RANDOMIZED TRIAL OF INTERFERON MAINTENANCE IN MULTIPLE-MYELOMA - A STUDY OF THE NATIONAL-CANCER-INSTITUTE OF CANADA CLINICAL-TRIALS GROUP

Purpose: To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myelo ma who have responded to induction therapy with melphalan and predniso ne. Patients and Methods: in a multicenter trial, patients with sympto matic clinical stage land stage II and III multiple myeloma were regis tered at diagnosis and those who responded to melphalan-prednisone (MP )were randomized either to receive interferon (2 mU/m(2)) subcutaneous ly three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was r eached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated us ing life-table methods, and were adjusted in the analysis for imbalanc es in baseline prognostic factors. Results: Four hundred two patients were registered and 176 responders were randomized (85 to interferon a nd 91 to control), At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for cont rol (P = .16), but when adjusted for chance imbalances in baseline pro gnostic factors (mainly performance status), the median survival durat ion was 44 months and 33 months for interferon and control, respective ly (P = .049). Progression-free survival from randomization to first r elapse also favored interferon (unadjusted P < .002; adjusted P < .003 ). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discont inue interferon treatment, Conclusion: Interferon maintenance therapy improves progression-free and overall survival of patients with multip le myeloma who respond to melphalan cmd prednisone. Toxicity is substa ntial and must be weighed by patients against the potential benefits i n response duration and survival. (C) 1995 by American Society of Clin ical Oncology.