete response rate, and a 28% rate of negative marrow minimal residual disease (MRD) (Lancet Oncol. 2017 Feb;18[2]:230-40)
In the MURANO study (NCT02005471), the investigators evaluated whether time-limited therapy with venetoclax/rituximab could improve PFS over bendamustine/rituximab.
Patients 18 and older with CLL who had been treated with one to three prior lines of therapy, including at least one chemotherapy-containing regimen, were enrolled. Prior treatment with bendamustine was allowed only if patients had had a duration of response of at least 24 months.
After stratification by del17p status, responsiveness to prior therapy, and geographic region, 389 patients were randomly assigned to receive rituximab 375 mg/m2 on day 1 of cycle 1 and 500 mg/m2 on day 1 of cycles 2 through 6, plus either bendamustine 70 mg/m2 on days 1 and 2 of each of six cycles, or venetoclax 400 mg orally once daily until disease progression, cessation for toxicity, or up to a maximum of 2 years starting from day 1 of cycle 1.
As noted,
The respective 1- and 2-year PFS rates with venetoclax were 91.2% and 82.8%, compared with 74.1% and 37.4% with bendamustine.
The venetoclax/rituximab combination was also significantly superior across all subgroups, regardless of the number of prior therapies, refractory vs. relapsed after most recent prior therapy, del17p status, TP53 mutational status, or baseline immunoglobulin heavy chain variable (IGHV) mutated or unmutated status
Response rates assessed by both investigators and independent reviewers were also better with venetoclax. The investigator-assessed overall response rate (ORR) was 93.3%, compared with 67.7% for bendamustine/rituximab, including 26.8% complete responses (CR), compared with 8.2%. Independent reviewers decreed an ORR of 92.3% for venentoclax, vs. 72.3% for bendamustine, including respective CR rates of 8.2% and 3.6%.
The investigators also found that the percentage of MRD negativity was higher with venetoclax/rituximab, with 62% of patients in this group being MRD negative at 9 months. This rate remained fairly constant at 12-, 15- and 18-month follow-ups (60%, 57%, and 60%, respectively).
In contrast, 13% of patients treated with bendamustine were MRD negative at 9 months, and the rates gradually declined over time to 10%, 9%, and 5%.
Investigators also saw a clinically meaningful improvement in overall survival with the venetoclax/rituximab duo, although survival data are still not mature in this ongoing trial. The median OS had not been reached in either group at the time of data cutoff.
Respective 1- and 2-year OS rates with venetoclax were 95.9% and 91.9%, and with bendamustine were 91.1% and 86.6%.
At the time of this interim analysis, the hazard ratio favoring venetoclax/rituximab was 0.48 (P = .0186).
Drug discontinuation was more frequent with venetoclax/rituximab (25% vs, 17%), with disease progression and adverse events without progression being the most frequent reasons for stopping in each arm.
Serious adverse events occurred in 46% of patients on venetoclax/rituximab and 43% on bendamustine/rituximab. A higher percentage of patients on venetoclax/rituximab had grade 3 or 4 adverse events (82% vs, 70%). Ten patients (5%) in the venetoclax/rituximab arm died, and 11 patients (6%) on bendamustine/rituximab died.
Events with a greater than 2% difference included more frequent neutropenia, tumor lysis syndrome, hyperglycemia and hypogammaglobulinema with venetoclax/rituximab, and more frequent anemia, thrombocytopenia, febrile neutropenia, pneumonia, infusion-related reactions, and hypotension with bendamustine/rituximab.
In the question-and-response portion following Dr. Seymour’s presentation, an audience member commented that the continuation of venetoclax/rituximab beyond the initial treatment cycles amounted to a maintenance strategy, and that patients in the experimental arm were in treatment longer, which likely influenced the results.
“You’re absolutely correct that the treatment duration differed, although, of course, the capacity to deliver more than six cycles of bendamustine/rituximab would have been problematic,” Dr. Seymour replied.
“There are some data that antibody treatment may prolong progression-free survival. However, when this study was designed in 2013 that data was certainly not available, and I believe currently even maintenance antibodies are not an accepted standard of treatment,” he added.
The MURANO trial was funded by AbbVie and Genentech. Dr. Seymour disclosed honoraria, speakers bureau, research funding, and advisory activities with AbbVie and other companies.
SOURCE: Seymour J et al. ASH 2017 LBA-2.
ATLANTA – In patients with relapsed/refractory chronic lymphocytic leukemia (CLL), a combination of venetoclax (Venclexta) and rituximab was superior to bendamustine (Treanda) and rituximab for prolonging progression-free survival (PFS), with effects consistent across subgroups, regardless of mutational status, and a clinically meaningful improvement in overall survival.
An interim analysis from the phase 3 MURANO trial showed that after a median follow-up of 23.8 months, the median PFS for patients randomized to venetoclax/rituximab had not been reached, compared with 17 months for patients assigned to bendamustine/rituximab, reported John F. Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre at the University of Melbourne.
Relapsed/refractory CLL often has a suboptimal response to conventional chemotherapy because of adverse biological features that can accumulate in cells, he said.
The combination of bendamustine and rituximab has been associated with about 60% overall responses rates, a median PFS of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, he noted.
The rationale for pairing venetoclax with rituximab in this population comes from evidence showing efficacy of the monoclonal antibody, an oral B-cell lymphoma–2 (BCL-2) inhibitor, as monotherapy in patients with relapsed/refractory CLL, including those with poor prognostic features such as the 17p deletion (del17p).
Dr. Seymour and his colleagues recently published results from a phase 1b trial of venetoclax/rituximab in patients with relapsed/refractory CLL. The combination was associated with a 51% complete response rate, and a 28% rate of negative marrow minimal residual disease (MRD) (Lancet Oncol. 2017 Feb;18[2]:230-40)
In the MURANO study (NCT02005471), the investigators evaluated whether time-limited therapy with venetoclax/rituximab could improve PFS over bendamustine/rituximab.
Patients 18 and older with CLL who had been treated with one to three prior lines of therapy, including at least one chemotherapy-containing regimen, were enrolled. Prior treatment with bendamustine was allowed only if patients had had a duration of response of at least 24 months.
After stratification by del17p status, responsiveness to prior therapy, and geographic region, 389 patients were randomly assigned to receive rituximab 375 mg/m2 on day 1 of cycle 1 and 500 mg/m2 on day 1 of cycles 2 through 6, plus either bendamustine 70 mg/m2 on days 1 and 2 of each of six cycles, or venetoclax 400 mg orally once daily until disease progression, cessation for toxicity, or up to a maximum of 2 years starting from day 1 of cycle 1.
As noted,
The respective 1- and 2-year PFS rates with venetoclax were 91.2% and 82.8%, compared with 74.1% and 37.4% with bendamustine.
The venetoclax/rituximab combination was also significantly superior across all subgroups, regardless of the number of prior therapies, refractory vs. relapsed after most recent prior therapy, del17p status, TP53 mutational status, or baseline immunoglobulin heavy chain variable (IGHV) mutated or unmutated status
Response rates assessed by both investigators and independent reviewers were also better with venetoclax. The investigator-assessed overall response rate (ORR) was 93.3%, compared with 67.7% for bendamustine/rituximab, including 26.8% complete responses (CR), compared with 8.2%. Independent reviewers decreed an ORR of 92.3% for venentoclax, vs. 72.3% for bendamustine, including respective CR rates of 8.2% and 3.6%.
The investigators also found that the percentage of MRD negativity was higher with venetoclax/rituximab, with 62% of patients in this group being MRD negative at 9 months. This rate remained fairly constant at 12-, 15- and 18-month follow-ups (60%, 57%, and 60%, respectively).
In contrast, 13% of patients treated with bendamustine were MRD negative at 9 months, and the rates gradually declined over time to 10%, 9%, and 5%.
Investigators also saw a clinically meaningful improvement in overall survival with the venetoclax/rituximab duo, although survival data are still not mature in this ongoing trial. The median OS had not been reached in either group at the time of data cutoff.
Respective 1- and 2-year OS rates with venetoclax were 95.9% and 91.9%, and with bendamustine were 91.1% and 86.6%.
At the time of this interim analysis, the hazard ratio favoring venetoclax/rituximab was 0.48 (P = .0186).
Drug discontinuation was more frequent with venetoclax/rituximab (25% vs, 17%), with disease progression and adverse events without progression being the most frequent reasons for stopping in each arm.
Serious adverse events occurred in 46% of patients on venetoclax/rituximab and 43% on bendamustine/rituximab. A higher percentage of patients on venetoclax/rituximab had grade 3 or 4 adverse events (82% vs, 70%). Ten patients (5%) in the venetoclax/rituximab arm died, and 11 patients (6%) on bendamustine/rituximab died.
Events with a greater than 2% difference included more frequent neutropenia, tumor lysis syndrome, hyperglycemia and hypogammaglobulinema with venetoclax/rituximab, and more frequent anemia, thrombocytopenia, febrile neutropenia, pneumonia, infusion-related reactions, and hypotension with bendamustine/rituximab.
In the question-and-response portion following Dr. Seymour’s presentation, an audience member commented that the continuation of venetoclax/rituximab beyond the initial treatment cycles amounted to a maintenance strategy, and that patients in the experimental arm were in treatment longer, which likely influenced the results.
“You’re absolutely correct that the treatment duration differed, although, of course, the capacity to deliver more than six cycles of bendamustine/rituximab would have been problematic,” Dr. Seymour replied.
“There are some data that antibody treatment may prolong progression-free survival. However, when this study was designed in 2013 that data was certainly not available, and I believe currently even maintenance antibodies are not an accepted standard of treatment,” he added.
The MURANO trial was funded by AbbVie and Genentech. Dr. Seymour disclosed honoraria, speakers bureau, research funding, and advisory activities with AbbVie and other companies.
SOURCE: Seymour J et al. ASH 2017 LBA-2.
ATLANTA – In patients with relapsed/refractory chronic lymphocytic leukemia (CLL), a combination of venetoclax (Venclexta) and rituximab was superior to bendamustine (Treanda) and rituximab for prolonging progression-free survival (PFS), with effects consistent across subgroups, regardless of mutational status, and a clinically meaningful improvement in overall survival.
An interim analysis from the phase 3 MURANO trial showed that after a median follow-up of 23.8 months, the median PFS for patients randomized to venetoclax/rituximab had not been reached, compared with 17 months for patients assigned to bendamustine/rituximab, reported John F. Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre at the University of Melbourne.
Relapsed/refractory CLL often has a suboptimal response to conventional chemotherapy because of adverse biological features that can accumulate in cells, he said.
The combination of bendamustine and rituximab has been associated with about 60% overall responses rates, a median PFS of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, he noted.
The rationale for pairing venetoclax with rituximab in this population comes from evidence showing efficacy of the monoclonal antibody, an oral B-cell lymphoma–2 (BCL-2) inhibitor, as monotherapy in patients with relapsed/refractory CLL, including those with poor prognostic features such as the 17p deletion (del17p).
Dr. Seymour and his colleagues recently published results from a phase 1b trial of venetoclax/rituximab in patients with relapsed/refractory CLL. The combination was associated with a 51% complete response rate, and a 28% rate of negative marrow minimal residual disease (MRD) (Lancet Oncol. 2017 Feb;18[2]:230-40)
In the MURANO study (NCT02005471), the investigators evaluated whether time-limited therapy with venetoclax/rituximab could improve PFS over bendamustine/rituximab.
Patients 18 and older with CLL who had been treated with one to three prior lines of therapy, including at least one chemotherapy-containing regimen, were enrolled. Prior treatment with bendamustine was allowed only if patients had had a duration of response of at least 24 months.
After stratification by del17p status, responsiveness to prior therapy, and geographic region, 389 patients were randomly assigned to receive rituximab 375 mg/m2 on day 1 of cycle 1 and 500 mg/m2 on day 1 of cycles 2 through 6, plus either bendamustine 70 mg/m2 on days 1 and 2 of each of six cycles, or venetoclax 400 mg orally once daily until disease progression, cessation for toxicity, or up to a maximum of 2 years starting from day 1 of cycle 1.
As noted,
The respective 1- and 2-year PFS rates with venetoclax were 91.2% and 82.8%, compared with 74.1% and 37.4% with bendamustine.
The venetoclax/rituximab combination was also significantly superior across all subgroups, regardless of the number of prior therapies, refractory vs. relapsed after most recent prior therapy, del17p status, TP53 mutational status, or baseline immunoglobulin heavy chain variable (IGHV) mutated or unmutated status
Response rates assessed by both investigators and independent reviewers were also better with venetoclax. The investigator-assessed overall response rate (ORR) was 93.3%, compared with 67.7% for bendamustine/rituximab, including 26.8% complete responses (CR), compared with 8.2%. Independent reviewers decreed an ORR of 92.3% for venentoclax, vs. 72.3% for bendamustine, including respective CR rates of 8.2% and 3.6%.
The investigators also found that the percentage of MRD negativity was higher with venetoclax/rituximab, with 62% of patients in this group being MRD negative at 9 months. This rate remained fairly constant at 12-, 15- and 18-month follow-ups (60%, 57%, and 60%, respectively).
In contrast, 13% of patients treated with bendamustine were MRD negative at 9 months, and the rates gradually declined over time to 10%, 9%, and 5%.
Investigators also saw a clinically meaningful improvement in overall survival with the venetoclax/rituximab duo, although survival data are still not mature in this ongoing trial. The median OS had not been reached in either group at the time of data cutoff.
Respective 1- and 2-year OS rates with venetoclax were 95.9% and 91.9%, and with bendamustine were 91.1% and 86.6%.
At the time of this interim analysis, the hazard ratio favoring venetoclax/rituximab was 0.48 (P = .0186).
Drug discontinuation was more frequent with venetoclax/rituximab (25% vs, 17%), with disease progression and adverse events without progression being the most frequent reasons for stopping in each arm.
Serious adverse events occurred in 46% of patients on venetoclax/rituximab and 43% on bendamustine/rituximab. A higher percentage of patients on venetoclax/rituximab had grade 3 or 4 adverse events (82% vs, 70%). Ten patients (5%) in the venetoclax/rituximab arm died, and 11 patients (6%) on bendamustine/rituximab died.
Events with a greater than 2% difference included more frequent neutropenia, tumor lysis syndrome, hyperglycemia and hypogammaglobulinema with venetoclax/rituximab, and more frequent anemia, thrombocytopenia, febrile neutropenia, pneumonia, infusion-related reactions, and hypotension with bendamustine/rituximab.
In the question-and-response portion following Dr. Seymour’s presentation, an audience member commented that the continuation of venetoclax/rituximab beyond the initial treatment cycles amounted to a maintenance strategy, and that patients in the experimental arm were in treatment longer, which likely influenced the results.
“You’re absolutely correct that the treatment duration differed, although, of course, the capacity to deliver more than six cycles of bendamustine/rituximab would have been problematic,” Dr. Seymour replied.
“There are some data that antibody treatment may prolong progression-free survival. However, when this study was designed in 2013 that data was certainly not available, and I believe currently even maintenance antibodies are not an accepted standard of treatment,” he added.
The MURANO trial was funded by AbbVie and Genentech. Dr. Seymour disclosed honoraria, speakers bureau, research funding, and advisory activities with AbbVie and other companies.
SOURCE: Seymour J et al. ASH 2017 LBA-2.
REPORTING FROM ASH 2017
Key clinical point: Compared with bendamustine/rituximab, venetoclax/rituximab was associated with significantly superior progression-free survival of relapsed/refractory chronic lymphocytic leukemia.
Major finding: The hazard ratio for PFS with venetoclax/rituximab was 0.17 (P less than .001).
Data source: A randomized phase 3, open-label trial in 389 patients with relapsed/refractory CLL.
Disclosures: The MURANO trial was funded by AbbVie and Genetech. Dr. Seymour disclosed honoraria, speakers bureau, research funding, and advisory activities with AbbVie and other companies.
Source: Seymour J et al. ASH 2017 LBA-2.
VIDEO: Venetoclax/rituximab prolongs PFS in relapsed/refractory CLL
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
REPORTING FROM ASH 2017
CLL drug combinations induce MRD negativity
Atlanta – The potential of two- and three-drug combinations to induce deep, minimal residual disease (MRD)–negative responses in patients with chronic lymphocytic leukemia (CLL) was demonstrated in multiple studies presented at the annual meeting of the American Society of Hematology.
Previous studies have suggested that, in contrast to single-agent kinase inhibitor treatment, combinations of treatments, namely kinase or B-cell lyphoma 2 inhibitors combined with anti-CD20 antibodies, can induce MRD negativity at a high rate. For example, in a report on the CLL14 trial, 11 of 12 previously untreated patients were MRD negative after treatment with the BCL-2 inhibitor venetoclax and anti-CD20 antibody obinutuzumab (Blood. 2017;129:2702-5. doi:10.1182/blood-2017-01-761973).
This new batch of studies presented at ASH 2017 provided additional evidence for the venetoclax and obinutuzumab combination, as well as other combinations that appear to provide favorable rates of MRD-negative CLL, including obinutuzumab and venetoclax plus ibrutinib and, notably, a combination that included venetoclax and ibrutinib but no anti-CD20 antibody.
A phase II trial presented by Nitin Jain, MD, of MD Anderson Cancer Center, Houston, looked at the combination of venetoclax and ibrutinib for patients with previously untreated high-risk CLL or relapsed/refractory CLL. The regimen under evaluation starts with daily ibrutinib monotherapy for 3 months before venetoclax is added.
For the first line cohort of 36 patients, the bone marrow MRD-negativity proportion was 0% after 3 months of ibrutinib and 21% after 3 months of ibrutinib plus venetoclax, then 45%, 80%, and 100%, respectively, after 6, 9, and 12 months of combination therapy, Dr. Jain reported. In the relapsed/refractory cohort, MRD negativity was 8% after 3 months of combination therapy and 40% after 12 months. “Responses continue to improve with time, with many patients achieving bone marrow MRD-negative remission,” Dr. Jain said.
The study showed “very impressive MRD rates,” commented Ian W. Flinn, MD, of Sarah Cannon Research Institute, Nashville, Tenn. “I think it’s still up for further discussion and research to find which is the best combination.”
Dr. Flinn presented results from a phase Ib GP28331 study of venetoclax and obinutuzumab in patients with previously untreated CLL in which MRD was assessed in peripheral blood and bone marrow.
All 32 patients achieved peripheral blood negativity at some point on study, Dr. Flinn said, and 75% achieved bone marrow negativity. The complete response rate was 72% (23/32), but notably, high rates of undetectable bone marrow MRD were seen irrespective of response status, Dr. Flinn said.
All patients had at least one adverse event, with grade 3-4 neutropenia, febrile neutropenia, and thrombocytopenia reported most commonly.
Preliminary progression-free survival data (PFS) suggested “durable clinical outcomes” for the combination, with an estimated 18-month PFS of 90.5%, he said.
A third study assessed the combination of obinutuzumab, ibrutinib, and venetoclax, finding that the combination induced MRD negativity in 14 of 24 (58%) treatment-naive CLL patients, according to Kerry A. Rogers, MD, of Ohio State University, Columbus.
The combination had a 96% response rate and is “extremely effective at eliminating detectable CLL,” Dr. Rogers noted.
Most adverse events were hematologic, and high-grade adverse events were rare, she said.
Results for the study’s primary endpoint, rate of MRD-negative complete remission, are expected by May 2018, Dr. Rogers said, adding that further follow-up will be needed to determine PFS for the combination.
Session attendees asked presenters whether they felt there was scientific justification for inclusion of the anti-CD20 antibody rituximab in future trials designed in part to assess MRD negativity.
“I think that obinutuzumab has greater efficacy in patients with CLL, compared to rituximab, and so our hypothesis is that it is a superior antibody to combine with venetoclax,” Dr. Flinn said.
AbbVie provided funding for the study on venetoclax and ibrutinib. Dr. Jain reported disclosures from venetoclax makers AbbVie and Genentech, ibrutinib makers Janssen and Pharmacyclics, and others.
Genentech and AbbVie provided support for the study on venetoclax and obinutuzumab. Dr. Flinn reported disclosures related to both companies and others.
Dr. Rogers reported no conflicts related to the study on obinutuzumab, ibrutinib, and venetoclax. One of her associates reported disclosures related to ibrutinib makers Novartis and Pharmacylics, among others.
SOURCE: Jain N et al. ASH 2017 Abstract 429; Flinn I et al. ASH 2017 Abstract 430; Rogers K et al. ASH 2017 Abstract 431.
Atlanta – The potential of two- and three-drug combinations to induce deep, minimal residual disease (MRD)–negative responses in patients with chronic lymphocytic leukemia (CLL) was demonstrated in multiple studies presented at the annual meeting of the American Society of Hematology.
Previous studies have suggested that, in contrast to single-agent kinase inhibitor treatment, combinations of treatments, namely kinase or B-cell lyphoma 2 inhibitors combined with anti-CD20 antibodies, can induce MRD negativity at a high rate. For example, in a report on the CLL14 trial, 11 of 12 previously untreated patients were MRD negative after treatment with the BCL-2 inhibitor venetoclax and anti-CD20 antibody obinutuzumab (Blood. 2017;129:2702-5. doi:10.1182/blood-2017-01-761973).
This new batch of studies presented at ASH 2017 provided additional evidence for the venetoclax and obinutuzumab combination, as well as other combinations that appear to provide favorable rates of MRD-negative CLL, including obinutuzumab and venetoclax plus ibrutinib and, notably, a combination that included venetoclax and ibrutinib but no anti-CD20 antibody.
A phase II trial presented by Nitin Jain, MD, of MD Anderson Cancer Center, Houston, looked at the combination of venetoclax and ibrutinib for patients with previously untreated high-risk CLL or relapsed/refractory CLL. The regimen under evaluation starts with daily ibrutinib monotherapy for 3 months before venetoclax is added.
For the first line cohort of 36 patients, the bone marrow MRD-negativity proportion was 0% after 3 months of ibrutinib and 21% after 3 months of ibrutinib plus venetoclax, then 45%, 80%, and 100%, respectively, after 6, 9, and 12 months of combination therapy, Dr. Jain reported. In the relapsed/refractory cohort, MRD negativity was 8% after 3 months of combination therapy and 40% after 12 months. “Responses continue to improve with time, with many patients achieving bone marrow MRD-negative remission,” Dr. Jain said.
The study showed “very impressive MRD rates,” commented Ian W. Flinn, MD, of Sarah Cannon Research Institute, Nashville, Tenn. “I think it’s still up for further discussion and research to find which is the best combination.”
Dr. Flinn presented results from a phase Ib GP28331 study of venetoclax and obinutuzumab in patients with previously untreated CLL in which MRD was assessed in peripheral blood and bone marrow.
All 32 patients achieved peripheral blood negativity at some point on study, Dr. Flinn said, and 75% achieved bone marrow negativity. The complete response rate was 72% (23/32), but notably, high rates of undetectable bone marrow MRD were seen irrespective of response status, Dr. Flinn said.
All patients had at least one adverse event, with grade 3-4 neutropenia, febrile neutropenia, and thrombocytopenia reported most commonly.
Preliminary progression-free survival data (PFS) suggested “durable clinical outcomes” for the combination, with an estimated 18-month PFS of 90.5%, he said.
A third study assessed the combination of obinutuzumab, ibrutinib, and venetoclax, finding that the combination induced MRD negativity in 14 of 24 (58%) treatment-naive CLL patients, according to Kerry A. Rogers, MD, of Ohio State University, Columbus.
The combination had a 96% response rate and is “extremely effective at eliminating detectable CLL,” Dr. Rogers noted.
Most adverse events were hematologic, and high-grade adverse events were rare, she said.
Results for the study’s primary endpoint, rate of MRD-negative complete remission, are expected by May 2018, Dr. Rogers said, adding that further follow-up will be needed to determine PFS for the combination.
Session attendees asked presenters whether they felt there was scientific justification for inclusion of the anti-CD20 antibody rituximab in future trials designed in part to assess MRD negativity.
“I think that obinutuzumab has greater efficacy in patients with CLL, compared to rituximab, and so our hypothesis is that it is a superior antibody to combine with venetoclax,” Dr. Flinn said.
AbbVie provided funding for the study on venetoclax and ibrutinib. Dr. Jain reported disclosures from venetoclax makers AbbVie and Genentech, ibrutinib makers Janssen and Pharmacyclics, and others.
Genentech and AbbVie provided support for the study on venetoclax and obinutuzumab. Dr. Flinn reported disclosures related to both companies and others.
Dr. Rogers reported no conflicts related to the study on obinutuzumab, ibrutinib, and venetoclax. One of her associates reported disclosures related to ibrutinib makers Novartis and Pharmacylics, among others.
SOURCE: Jain N et al. ASH 2017 Abstract 429; Flinn I et al. ASH 2017 Abstract 430; Rogers K et al. ASH 2017 Abstract 431.
Atlanta – The potential of two- and three-drug combinations to induce deep, minimal residual disease (MRD)–negative responses in patients with chronic lymphocytic leukemia (CLL) was demonstrated in multiple studies presented at the annual meeting of the American Society of Hematology.
Previous studies have suggested that, in contrast to single-agent kinase inhibitor treatment, combinations of treatments, namely kinase or B-cell lyphoma 2 inhibitors combined with anti-CD20 antibodies, can induce MRD negativity at a high rate. For example, in a report on the CLL14 trial, 11 of 12 previously untreated patients were MRD negative after treatment with the BCL-2 inhibitor venetoclax and anti-CD20 antibody obinutuzumab (Blood. 2017;129:2702-5. doi:10.1182/blood-2017-01-761973).
This new batch of studies presented at ASH 2017 provided additional evidence for the venetoclax and obinutuzumab combination, as well as other combinations that appear to provide favorable rates of MRD-negative CLL, including obinutuzumab and venetoclax plus ibrutinib and, notably, a combination that included venetoclax and ibrutinib but no anti-CD20 antibody.
A phase II trial presented by Nitin Jain, MD, of MD Anderson Cancer Center, Houston, looked at the combination of venetoclax and ibrutinib for patients with previously untreated high-risk CLL or relapsed/refractory CLL. The regimen under evaluation starts with daily ibrutinib monotherapy for 3 months before venetoclax is added.
For the first line cohort of 36 patients, the bone marrow MRD-negativity proportion was 0% after 3 months of ibrutinib and 21% after 3 months of ibrutinib plus venetoclax, then 45%, 80%, and 100%, respectively, after 6, 9, and 12 months of combination therapy, Dr. Jain reported. In the relapsed/refractory cohort, MRD negativity was 8% after 3 months of combination therapy and 40% after 12 months. “Responses continue to improve with time, with many patients achieving bone marrow MRD-negative remission,” Dr. Jain said.
The study showed “very impressive MRD rates,” commented Ian W. Flinn, MD, of Sarah Cannon Research Institute, Nashville, Tenn. “I think it’s still up for further discussion and research to find which is the best combination.”
Dr. Flinn presented results from a phase Ib GP28331 study of venetoclax and obinutuzumab in patients with previously untreated CLL in which MRD was assessed in peripheral blood and bone marrow.
All 32 patients achieved peripheral blood negativity at some point on study, Dr. Flinn said, and 75% achieved bone marrow negativity. The complete response rate was 72% (23/32), but notably, high rates of undetectable bone marrow MRD were seen irrespective of response status, Dr. Flinn said.
All patients had at least one adverse event, with grade 3-4 neutropenia, febrile neutropenia, and thrombocytopenia reported most commonly.
Preliminary progression-free survival data (PFS) suggested “durable clinical outcomes” for the combination, with an estimated 18-month PFS of 90.5%, he said.
A third study assessed the combination of obinutuzumab, ibrutinib, and venetoclax, finding that the combination induced MRD negativity in 14 of 24 (58%) treatment-naive CLL patients, according to Kerry A. Rogers, MD, of Ohio State University, Columbus.
The combination had a 96% response rate and is “extremely effective at eliminating detectable CLL,” Dr. Rogers noted.
Most adverse events were hematologic, and high-grade adverse events were rare, she said.
Results for the study’s primary endpoint, rate of MRD-negative complete remission, are expected by May 2018, Dr. Rogers said, adding that further follow-up will be needed to determine PFS for the combination.
Session attendees asked presenters whether they felt there was scientific justification for inclusion of the anti-CD20 antibody rituximab in future trials designed in part to assess MRD negativity.
“I think that obinutuzumab has greater efficacy in patients with CLL, compared to rituximab, and so our hypothesis is that it is a superior antibody to combine with venetoclax,” Dr. Flinn said.
AbbVie provided funding for the study on venetoclax and ibrutinib. Dr. Jain reported disclosures from venetoclax makers AbbVie and Genentech, ibrutinib makers Janssen and Pharmacyclics, and others.
Genentech and AbbVie provided support for the study on venetoclax and obinutuzumab. Dr. Flinn reported disclosures related to both companies and others.
Dr. Rogers reported no conflicts related to the study on obinutuzumab, ibrutinib, and venetoclax. One of her associates reported disclosures related to ibrutinib makers Novartis and Pharmacylics, among others.
SOURCE: Jain N et al. ASH 2017 Abstract 429; Flinn I et al. ASH 2017 Abstract 430; Rogers K et al. ASH 2017 Abstract 431.
REPORTING FROM ASH 2017
CLARITY: Ibrutinib/venetoclax combo results look promising for relapsed/refractory CLL
ATLANTA – Combination therapy with ibrutinib and venetoclax is well tolerated and shows promise for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), according to initial results from the CLARITY feasibility trial.
Of 38 patients who received at least 6 months of treatment with combination ibrutinib (Imbruvica)/venetoclax (Venclexta) and reached month 8 – and therefore had computed tomography, clinical data, and peripheral blood and marrow assessments available – 15 (37%) achieved peripheral blood minimal residual disease (MRD) negativity, and 12 (32%) achieved bone marrow MRD negativity, Peter Hillmen, MBChB, PhD, reported during a press briefing at the annual meeting of the American Society of Hematology.
The rates of MRD negativity in the blood and marrow, and of normal trephine biopsy, were similar in subsets of patients who relapsed within 36 months of prior treatment with fludarabine/cyclophosphamide/rituximab (FCR) or bendamustine/rituximab (BR), and with prior idelalisib exposure, he noted.
“In terms of [International Workshop on Chronic Lymphocytic Leukemia] response criteria, which is a secondary endpoint, 47% of patients achieved a [complete remission or complete remission with incomplete hematologic recovery] and every patient has had an overall response, which for this group of patients is impressive,” he said.
Again, the findings were similar in those who were refractory to prior FCR/BR or to previous idelalisib, he noted.
Both ibrutinib and venetoclax are approved as single agents for the treatment of CLL. Ibrutinib is a Bruton’s tyrosine kinase inhibitor that has had a major effect on patient outcomes, showing overall survival advantages in numerous trials, Dr. Hillmen said.
“However, ibrutinib does not eradicate disease, and patients remain on treatment indefinitely or until progression,” he said.
Venetoclax is a highly selective B cell lymphoma–2 inhibitor approved for refractory CLL in patients with 17p deletion. It has a rapid effect, which can lead to tumor lysis syndrome, but also leads to eradication of MRD in some patients, which can lead to prolonged survival, he said.
The CLARITY trial was designed to investigate the safety and efficacy of the two in combination in relapsed/refractory CLL patients.
The primary endpoint of the study is MRD eradication in the marrow after 12 months of treatment. The current analysis looks at a key secondary endpoint of the study – MRD eradication in the marrow after 6 months of treatment.
The study enrolled 54 patients, including 37 men and 17 women with a median age of 64 years; 20% have 17p deletion, and the population was heavily pretreated, with 81% having prior FCR or BR (44% with relapse within 3 years of treatment), and 20% with previous idelalisib exposure. Patients were excluded if they had prior exposure to ibrutinib or venetoclax.
Treatment involves ibrutinib monotherapy at a dose of 420 mg/day for 2 months to debulk the disease, after which venetoclax is added at a dose escalating from 20 mg to 400 mg/day over 2 months to reduce the risk of tumor lysis syndrome.
Bone marrow biopsies are performed at 6, 12, and 24 months. Treatment is discontinued at 12 months in those who achieve MRD negativity at 6 months, and is discontinued at 24 months in those who achieve MRD negativity at 12 months.
The combination treatment was well tolerated in the first 38 patients. Bruising (mainly grade 1) occurred in 33 patients, and neutropenia (including 16 grade 3 cases and 6 grade 4 cases) occurred in 25, and some GI toxicity occurred, but was largely grade 1 or 2, Dr. Hillmen said.
“There really was otherwise very acceptable toxicity,” he added, noting that a single case of tumor lysis syndrome occurred, but was managed successfully by delaying venetoclax.
“That patient re-escalated back onto treatment and is doing well,” he said.
No patients stopped treatment, and only seven had treatment interruption, and then only for a few days, he noted.
The findings are encouraging, and suggest a potent synergy between ibrutinib and venetoclax, said Dr. Hillmen.
“We’re seeing, even at this very early stage, over 30% of patients achieving MRD negative remission, which was our target at the 12-month bone marrow stage with this combination,” he said.
In light of these results, the ongoing phase 3 FLAIR trial, which is actively recruiting, has been modified to include combination ibrutinib and venetoclax in front-line CLL, he said.
Dr. Hillmen reported financial relationships with AbbVie and several other pharmaceutical companies. The CLARITY trial is supported by AbbVie, Bloodwise, Experimental Cancer Medicine Centre, Janssen-Cilag, the National Institute for Health Research Clinical Research Network: Cancer, and the University of Birmingham (England).
[email protected]
SOURCE: Hillmen P et al., ASH abstract 428.
ATLANTA – Combination therapy with ibrutinib and venetoclax is well tolerated and shows promise for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), according to initial results from the CLARITY feasibility trial.
Of 38 patients who received at least 6 months of treatment with combination ibrutinib (Imbruvica)/venetoclax (Venclexta) and reached month 8 – and therefore had computed tomography, clinical data, and peripheral blood and marrow assessments available – 15 (37%) achieved peripheral blood minimal residual disease (MRD) negativity, and 12 (32%) achieved bone marrow MRD negativity, Peter Hillmen, MBChB, PhD, reported during a press briefing at the annual meeting of the American Society of Hematology.
The rates of MRD negativity in the blood and marrow, and of normal trephine biopsy, were similar in subsets of patients who relapsed within 36 months of prior treatment with fludarabine/cyclophosphamide/rituximab (FCR) or bendamustine/rituximab (BR), and with prior idelalisib exposure, he noted.
“In terms of [International Workshop on Chronic Lymphocytic Leukemia] response criteria, which is a secondary endpoint, 47% of patients achieved a [complete remission or complete remission with incomplete hematologic recovery] and every patient has had an overall response, which for this group of patients is impressive,” he said.
Again, the findings were similar in those who were refractory to prior FCR/BR or to previous idelalisib, he noted.
Both ibrutinib and venetoclax are approved as single agents for the treatment of CLL. Ibrutinib is a Bruton’s tyrosine kinase inhibitor that has had a major effect on patient outcomes, showing overall survival advantages in numerous trials, Dr. Hillmen said.
“However, ibrutinib does not eradicate disease, and patients remain on treatment indefinitely or until progression,” he said.
Venetoclax is a highly selective B cell lymphoma–2 inhibitor approved for refractory CLL in patients with 17p deletion. It has a rapid effect, which can lead to tumor lysis syndrome, but also leads to eradication of MRD in some patients, which can lead to prolonged survival, he said.
The CLARITY trial was designed to investigate the safety and efficacy of the two in combination in relapsed/refractory CLL patients.
The primary endpoint of the study is MRD eradication in the marrow after 12 months of treatment. The current analysis looks at a key secondary endpoint of the study – MRD eradication in the marrow after 6 months of treatment.
The study enrolled 54 patients, including 37 men and 17 women with a median age of 64 years; 20% have 17p deletion, and the population was heavily pretreated, with 81% having prior FCR or BR (44% with relapse within 3 years of treatment), and 20% with previous idelalisib exposure. Patients were excluded if they had prior exposure to ibrutinib or venetoclax.
Treatment involves ibrutinib monotherapy at a dose of 420 mg/day for 2 months to debulk the disease, after which venetoclax is added at a dose escalating from 20 mg to 400 mg/day over 2 months to reduce the risk of tumor lysis syndrome.
Bone marrow biopsies are performed at 6, 12, and 24 months. Treatment is discontinued at 12 months in those who achieve MRD negativity at 6 months, and is discontinued at 24 months in those who achieve MRD negativity at 12 months.
The combination treatment was well tolerated in the first 38 patients. Bruising (mainly grade 1) occurred in 33 patients, and neutropenia (including 16 grade 3 cases and 6 grade 4 cases) occurred in 25, and some GI toxicity occurred, but was largely grade 1 or 2, Dr. Hillmen said.
“There really was otherwise very acceptable toxicity,” he added, noting that a single case of tumor lysis syndrome occurred, but was managed successfully by delaying venetoclax.
“That patient re-escalated back onto treatment and is doing well,” he said.
No patients stopped treatment, and only seven had treatment interruption, and then only for a few days, he noted.
The findings are encouraging, and suggest a potent synergy between ibrutinib and venetoclax, said Dr. Hillmen.
“We’re seeing, even at this very early stage, over 30% of patients achieving MRD negative remission, which was our target at the 12-month bone marrow stage with this combination,” he said.
In light of these results, the ongoing phase 3 FLAIR trial, which is actively recruiting, has been modified to include combination ibrutinib and venetoclax in front-line CLL, he said.
Dr. Hillmen reported financial relationships with AbbVie and several other pharmaceutical companies. The CLARITY trial is supported by AbbVie, Bloodwise, Experimental Cancer Medicine Centre, Janssen-Cilag, the National Institute for Health Research Clinical Research Network: Cancer, and the University of Birmingham (England).
[email protected]
SOURCE: Hillmen P et al., ASH abstract 428.
ATLANTA – Combination therapy with ibrutinib and venetoclax is well tolerated and shows promise for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL), according to initial results from the CLARITY feasibility trial.
Of 38 patients who received at least 6 months of treatment with combination ibrutinib (Imbruvica)/venetoclax (Venclexta) and reached month 8 – and therefore had computed tomography, clinical data, and peripheral blood and marrow assessments available – 15 (37%) achieved peripheral blood minimal residual disease (MRD) negativity, and 12 (32%) achieved bone marrow MRD negativity, Peter Hillmen, MBChB, PhD, reported during a press briefing at the annual meeting of the American Society of Hematology.
The rates of MRD negativity in the blood and marrow, and of normal trephine biopsy, were similar in subsets of patients who relapsed within 36 months of prior treatment with fludarabine/cyclophosphamide/rituximab (FCR) or bendamustine/rituximab (BR), and with prior idelalisib exposure, he noted.
“In terms of [International Workshop on Chronic Lymphocytic Leukemia] response criteria, which is a secondary endpoint, 47% of patients achieved a [complete remission or complete remission with incomplete hematologic recovery] and every patient has had an overall response, which for this group of patients is impressive,” he said.
Again, the findings were similar in those who were refractory to prior FCR/BR or to previous idelalisib, he noted.
Both ibrutinib and venetoclax are approved as single agents for the treatment of CLL. Ibrutinib is a Bruton’s tyrosine kinase inhibitor that has had a major effect on patient outcomes, showing overall survival advantages in numerous trials, Dr. Hillmen said.
“However, ibrutinib does not eradicate disease, and patients remain on treatment indefinitely or until progression,” he said.
Venetoclax is a highly selective B cell lymphoma–2 inhibitor approved for refractory CLL in patients with 17p deletion. It has a rapid effect, which can lead to tumor lysis syndrome, but also leads to eradication of MRD in some patients, which can lead to prolonged survival, he said.
The CLARITY trial was designed to investigate the safety and efficacy of the two in combination in relapsed/refractory CLL patients.
The primary endpoint of the study is MRD eradication in the marrow after 12 months of treatment. The current analysis looks at a key secondary endpoint of the study – MRD eradication in the marrow after 6 months of treatment.
The study enrolled 54 patients, including 37 men and 17 women with a median age of 64 years; 20% have 17p deletion, and the population was heavily pretreated, with 81% having prior FCR or BR (44% with relapse within 3 years of treatment), and 20% with previous idelalisib exposure. Patients were excluded if they had prior exposure to ibrutinib or venetoclax.
Treatment involves ibrutinib monotherapy at a dose of 420 mg/day for 2 months to debulk the disease, after which venetoclax is added at a dose escalating from 20 mg to 400 mg/day over 2 months to reduce the risk of tumor lysis syndrome.
Bone marrow biopsies are performed at 6, 12, and 24 months. Treatment is discontinued at 12 months in those who achieve MRD negativity at 6 months, and is discontinued at 24 months in those who achieve MRD negativity at 12 months.
The combination treatment was well tolerated in the first 38 patients. Bruising (mainly grade 1) occurred in 33 patients, and neutropenia (including 16 grade 3 cases and 6 grade 4 cases) occurred in 25, and some GI toxicity occurred, but was largely grade 1 or 2, Dr. Hillmen said.
“There really was otherwise very acceptable toxicity,” he added, noting that a single case of tumor lysis syndrome occurred, but was managed successfully by delaying venetoclax.
“That patient re-escalated back onto treatment and is doing well,” he said.
No patients stopped treatment, and only seven had treatment interruption, and then only for a few days, he noted.
The findings are encouraging, and suggest a potent synergy between ibrutinib and venetoclax, said Dr. Hillmen.
“We’re seeing, even at this very early stage, over 30% of patients achieving MRD negative remission, which was our target at the 12-month bone marrow stage with this combination,” he said.
In light of these results, the ongoing phase 3 FLAIR trial, which is actively recruiting, has been modified to include combination ibrutinib and venetoclax in front-line CLL, he said.
Dr. Hillmen reported financial relationships with AbbVie and several other pharmaceutical companies. The CLARITY trial is supported by AbbVie, Bloodwise, Experimental Cancer Medicine Centre, Janssen-Cilag, the National Institute for Health Research Clinical Research Network: Cancer, and the University of Birmingham (England).
[email protected]
SOURCE: Hillmen P et al., ASH abstract 428.
REPORTING FROM ASH 2017
Key clinical point:
Major finding: 37% and 32% of patients achieved peripheral blood and marrow MRD negativity, respectively.
Study details: Initial results from 38 patients in the CLARITY feasibility trial.
Disclosures: Dr. Hillmen reported financial relationships with AbbVie and several other pharmaceutical companies. The CLARITY trial is supported by AbbVie, Bloodwise, Experimental Cancer Medicine Centre, Janssen-Cilag, the National Institute for Health Research Clinical Research Network: Cancer, and the University of Birmingham.
Source: Hillmen P et al. ASH Abstract 428.
Late-breaking abstracts highlight treatment advances in CLL, myeloma, and more
.
In a preplanned interim analysis of data from 389 patients in the randomized phase III Murano trial, venetoclax and rituximab therapy proved “superior to the standard of care and well tolerated, and a major advance in the management of [relapsed/refractory] CLL,” ASH President Kenneth C. Anderson, MD said during a premeeting preview session for the media.
In Murano, venetoclax plus rituximab bettered bendamustine plus rituximab in progression-free survival, overall survival, overall and complete response rates, and number of patients achieving minimal residual disease (MRD) negativity, said Dr. Anderson, who is also director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute, Boston.
The results were consistent in all risk subsets, including patients who had high-risk disease by virtue of chromosome 17p deletion, according Dr. Anderson.
In another late-breaking randomized phase III study, known as ALCYONE, adding the CD38-targeting monoclonal antibody daratumumab to standard therapy with bortezomib, melphalan, and prednisone (VMP) resulted in a “doubling” of progression-free survival in patients who had newly diagnosed multiple myeloma and were ineligible for transplantation, he reported.
In the trial of more than 700 patients, daratumumab plus VMP as initial treatment for nontransplant patients was well tolerated and improved outcomes, including overall response rate and the percent of patients who achieved MRD negative status.
“As we saw in CLL, so it’s true in this abstract in myeloma: this is a very major advance,” Dr. Anderson said.
Also during the preview session, ASH Secretary Robert A. Brodsky, MD, discussed the randomized, phase III HERCULES study results, which showed that patients with acquired thrombotic thrombocytopenic purpura (TTP) may benefit when caplacizumab is added to standard therapy. Caplacizumab targets the A1 domain of von Willebrand factor, which inhibits interaction between ultra-large von Willebrand factor and platelets.
In the trial, 145 patients were randomized to receive either plasma exchange alone or plasma exchange and caplacizumab.
Preliminary results suggest “this was a very positive trial” with a primary endpoint of time to platelet response that “greatly favored the caplacizumab arm,” said Dr. Brodsky, professor of medicine and oncology and director of the division of hematology at Johns Hopkins University, Baltimore. “Even the secondary composite endpoint of death, recurrence, and/or major thromboembolic events was much improved with caplacizumab, so this is a very positive trial and potentially a game-changing drug for the management of TTP, which can be very challenging.”
Dr. Brodsky also discussed the Hokusai VTE-Cancer Study, a randomized, open-label, blinded outcome assessment trial that showed the oral factor Xa inhibitor edoxaban was noninferior to subcutaneous dalteparin for the prevention of cancer-associated venous thromboembolism.
With more than 1,000 patients enrolled in 114 centers, the Hokusai VTE-Cancer Study had a primary outcome of the composite of the first recurrent VTE or major bleeding event during follow-up. The primary outcome occurred in 12.8% of patients in the edoxaban group, compared with 13.5% of patients in the dalteparin group (P = .0056 for noninferiority), according to the preliminary published results.
The key question addressed by the trial is whether a newer oral anticoagulant, edoxaban, can substitute for the older, subcutaneously administered low-molecular-weight heparin, dalteparin. The results “confirmed that a newer oral anticoagulant is at least as good and as safe as the low molecular weight heparin,” allowing patients the convenience of an oral therapy, Dr. Brodsky noted.
This year’s late-breaking abstracts at ASH are:
LBA-1 Results of the Randomized, Double-Blind, Placebo-Controlled, Phase III Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura.
LBA-2 Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase III Murano Study.
LBA-3 Mutations in SRP54 Gene Cause Severe Primary Neutropenia As Well As Shwachman-Diamond-like Syndrome.
LBA-4 Phase III Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE).
LBA-5 Prospective Molecular MRD Detection By NGS: A Powerful Independent Predictor for Relapse and Survival in Adults with Newly Diagnosed AML.
LBA-6 A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study
.
In a preplanned interim analysis of data from 389 patients in the randomized phase III Murano trial, venetoclax and rituximab therapy proved “superior to the standard of care and well tolerated, and a major advance in the management of [relapsed/refractory] CLL,” ASH President Kenneth C. Anderson, MD said during a premeeting preview session for the media.
In Murano, venetoclax plus rituximab bettered bendamustine plus rituximab in progression-free survival, overall survival, overall and complete response rates, and number of patients achieving minimal residual disease (MRD) negativity, said Dr. Anderson, who is also director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute, Boston.
The results were consistent in all risk subsets, including patients who had high-risk disease by virtue of chromosome 17p deletion, according Dr. Anderson.
In another late-breaking randomized phase III study, known as ALCYONE, adding the CD38-targeting monoclonal antibody daratumumab to standard therapy with bortezomib, melphalan, and prednisone (VMP) resulted in a “doubling” of progression-free survival in patients who had newly diagnosed multiple myeloma and were ineligible for transplantation, he reported.
In the trial of more than 700 patients, daratumumab plus VMP as initial treatment for nontransplant patients was well tolerated and improved outcomes, including overall response rate and the percent of patients who achieved MRD negative status.
“As we saw in CLL, so it’s true in this abstract in myeloma: this is a very major advance,” Dr. Anderson said.
Also during the preview session, ASH Secretary Robert A. Brodsky, MD, discussed the randomized, phase III HERCULES study results, which showed that patients with acquired thrombotic thrombocytopenic purpura (TTP) may benefit when caplacizumab is added to standard therapy. Caplacizumab targets the A1 domain of von Willebrand factor, which inhibits interaction between ultra-large von Willebrand factor and platelets.
In the trial, 145 patients were randomized to receive either plasma exchange alone or plasma exchange and caplacizumab.
Preliminary results suggest “this was a very positive trial” with a primary endpoint of time to platelet response that “greatly favored the caplacizumab arm,” said Dr. Brodsky, professor of medicine and oncology and director of the division of hematology at Johns Hopkins University, Baltimore. “Even the secondary composite endpoint of death, recurrence, and/or major thromboembolic events was much improved with caplacizumab, so this is a very positive trial and potentially a game-changing drug for the management of TTP, which can be very challenging.”
Dr. Brodsky also discussed the Hokusai VTE-Cancer Study, a randomized, open-label, blinded outcome assessment trial that showed the oral factor Xa inhibitor edoxaban was noninferior to subcutaneous dalteparin for the prevention of cancer-associated venous thromboembolism.
With more than 1,000 patients enrolled in 114 centers, the Hokusai VTE-Cancer Study had a primary outcome of the composite of the first recurrent VTE or major bleeding event during follow-up. The primary outcome occurred in 12.8% of patients in the edoxaban group, compared with 13.5% of patients in the dalteparin group (P = .0056 for noninferiority), according to the preliminary published results.
The key question addressed by the trial is whether a newer oral anticoagulant, edoxaban, can substitute for the older, subcutaneously administered low-molecular-weight heparin, dalteparin. The results “confirmed that a newer oral anticoagulant is at least as good and as safe as the low molecular weight heparin,” allowing patients the convenience of an oral therapy, Dr. Brodsky noted.
This year’s late-breaking abstracts at ASH are:
LBA-1 Results of the Randomized, Double-Blind, Placebo-Controlled, Phase III Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura.
LBA-2 Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase III Murano Study.
LBA-3 Mutations in SRP54 Gene Cause Severe Primary Neutropenia As Well As Shwachman-Diamond-like Syndrome.
LBA-4 Phase III Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE).
LBA-5 Prospective Molecular MRD Detection By NGS: A Powerful Independent Predictor for Relapse and Survival in Adults with Newly Diagnosed AML.
LBA-6 A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study
.
In a preplanned interim analysis of data from 389 patients in the randomized phase III Murano trial, venetoclax and rituximab therapy proved “superior to the standard of care and well tolerated, and a major advance in the management of [relapsed/refractory] CLL,” ASH President Kenneth C. Anderson, MD said during a premeeting preview session for the media.
In Murano, venetoclax plus rituximab bettered bendamustine plus rituximab in progression-free survival, overall survival, overall and complete response rates, and number of patients achieving minimal residual disease (MRD) negativity, said Dr. Anderson, who is also director of the Lebow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute, Boston.
The results were consistent in all risk subsets, including patients who had high-risk disease by virtue of chromosome 17p deletion, according Dr. Anderson.
In another late-breaking randomized phase III study, known as ALCYONE, adding the CD38-targeting monoclonal antibody daratumumab to standard therapy with bortezomib, melphalan, and prednisone (VMP) resulted in a “doubling” of progression-free survival in patients who had newly diagnosed multiple myeloma and were ineligible for transplantation, he reported.
In the trial of more than 700 patients, daratumumab plus VMP as initial treatment for nontransplant patients was well tolerated and improved outcomes, including overall response rate and the percent of patients who achieved MRD negative status.
“As we saw in CLL, so it’s true in this abstract in myeloma: this is a very major advance,” Dr. Anderson said.
Also during the preview session, ASH Secretary Robert A. Brodsky, MD, discussed the randomized, phase III HERCULES study results, which showed that patients with acquired thrombotic thrombocytopenic purpura (TTP) may benefit when caplacizumab is added to standard therapy. Caplacizumab targets the A1 domain of von Willebrand factor, which inhibits interaction between ultra-large von Willebrand factor and platelets.
In the trial, 145 patients were randomized to receive either plasma exchange alone or plasma exchange and caplacizumab.
Preliminary results suggest “this was a very positive trial” with a primary endpoint of time to platelet response that “greatly favored the caplacizumab arm,” said Dr. Brodsky, professor of medicine and oncology and director of the division of hematology at Johns Hopkins University, Baltimore. “Even the secondary composite endpoint of death, recurrence, and/or major thromboembolic events was much improved with caplacizumab, so this is a very positive trial and potentially a game-changing drug for the management of TTP, which can be very challenging.”
Dr. Brodsky also discussed the Hokusai VTE-Cancer Study, a randomized, open-label, blinded outcome assessment trial that showed the oral factor Xa inhibitor edoxaban was noninferior to subcutaneous dalteparin for the prevention of cancer-associated venous thromboembolism.
With more than 1,000 patients enrolled in 114 centers, the Hokusai VTE-Cancer Study had a primary outcome of the composite of the first recurrent VTE or major bleeding event during follow-up. The primary outcome occurred in 12.8% of patients in the edoxaban group, compared with 13.5% of patients in the dalteparin group (P = .0056 for noninferiority), according to the preliminary published results.
The key question addressed by the trial is whether a newer oral anticoagulant, edoxaban, can substitute for the older, subcutaneously administered low-molecular-weight heparin, dalteparin. The results “confirmed that a newer oral anticoagulant is at least as good and as safe as the low molecular weight heparin,” allowing patients the convenience of an oral therapy, Dr. Brodsky noted.
This year’s late-breaking abstracts at ASH are:
LBA-1 Results of the Randomized, Double-Blind, Placebo-Controlled, Phase III Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura.
LBA-2 Venetoclax Plus Rituximab Is Superior to Bendamustine Plus Rituximab in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia - Results from Pre-Planned Interim Analysis of the Randomized Phase III Murano Study.
LBA-3 Mutations in SRP54 Gene Cause Severe Primary Neutropenia As Well As Shwachman-Diamond-like Syndrome.
LBA-4 Phase III Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE).
LBA-5 Prospective Molecular MRD Detection By NGS: A Powerful Independent Predictor for Relapse and Survival in Adults with Newly Diagnosed AML.
LBA-6 A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study
FROM ASH 2017