Interferon-alpha 2b added to melphalan-prednisone for initial and maintenance therapy in multiple myeloma - A randomized, controlled trial

Objective: To evaluate the addition of low-dose interferon-alpha 2b to standard melphalan-prednisone therapy in patients with multiple myeloma. Design: Randomized, multicenter, phase III study. Setting: 15 university hospitals and 92 county hospitals in Sweden, Norway, Denmark, Finland, and Iceland. Patients: 583 patients with symptomatic multiple myeloma. Intervention: All patients received melphalan-prednisone every 6 weeks. Melphalan-prednisone therapy was interrupted after at least 8 courses in responding patients who achieved a plateau phase, and it was reinstituted at time of relapse. Patients randomly assigned to receive melphalan-prednisone and interferon also received interferon, 5 MU three times weekly, from the start of treatment through response, plateau phase, and relapse, until definitive failure of melphalan-prednisone occurred. Measurements: Survival was the main outcome measure. Secondary measures were response rate, response and plateau phase duration, and toxicity. All analyses were done according to the principle of intention-to-treat. Results: 45% of patients receiving melphalan-prednisone and 44% of patients receiving melphalan-prednisone and interferon achieved at least a partial response. Response duration and plateau phase duration were longer for patients receiving melphalan-prednisone and interferon than for patients receiving melphalan-prednisone alone (P < 0.05); the difference in median duration was 5 to 6 months. Toxicity was higher with melphalan-prednisone and interferon, and this led to premature discontinuation of interferon therapy in one third of patients and to a reduced overall dose intensity for melphalan. The median survival time was 29 months for patients receiving melphalan-prednisone and 32 months for patients receiving melphalan-prednisone and interferon. The risk ratio for death for patients receiving melphalan-prednisone compared with patients receiving melphalan-prednisone and interferon was 1.02 (95% CI, 0.89 to 1.40). Conclusions: Adding continuous low-dose interferon to standard melphalan-prednisone therapy does not improve response rate or survival. However, response duration and plateau phase duration are prolonged by maintenance therapy with interferon.