Pomalidomide (Pomalyst) plus low-dose dexamethasone significantly improved progression-free survival compared to pomalidomide alone in patients with relapsed and refractory multiple myeloma enrolled in a multicenter, open-label study, the phase II part of the MM-002 trial. The study confirmed the synergistic activity of pomalidomide combined with low-dose dexamethasone, and the combination therapy “provides an important new treatment option for [relapsed/refractory multiple myeloma] patients who have received multiple prior therapies,” reported Paul G. Richardson, MD, of Dana-Farber Cancer Institute, Boston, and colleagues in Blood.
Patients in the trial had received two or more prior therapies (median, 5; range, 1–13), including lenalidomide (Revlimid) and bortezomib (Velcade), and had shown disease progression within 60 days of their last therapy. A total of 221 patients from 18 centers in the United States and Canada were randomly assigned to 4 mg/day of pomalidomide on days 1 to 21 of each 28-day cycle plus low-dose dexamethasone (40 mg/week)(n = 113) or pomalidomide alone (n = 108). The median age of patients was 63 years, 81% were white, 54% were male, and 27% had high-risk cytogenetics.
At a median follow-up of 14.2 months, median progression-free survival, the primary endpoint of the trial, was 4.2 months for pomalidomide plus low-dose dexamethasone vs 2.7 months for pomalidomide alone (hazard ratio = 0.68, P = .003).
The respective overall response rates were 33% and 18% (P = .013). Median response durations were 8.3 months for pomalidomide plus low-dose dexamethasone and 10.7 months for pomalidomide alone. Median overall survival in the intent-to-treat population was 16.5 for pomalidomide plus low-dose dexamethasone and 13.7 months with pomalidomide alone, “which compares favorably with historically reported 9-month survival rates for patients in whom currently approved novel therapies have failed,” the investigators noted.
Refractoriness to lenalidomide or resistance to both lenalidomide and bortezomib did not affect outcomes with pomalidomide and low-dose dexamethasone. The investigators noted a limited cross-resistance between pomalidomide and lenalidomide, which “supports the effectiveness of sequential use of immunomodulatory drugs, as well as combinations.” They added, “There is a clear unmet need for new treatments, particularly for patients who are relapsed and refractory to novel agents.”
Patients with cytogenetic abnormalities had an overall response rate of 23% and median response duration of 4.9 months with the combination therapy, “suggesting encouraging activity in patients with high-risk cytogenetic profiles and poor prognosis,” the authors stated.
The most common grade 3/4 adverse event was neutropenia, occurring in 41% of patients receiving combination therapy and 48% of those receiving pomalidomide alone. No grade 3/4 peripheral neuropathy was reported.
“With appropriate management, the rates of discontinuations due to treatment-related [adverse events] were low [2%–3%],” the researchers reported. A total of 19 deaths occurred during the study period, 10 among patients receiving combination therapy and 9 among those receiving pomalidomide alone, with most deaths attributed to multiple myeloma and disease progression.
Richardson PG, et al: Blood. January 13, 2014 (early release online).