Atlanta, GA—Support for the oral immunomodulatory agent pomalidomide for the treatment of multiple myeloma took a giant step forward when new data from the phase 3 MM-003 trial showed a survival advantage in patients with advanced disease.
The data were reported at the 2012 American Society of Hematology meeting by Meletios Dimopoulos, MD, Professor and Chairman of the Department of Clinical Therapeutics at Alexandra Hospital in Athens, Greece.
In this open-label, phase 3 trial of 455 patients, pomalidomide 4 mg, in combination with low-dose dexamethasone, significantly improved progression-free survival (PFS) as well as overall survival (OS) compared with high-dose dexamethasone alone, Dr Dimopoulos reported in a late-breaking abstract.
In patients with relapsed and/or refractory myeloma, treatment with the combination of pomalidomide and low-dose dexamethasone essentially doubled the PFS time compared with high-dose dexamethasone alone.
“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,” Dr Dimopoulos 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.”
Pomalidomide is considered more potent than the other available immunomodulatory drugs, thalidomide and lenalidomide. A New Drug Application for pomalidomide has been accepted for review by the US Food and Drug Administration. The Prescription Drug User Fee Act date is February 10, 2013.
Significant Overall Survival Benefit
After a median follow-up of 18 months, the median PFS was 15.7 weeks with the pomalidomide plus low-dose dexamethasone combination versus 8 weeks with high-dose dexamethasone as a single agent, a 55% reduction in risk (P <.001).
Although median OS was 34 weeks with high-dose dexamethasone, it has not been reached with pomalidomide plus low-dose dexamethasone. So far, this translates into a 47% risk reduction (P <.001).
“We expect median overall survival with the combination to be around 11 or 12 months,” Dr Dimopoulos noted.
The Data Safety and Monitoring Board, therefore, recommended that the monotherapy arm subsequently receive the combination as a result of its high efficacy.
The combination was well tolerated, and toxicities were as expected. Primarily, neutropenia was more common in the combination arm with pomalidomide than in the high-dose dexamethasone alone arm (42% vs 15%, respectively).
At the time of the analysis, 45% of patients in the combination arm and 25% in the monotherapy arm remained in the study, with more patients receiving high-dose dexamethasone discontinuing because of disease progression than patients receiving pomalidomide plus low-dose dexamethasone (48% vs 35%, respectively).
“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 added. “And we believe pomalidomide may offer even greater benefit if studied among less heavily treated patients as a first-line therapy.”
Clinical trials with pomalidomide in the first-line setting are now under way, Dr Dimopoulos said.