A review of the clinical studies of alpha-interferon in the management of multiple myeloma

Abstract

The treatment of multiple myeloma is multidisciplinary and requires attention not only to the primary disease itself but to its secondary manifestations. Melphalan remains the single most effective oral chemotherapeutic drug used to treat multiple myeloma. A major problem with the oral administration of the drug is its variable bioavailability. The presence of an L-phenylalanine moiety in the structure of melphalan makes it likely that gastrointestinal absorption occurs through the normal amino acid transport mechanisms and that the presence of food influences the drug's uptake. Another factor that complicates the bioavailability of this agent is the fact that melphalan undergoes spontaneous hydrolysis at physiologic pH. One of the controversies in myeloma therapy is the continuing debate over the possible superiority of complex, multiagent chemotherapy regimens compared with single melphalan and prednisone or cyclophosphamide and prednisone. It does appear that response frequencies are considerably greater with combination chemotherapy than with standard oral melphalan and prednisone treatment. It is probable that both approaches--single-agent chemotherapy with melphalan and prednisone versus combination chemotherapy--can play a role in remission induction therapy. It may be appropriate to treat the patient with a low tumor burden with melphalan and prednisone and treat more aggressive myeloma patients with triple alkylator therapy or other combinations of chemotherapy agents. The most promising activity of interferon alfa-2b (rIFN alpha 2b) in induction of myeloma remission appears to occur when rIFN alpha 2b is combined with multiple alkylating agents. Analysis of clinical trials suggests that sequential use of rIFN alpha 2b with cytotoxic therapy may be more active than when IFN alpha 2b is given concomitantly with cytotoxic therapy. It may be most plausible to use rIFN alpha 2b in maintenance of remission of myeloma. In the laboratory, interferons have the capacity to modulate oncogene expression and to decrease both in vitro colony formation and the labeling index of myeloma cells. Further, it has been shown that interferon can reduce the capacity for self-renewal in myeloma-forming cells. The following concepts will be discussed: 1. There is promising evidence that rIFN alpha 2b may improve the frequency and quality of remission in multiple myeloma when administered in an alternating schedule. There is some evidence that rIFN alpha 2b, when combined with cytotoxic therapy and given concomitantly, may be less active.(ABSTRACT TRUNCATED AT 400 WORDS)