Strategies for combining interferon with chemotherapy for the treatment of multiple myeloma

Interferon has been evaluated in many settings for the treatment of multiple myeloma. As a single agent in refractory disease, interferon in partially purified preparations and, more recently, recombinant alpha-interferon (rIFN) has demonstrated response rates of 10% to 20%. Because of its demonstrated activity as a single agent, various combinations of rIFN with chemotherapy have been evaluated. The Italian Myeloma Study Group has found that maintenance therapy with rIFN alpha 2b prolongs the time to relapse following a year of standard chemotherapy. The Cancer and Acute Leukemia Group B has evaluated a regimen that combines rIFN alpha 2b with simultaneous melphalan and prednisone. In a third approach, the Eastern Cooperative Oncology Group has developed a regimen consisting of alternating cycles of VBMCP (vincristine, carmustine, melphalan, cyclophosphamide, and prednisone) chemotherapy with rIFN alpha 2b. This regimen yields an 80% objective response rate, including 30% complete responses defined by disappearance of M-protein from serum and urine and complete morphologic normalization of the bone marrow. On preliminary analysis, the response duration and median survival were both approximately 1 year longer than generally observed in patients with multiple myeloma on standard regimens. Hematologic toxicity, although more severe than that observed previously with VBMCP alone, was not associated with increased infections or bleeding. To substantiate the observation of apparent increased activity of VBMCP + rIFN alpha 2b, the Eastern Cooperative Oncology Group is currently conducting a randomized comparison of this regimen with treatment using VBMCP alone.