Interferons in the treatment of multiple myeloma

Recombinant DNA technology has made adequate quantities of human interferons available for both in vitro and in vivo testing. In the clonogenic assay, RPMI-8226 myeloma cells were tested with recombinant interferon alfa-2b (Intron A), melphalan, cyclophosphamide, and prednisone. Prednisone used as a single agent had the least cytotoxic effect. Concentrations of alfa-2b as low as 1 unit/mL (international antiviral activity) showed a reduction in colony number of less than 30% of the untreated controlled cultures. Melphalan and cyclophosphamide showed measurable cytotoxic activity, expressed in terms of 50% inhibition of colony growth, at doses of 0.15 microgram/mL and 0.4 microgram/mL, respectively. Additive antiproliferative effects were noted with combinations of alfa-2b plus cyclophosphamide and alfa-2b plus prednisone. However, the alfa-2b-melphalan combination had a synergistic effect on tumor-cell colony reduction. Even greater cytotoxic activity was seen with the three-drug combination of alfa-2b, melphalan, and prednisone. Clinical trials have shown that alfa-2b may be effective in patients with relapsing and refractory multiple myeloma. Of 38 patients evaluated, seven responded to treatment. Three of the seven responders have continued to respond for over 33 months, with monoclonal proteins approaching undetectable levels. A pilot study of the feasibility of combining alfa-2b with melphalan and prednisone in previously untreated patients with multiple myeloma has been completed. Although response was not the primary objective of this study, an overall response rate of 78% was achieved using criteria established by the Chronic Leukemia Task Force. Phase II trials conducted thus far have established tumor responsiveness to interferons in human myeloma. To clearly define the role of these agents in the treatment of myeloma, well-planned multicenter studies are needed.