Maintenance therapy with thalidomide (Thalomid) and prednisone after autologous stem cell transplantation in patients with multiple myeloma improved progression-free survival but not overall survival, according to results of a phase III trial reported in Blood. Patients receiving maintenance therapy were more likely to experience adverse events and report worsening health-related quality of life “with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems,” the investigators reported.
The randomized, controlled trial compared thalidomide/prednisone as maintenance therapy with observation in 332 patients. Eligible patients were required to have received melphalan at 200 mg/m2 followed by autologous stem cell transplantation. “The study precluded the use of bortezomib (Velcade) or lenalidomide (Revlimid) before [autologous stem cell transplantation] to isolate the impact of maintenance with thalidomide,” the researchers noted. The trial was conducted and analyzed by the National Cancer Institute of Canada Clinical Trials Group, and patients were accrued from centers in Canada and, in collaboration with the Eastern Cooperative Oncology Group, the United States.
At a median follow-up of 4.1 years, overall survival was 68% among patients receiving thalidomide/prednisone and 60% in the observation group (HR = 0.77; P = .18). The maintenance therapy was, however, “associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; HR = 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P = .0004). Median survival after first disease recurrence was 27.7 months with thalidomide/prednisone and 34.1 months in the observation group,” the investigators reported.
“Twelve thromboembolic events were observed in patients receiving thalidomide/prednisone and there were no events in the observation arm (12 of 165 or 7.3% vs 0; P = .0004),” the researchers wrote. Nonhematologic events that occurred more frequently in the patients receiving thalidomide/prednisone included hyperglycemia, edema, hypertension, and fatigue.
“Our findings of inferior [health-related quality of life] outcomes in patients receiving thalidomide/prednisone call into question the benefits of a strategy to provide this agent as maintenance therapy for all patients and invite evaluations of predictive biomarkers that might better direct this treatment,” the authors concluded. “Future trials should also be conducted to determine whether other agents, such as lenalidomide or bortezomib, may demonstrate survival and/or [health-related quality of life] benefits as maintenance therapy after [autologous stem cell transplantation]. Finally, our results juxtaposing [progression-free survival, health-related quality of life, and overall survival] support ongoing debates about which outcomes should drive treatment policies, especially when sequencing of newly available therapies is possible.” ■
Stewart AK, et al: Blood 121:1517-1523, 2013.