Pomalidomide in Multiple Myeloma Patients

Atlanta—Patients with multiple myeloma who had primary refractory or relapsed and refractory disease had a significant improvement in progression-free and overall survival if they took pomalidomide plus low-dose dexamethasone compared with a group that received high-dose dexamethasone, according to a phase 3, prospective, randomized, open-label trial.

The combination group had a median progression-free survival of 3.6 months compared with 1.8 months for the high-dose dexamethasone group (hazard ratio [HR], 0.45; P<.001). Median overall survival was not reached in the combination group and was 7.8 months (HR, 0.53; P<.001) in the high-dose dexamethasone group.

Meletios A. Dimopoulos, MD, the study’s lead author and chairman of the department of clinical therapeutics at University Athens School of Medicine in Athens, Greece, presented the results in a late-breaking abstract session at the ASH meeting.

Dr. Dimopoulos said many patients with double refractory multiple myeloma are treated with high-dose dexamethasone, although there is no standard therapeutic option. Previous trials showed pomalidomide and low-dose dexamethasone were effective in relapsed or refractory multiple myeloma patients who received lenalidomide and/or bortezomib.

This is the first study to evaluate pomalidomide and low-dose dexamethasone versus high-dose dexamethasone in patients who are double refractory to lenalidomide and bortezomib, according to Dr. Dimopoulos. Pomalidomide is a novel oral immunomodulatory drug.

Patients were randomized in a 2:1 ratio to receive 4 mg daily of pomalidomide for 3 weeks on followed by 1 week off plus weekly 40-mg doses of dexamethasone (n=302 patients) or high-dose dexamethasone for 4 days on followed by 4 days off (n=153 patients). They received treatment until the researchers found disease progression or toxicity to the medications.

Inclusion criteria included patients who were refractory to their last therapy, had taken ≥2 prior therapies, had failed treatment with lenalidomide and bortezomib, and had primary refractory disease or relapsed and refractory disease.

The last of the 455 patients enrolled on August 31, 2012, and the data cut-off was September 7, 2012, by which the occurrence of 242 events triggered the final progression-free survival analysis. There were also 106 events included for the interim overall survival analysis.

Median follow-up was 4 months, which Dr. Dimopoulos said was “very short.” Of the patients, 34% were randomized from June 30, 2012, to August 31, 2012. During the final progression-free survival analysis, the data monitoring committee recommended that patients in the high-dose dexamethasone group who had not progressed be allowed to receive the combination treatment due to its superiority, according to Dr. Dimopoulos. He said 29% of patients chose to switch groups.

The baseline characteristics of the patients were similar: median age was approximately 65 years, median number of prior therapies was 5, and median time from initial diagnosis to enrollment in the trial was 5.5 years. Of the patients in the high-dose dexamethasone group, 25% continued to receive treatment after the trial ended compared with 45% in the combination group.

The overall response rate was 21% in the combination group and 3% in the high-dose dexamethasone group (P<.001). Dr. Dimopoulos said the combination treatment led to a significant improvement in progression-free survival and overall survival regardless of the last prior treatment the patients received. It was also effective in patients with moderate renal impairment.

The most common grade 3 or 4 hematologic adverse event was neutropenia, found in 42% of patients in the combination group and 15% of patients who took high-dose dexamethasone. In addition, 7% of patients in the combination group and 6% of patients in the high-dose dexamethasone group discontinued the study due to an adverse event.