Support for the oral immunomodulatory agent pomalidomide for multiple myeloma took a step forward when the phase III MM-003 trial showed a survival advantage in patients with advanced disease, in addition to a doubling in progression-free survival, when pomalidomide was given with low-dose dexamethasone.
The data for the open-label phase III MM-003 trial of 455 patients with relapsed or refractory myeloma were reported at the 54th Annual Meeting of the American Society of Hematology by Meletios A. Dimopoulos, MD, Professor and Chairman of the Department of Clinical Therapeutics at Alexandra Hospital in Athens, Greece.1
The study crossed the prespecified superiority boundary at the interim analysis. Therefore, the Data Safety Monitoring Board recommended that the single-agent dexamethasone arm be discontinued and patients crossed over to receive the novel combination.
“We saw a statistically significant increase in progression-free survival from about 2 months with high-dose dexamethasone to 4 months with this combination, and this difference translated to a significant overall survival advantage as well,” he said.
“The benefit of pomalidomide plus low-dose dexamethasone has now been shown in the context of a prospective randomized trial, and it is superior to the current standard of care in patients with relapsed/refractory myeloma,” he maintained.
Pomalidomide is considered more potent than the other available immunomodulatory drugs, thalidomide (Thalomid) and lenalidomide (Revlimid). Trials in the first-line setting are now underway, and pomalidomide is under consideration for approval by the FDA.
Overall Survival Benefit Observed
After a median follow-up of 18 months, the median progression-free survival was 15.7 weeks with pomalidomide at 4 mg plus low-dose dexamethasone at 20 mg vs 8 weeks with single-agent high-dose dexamethasone (20 mg administered more frequently), which was a 55% reduction in risk (P < .001).
While median overall survival was 34 weeks with high-dose dexamethasone, it has not been reached with pomalidomide/low-dose dexamethasone. This yielded a 47% risk reduction for mortality (P < .001), and Dr. Dimopoulos projected that the average patient would be alive for about 1 year.
Good tolerability was observed in patients receiving the combination, with side effects occurring as expected. The greatest difference in tolerability from the single agent was a higher incidence of neutropenia with the combination (42% vs 15%). But the incidence of infection was similar in both arms of the study.
At the time of the analysis, 45% of patients on the combination arm and 25% in the single-agent arm remained on study. More of the high-dose dexamethasone arm discontinued the regimen due to disease progression (48% vs 35%).
“We believe this study provides the basis for considering this combination as a new standard of care for hard-to-treat patients who have exhausted most standard treatments for their refractory disease,” Dr. Dimopoulos stated. “And we believe pomalidomide may offer even greater benefit if studied among less heavily treated patients.” ■
Disclosure: Dr. Dimopoulos has received honoraria from Celgene.
1. Dimopoulos MA, Lacy MQ, Moreau P, et al: Pomalidomide in combination with low-dose dexamethasone demonstrates a significant progression-free survival and overall survival advantage in relapsed/refractory multiple myeloma: A phase 3, multicenter, randomized, open-label study. 2012 ASH Annual Meeting. Abstract LBA-6. Presented December 11, 2012.
Shaji K. Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, commented on the findings. “Patients with myeloma are living longer, but the disease comes back in the majority. We really need new drugs, and I think the main message of this study is that clearly patients do live longer on this...