A review of the clinical studies in which interferons have been involved has shown that they may have a role in the treatment of multiple myeloma. Twelve studies, each of which involved at least 10 evaluable cases (352 in total) with various dose schedules involving leukocyte, lymphoblastoid and recombinant alpha-IFNs, reported 8 4 3 % objective responses. The response duration was rather short but, in a few cases, it lasted for more than a year. In addition t o a decrease in the levels of M-protein and/or urine Bence-Jones protein, a decrease in the number of plasma cells in the bone marrow, disappearance of bone pain, healing of bone lesions, increase of hemoglobin and/or restoration of normal immunoglobulins were observed. Higher doses of recombinant alpha-interferons seemed t o exert a stronger effect. No clear difference in response rate was observed between myeloma which had been previously treated and that which was not treated. A t least clinically, therefore, there seems t o be no cross-resistance between alpha-interferons and conventional anti-tumor drugs. A randomized study comparing low-dose leukocyte interferon with intermittent high-dose melphalan-prednisone has given a lower response rate for interferon. Beta-and gamma-interferons have not yet been extensively studied. They have been used at low doses producing an objective response in 7% of 68 and 2% of 45 evaluable cases, respectively. Since the myelosuppression of interferons is transient and, after discontinuation of interferon therapy, peripheral blood cells usually recover within a week, it may be possible t o use interferon in combination with agents that have strong myelosuppressive effects provided there is no synergism.
Despite considerable progress in the treatment of multiple myeloma over the last 2 decades, its prognosis is still quite poor. Very few drugs produce therapeutic benefit in patients with this disease which has become refractory to therapy with melphalan and prednisone or similar combinations, and has a fatal outcome within a few years (Woodruff et al., 1981). Although a combination of vincristine, adriamycin and dexamethasone (VAD) was recently reported to give a high response rate in these patients (Barlogie et al., 1984), new drugs active in this disease are still eagerly awaited.
Early clinical studies with natural leukocyte interferons (IFNs) demonstrated anti-tumor activity against multiple myeloma. These early studies were restricted, however, because the species-specific nature of IFNs meant that they were only available in limited quantities and were costly to produce. Developments in cell engineering and recombinant DNA technology, however, now enable larger quantities of highly purified IFNs to be produced. Recent studies with lymphoblastoid, fibroblastoid and recombinant IFNs produced in this manner have confirmed their antitumor activity against multiple myeloma. The response rates, however, have not been high and the exact role of IFNs in the treatment of multiple myeloma is still debatable.
In this report, the results of clinical studies on multiple myeloma using various types of IFN will be reviewed with special reference to the results of a phase II study with recombinant human alpha-IFN (IFN alfa-2a). The potential of IFNs in the treatment of multiple myeloma will also be discussed. et al. (1979) reported a transient response in a patient with multiple myeloma refractory to melphalan and given 3-6 X lo6 IU i.m. daily of IFN prepared from human leukocyte cultures (leukocyte alpha-IFN) at the Central Public Health Laboratory, Helsinki. Mellstedt et al. (1979) reported one complete response (CR) and 2 partial responses (PR) (classified according to standard criteria) from 4 patients treated with 3-6 X lo6 IU i.m. daily of leukocyte alpha-IFN prepared by the Finnish Red Cross Blood Transfusion Service.
TREATMENT OF MULTIPLE MYELOMA WITH HUMAN LEUKOCYTE INTERFERON
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Although Osserman et al. (1980) reported only 3 minor responses (MR) from 11 patients in the American Cancer Society phase I1 trial using 3-6 x lo6 IU of the leukocyte alpha-IFN prepared by the Finnish Red Cross, Gutterman et al. (1980) reported one CR, 2 PR and 3 improvements in 10 patients treated with 3-9 X lo6 IU i.m. daily (Table I). The remission lasted from 24 months to more than 64 months on a maintenance dose of 3 X lo6 IU t.i.w.