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.
Dr. Katja C. Weisel
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.