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CHICAGO – The combination of pomalidomide and low-dose dexamethasone is superior to high-dose dexamethasone monotherapy for treating patients with relapsed and refractory multiple myeloma, based on updated results from the multicenter, randomized MM-003 trial.
Among the 455 patients studied in the trial, those assigned to the combination therapy had a 52% lower risk of progression or death and a 26% lower risk of death alone when compared with peers assigned to single-agent high-dose dexamethasone.
The two regimens had much the same toxicity profile, although the combination was associated with a higher rate of grade 3/4 hematologic toxicity.
"Pomalidomide in combination with low-dose dexamethasone should be considered as a new standard of care for treatment of relapsed and refractory multiple myeloma patients after treatment with lenalidomide and bortezomib," presenting author Dr. Katja C. Weisel commented at the annual meeting of the American Society of Clinical Oncology.
All of the patients enrolled in the MM-003 trial had received at least two prior therapies and had disease refractory to their last therapy, according to Dr. Weisel, a hematologist-oncologist with the University Hospital Tübingen, Germany. All had experienced a failure of both Millennium’s bortezomib (Velcade) and Celgene’s lenalidomide (Revlimid).
The patients were randomized 2:1 to receive low-dose dexamethasone plus Celgene’s pomalidomide (Pomalyst), an antiangiogenic and immune-modulating agent, or high-dose dexamethasone alone. Patients given pomalidomide or who had a history of deep vein thrombosis were given thromboprophylaxis.
Patients who experienced progression on high-dose dexamethasone entered the companion MM-003C trial, in which they were given pomalidomide.
Initial trial results after a median follow-up of 4 months, which were previously reported, showed there were significantly better progression-free survival and overall survival with the combination. These results led to a recommendation by the trial’s monitoring committee that all patients in the high-dose dexamethasone group be given access to pomalidomide regardless of whether they had progression. In all, half of the patients in that group received pomalidomide after high-dose dexamethasone due to either this recommendation or entry into the companion trial.
In the updated analysis, now with a median follow-up of 10 months, progression-free survival was still significantly better with pomalidomide plus low-dose dexamethasone than with high-dose dexamethasone (4.0 vs. 1.9 months; hazard ratio, 0.48; P less than .001).
Overall survival was also still significantly better with the combination (12.7 vs. 8.1 months; HR, 0.74; P = .028).
"This overall survival benefit was maintained despite a high crossover rate, in 50% of the patients. ... In addition, all patients who were still alive at this time in the high-dose dexamethasone group had received pomalidomide as a salvage treatment," Dr. Weisel noted.
The progression-free survival and overall survival benefits were generally similar across subgroups of patients whose disease was refractory to both lenalidomide and bortezomib, who had received lenalidomide as their last prior therapy, and who had received bortezomib as their last prior therapy.
"The safety profile of pomalidomide is predictable and manageable, and the drug with its oral application is generally well tolerated in this heavily pretreated patient group," Dr. Weisel commented.
The main toxicity with the combination was hematologic toxicity: The rate of grade 3/4 neutropenia was 48% with the combination, compared with 16% with high-dose dexamethasone. The combination group and the high-dose dexamethasone group had essentially the same rates of grade 3/4 deep vein thrombosis and pulmonary embolism (1% and 0%, respectively), peripheral neuropathy (1% and 1%), and discontinuation due to adverse events (9% and 10%).
Dr. Weisel disclosed that she is a consultant to and receives honoraria from Celgene and Janssen.
The median progression-free survival in patients who achieved a minimal response (MR) of 8 months was about the same as the 7 months seen in patients who achieved a partial response or better.
When you don’t have many options left, even something like an MR can carry significant clinical benefit. And the important message in my mind here is that if you don’t get a PR (partial response) or you don’t get a CR (complete response), don’t throw the therapy away. These minor benefits may actually translate into significant long-term clinical benefits, and it’s a different situation than we are discussing in the context of a newly diagnosed, treatment-naive patient, where our goal ultimately should be a CR.
Also, despite the clear survival benefit of the combination, there was a late crossing of the overall survival curves in favor of high-dose dexamethasone. If you look at the number of patients who stayed on high-dose dexamethasone, it was vanishingly small. So I think that late improvement in survival was a consequence of getting the better therapy as part of the crossover design.
Dr. Sagar Lonial, of the Winship Cancer Institute, Emory University, Atlanta, was the invited discussant of the study. Dr. Lonial disclosed that he is a consultant to and receives research funding from Bristol-Myers Squibb, Celgene, Millennium, and Novartis, and also is a consultant to Onyx.
The median progression-free survival in patients who achieved a minimal response (MR) of 8 months was about the same as the 7 months seen in patients who achieved a partial response or better.
When you don’t have many options left, even something like an MR can carry significant clinical benefit. And the important message in my mind here is that if you don’t get a PR (partial response) or you don’t get a CR (complete response), don’t throw the therapy away. These minor benefits may actually translate into significant long-term clinical benefits, and it’s a different situation than we are discussing in the context of a newly diagnosed, treatment-naive patient, where our goal ultimately should be a CR.
Also, despite the clear survival benefit of the combination, there was a late crossing of the overall survival curves in favor of high-dose dexamethasone. If you look at the number of patients who stayed on high-dose dexamethasone, it was vanishingly small. So I think that late improvement in survival was a consequence of getting the better therapy as part of the crossover design.
Dr. Sagar Lonial, of the Winship Cancer Institute, Emory University, Atlanta, was the invited discussant of the study. Dr. Lonial disclosed that he is a consultant to and receives research funding from Bristol-Myers Squibb, Celgene, Millennium, and Novartis, and also is a consultant to Onyx.
The median progression-free survival in patients who achieved a minimal response (MR) of 8 months was about the same as the 7 months seen in patients who achieved a partial response or better.
When you don’t have many options left, even something like an MR can carry significant clinical benefit. And the important message in my mind here is that if you don’t get a PR (partial response) or you don’t get a CR (complete response), don’t throw the therapy away. These minor benefits may actually translate into significant long-term clinical benefits, and it’s a different situation than we are discussing in the context of a newly diagnosed, treatment-naive patient, where our goal ultimately should be a CR.
Also, despite the clear survival benefit of the combination, there was a late crossing of the overall survival curves in favor of high-dose dexamethasone. If you look at the number of patients who stayed on high-dose dexamethasone, it was vanishingly small. So I think that late improvement in survival was a consequence of getting the better therapy as part of the crossover design.
Dr. Sagar Lonial, of the Winship Cancer Institute, Emory University, Atlanta, was the invited discussant of the study. Dr. Lonial disclosed that he is a consultant to and receives research funding from Bristol-Myers Squibb, Celgene, Millennium, and Novartis, and also is a consultant to Onyx.
CHICAGO – The combination of pomalidomide and low-dose dexamethasone is superior to high-dose dexamethasone monotherapy for treating patients with relapsed and refractory multiple myeloma, based on updated results from the multicenter, randomized MM-003 trial.
Among the 455 patients studied in the trial, those assigned to the combination therapy had a 52% lower risk of progression or death and a 26% lower risk of death alone when compared with peers assigned to single-agent high-dose dexamethasone.
The two regimens had much the same toxicity profile, although the combination was associated with a higher rate of grade 3/4 hematologic toxicity.
"Pomalidomide in combination with low-dose dexamethasone should be considered as a new standard of care for treatment of relapsed and refractory multiple myeloma patients after treatment with lenalidomide and bortezomib," presenting author Dr. Katja C. Weisel commented at the annual meeting of the American Society of Clinical Oncology.
All of the patients enrolled in the MM-003 trial had received at least two prior therapies and had disease refractory to their last therapy, according to Dr. Weisel, a hematologist-oncologist with the University Hospital Tübingen, Germany. All had experienced a failure of both Millennium’s bortezomib (Velcade) and Celgene’s lenalidomide (Revlimid).
The patients were randomized 2:1 to receive low-dose dexamethasone plus Celgene’s pomalidomide (Pomalyst), an antiangiogenic and immune-modulating agent, or high-dose dexamethasone alone. Patients given pomalidomide or who had a history of deep vein thrombosis were given thromboprophylaxis.
Patients who experienced progression on high-dose dexamethasone entered the companion MM-003C trial, in which they were given pomalidomide.
Initial trial results after a median follow-up of 4 months, which were previously reported, showed there were significantly better progression-free survival and overall survival with the combination. These results led to a recommendation by the trial’s monitoring committee that all patients in the high-dose dexamethasone group be given access to pomalidomide regardless of whether they had progression. In all, half of the patients in that group received pomalidomide after high-dose dexamethasone due to either this recommendation or entry into the companion trial.
In the updated analysis, now with a median follow-up of 10 months, progression-free survival was still significantly better with pomalidomide plus low-dose dexamethasone than with high-dose dexamethasone (4.0 vs. 1.9 months; hazard ratio, 0.48; P less than .001).
Overall survival was also still significantly better with the combination (12.7 vs. 8.1 months; HR, 0.74; P = .028).
"This overall survival benefit was maintained despite a high crossover rate, in 50% of the patients. ... In addition, all patients who were still alive at this time in the high-dose dexamethasone group had received pomalidomide as a salvage treatment," Dr. Weisel noted.
The progression-free survival and overall survival benefits were generally similar across subgroups of patients whose disease was refractory to both lenalidomide and bortezomib, who had received lenalidomide as their last prior therapy, and who had received bortezomib as their last prior therapy.
"The safety profile of pomalidomide is predictable and manageable, and the drug with its oral application is generally well tolerated in this heavily pretreated patient group," Dr. Weisel commented.
The main toxicity with the combination was hematologic toxicity: The rate of grade 3/4 neutropenia was 48% with the combination, compared with 16% with high-dose dexamethasone. The combination group and the high-dose dexamethasone group had essentially the same rates of grade 3/4 deep vein thrombosis and pulmonary embolism (1% and 0%, respectively), peripheral neuropathy (1% and 1%), and discontinuation due to adverse events (9% and 10%).
Dr. Weisel disclosed that she is a consultant to and receives honoraria from Celgene and Janssen.
CHICAGO – The combination of pomalidomide and low-dose dexamethasone is superior to high-dose dexamethasone monotherapy for treating patients with relapsed and refractory multiple myeloma, based on updated results from the multicenter, randomized MM-003 trial.
Among the 455 patients studied in the trial, those assigned to the combination therapy had a 52% lower risk of progression or death and a 26% lower risk of death alone when compared with peers assigned to single-agent high-dose dexamethasone.
The two regimens had much the same toxicity profile, although the combination was associated with a higher rate of grade 3/4 hematologic toxicity.
"Pomalidomide in combination with low-dose dexamethasone should be considered as a new standard of care for treatment of relapsed and refractory multiple myeloma patients after treatment with lenalidomide and bortezomib," presenting author Dr. Katja C. Weisel commented at the annual meeting of the American Society of Clinical Oncology.
All of the patients enrolled in the MM-003 trial had received at least two prior therapies and had disease refractory to their last therapy, according to Dr. Weisel, a hematologist-oncologist with the University Hospital Tübingen, Germany. All had experienced a failure of both Millennium’s bortezomib (Velcade) and Celgene’s lenalidomide (Revlimid).
The patients were randomized 2:1 to receive low-dose dexamethasone plus Celgene’s pomalidomide (Pomalyst), an antiangiogenic and immune-modulating agent, or high-dose dexamethasone alone. Patients given pomalidomide or who had a history of deep vein thrombosis were given thromboprophylaxis.
Patients who experienced progression on high-dose dexamethasone entered the companion MM-003C trial, in which they were given pomalidomide.
Initial trial results after a median follow-up of 4 months, which were previously reported, showed there were significantly better progression-free survival and overall survival with the combination. These results led to a recommendation by the trial’s monitoring committee that all patients in the high-dose dexamethasone group be given access to pomalidomide regardless of whether they had progression. In all, half of the patients in that group received pomalidomide after high-dose dexamethasone due to either this recommendation or entry into the companion trial.
In the updated analysis, now with a median follow-up of 10 months, progression-free survival was still significantly better with pomalidomide plus low-dose dexamethasone than with high-dose dexamethasone (4.0 vs. 1.9 months; hazard ratio, 0.48; P less than .001).
Overall survival was also still significantly better with the combination (12.7 vs. 8.1 months; HR, 0.74; P = .028).
"This overall survival benefit was maintained despite a high crossover rate, in 50% of the patients. ... In addition, all patients who were still alive at this time in the high-dose dexamethasone group had received pomalidomide as a salvage treatment," Dr. Weisel noted.
The progression-free survival and overall survival benefits were generally similar across subgroups of patients whose disease was refractory to both lenalidomide and bortezomib, who had received lenalidomide as their last prior therapy, and who had received bortezomib as their last prior therapy.
"The safety profile of pomalidomide is predictable and manageable, and the drug with its oral application is generally well tolerated in this heavily pretreated patient group," Dr. Weisel commented.
The main toxicity with the combination was hematologic toxicity: The rate of grade 3/4 neutropenia was 48% with the combination, compared with 16% with high-dose dexamethasone. The combination group and the high-dose dexamethasone group had essentially the same rates of grade 3/4 deep vein thrombosis and pulmonary embolism (1% and 0%, respectively), peripheral neuropathy (1% and 1%), and discontinuation due to adverse events (9% and 10%).
Dr. Weisel disclosed that she is a consultant to and receives honoraria from Celgene and Janssen.
AT THE ASCO ANNUAL MEETING 2013
Major finding: Compared with high-dose dexamethasone, pomalidomide plus low-dose dexamethasone yielded better median progression-free survival (4.0 vs. 1.9 months) and overall survival (12.7 vs. 8.1 months).
Data source: A phase III, multicenter, randomized open-label trial of 455 patients with relapsed and refractory multiple myeloma (MM-003 trial).
Disclosures: Dr. Weisel disclosed that she is a consultant to and receives honoraria from Janssen and Celgene, the maker of pomalidomide.
