ATLANTA—Pomalidomide plus low-dose dexamethasone significantly improved progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory multiple myeloma vs high-dose dexamethasone alone and “should be considered as a new treatment option for these patients” who have exhausted lenalidomide and bortezomib, a study presented during the 54th American Society of Hematology Annual Meeting and Exposition recommended.

Patients who are refractory to both lenalidomide and bortezomib “currently have no treatment options outside of clinical trials and high-dose dexamethasone is a common salvage therapy,” said Meletios A. Dimopoulos, MD, of Alexandra Hospital, Athens, Greece, and colleagues.

The global phase 3, multicenter, open-label study is the first randomized trial to evaluate  pomalidomide plus low-dose dexamethasone vs high-dose dexamethasone alone in patients “double refractory” to both lenalidomide and bortezomib.

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Between March 2011 and September 2012, 455 patients were randomly assigned 2:1 to pomalidomide 4mg days 1-21 and dexamethasone 40mg (20mg for patients >75 years of age) on days 1, 8, 15, and 22 in a 28-day cycle (arm A; n=302) or dexamethasone 40mg (20mg for patients >75 years of age) alone on days 1-4, 9-12, and 17-20 in a 28-day cycle (arm B; n=153).

Patients were stratified by age (≤75 vs >75 years), disease population (refractory vs refractory and relapsed vs refractory and intolerant [intolerant to bortezomib only]), and number of prior therapies (2 vs >2). Median number of prior therapies was 5 (range, 1-17), with 72% of patients refractory to both lenalidomide and bortezomib. At the time of analysis, 45% of patients in arm A and 25% in arm B remained on study.

Median PFS was significantly longer with pomalidomide plus low-dose dexamethasone, 3.6 months, vs high-dose dexamethasone alone, 1.8 months (HR 0.45; P<0.001).

OS was also significantly longer with pomalidomide + low-dose dexamethasone (which included 45 patients who received pomalidomide after progressing on high-dose dexamethasone) vs high-dose dexamethasone alone, Dr. Dimopoulos reported. Median OS was not reached vs 7.8 months, respectively (HR 0.53; P<0.001).

As of November 9, 2012, ongoing evaluation of response by an independent review adjudication committee in the intent-to-treat population showed an overall response rate of 24% in the pomalidomide plus low-dose dexamethasone arm vs 3% in the high-dose dexamethasone arm (P<0.001).

Overall, 25% of patients in arm A and 38% in arm B died; progressive disease and infections were the primary causes. Frequent grade 3/4 hematologic toxicities included neutropenia (42% in arm A vs 15% in arm B), thrombocytopenia (21% vs 24%), and febrile neutropenia (7% vs 0%). Other toxicities (grade 3/4) were predominantly infections, hemorrhage, glucose intolerance, peripheral neuropathy, and venous thromboembolism. The primary reason for treatment discontinuation was progressive disease, occurring in rates of 35% in arm A and 49% in arm B.