Interferons in the treatment of multiple myeloma.

Recently, recombinant DNA methods have been successfully applied to interferon production, making adequate quantities available for both in vitro and in vivo testing. Although interferons are in the class of biologic response modifiers, they do have some direct cytotoxic effects on human tumor cells that can be quantitated in vitro with the colony-forming assay. In the clonogenic assay, RPMI-8226 myeloma cells were tested with interferon alfa-2b (Intron A, Schering Corp., Kenilworth, NJ), melphalan, cyclophosphamide, and prednisone. With concentrations of interferon alfa-2b as low as 1 U/ml (international antiviral activity), colony number was reduced to less than 30% of the untreated control cultures. Both melphalan and cyclophosphamide showed measurable cytotoxic activity, with the ID50 of melphalan at 0.15 microgram/ml and that of cyclophosphamide at 0.4 microgram/ml. Prednisone had the least cytotoxic effect when tested with these myeloma cells as a single agent. Additive antiproliferative effects were noted with combinations of interferon alfa-2b plus cyclophosphamide and interferon alfa-2b plus prednisone. However, the interferon-melphalan combination showed synergistic effects on tumor colony cell reduction. Even greater cytotoxic activity was seen with the three-drug combination of interferon alfa-2b, melphalan, and prednisone. Clinical trials have shown that interferon alfa-2b may be effective in relapsing and refractory patients with multiple myeloma. Of 38 evaluable patients, a total of seven responded to treatment; one patient had a complete response, and six had a partial response. 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 interferon alfa-2b with melphalan and prednisone in previously untreated patients with multiple myeloma has been completed. It is concluded that interferon alfa-2b, in dosages not exceeding 2.0 X 10(6) IU/m2, can be safely given in combination with melphalan and prednisone, without compromising melphalan dosage. Although response was not the primary objective of the study, an overall response of 75% was achieved using the criteria established by the Chronic Leukemia-Myeloma Task Force.