Interferon alpha in the therapy of multiple myeloma

Response rates of 20% were achieved when interferon alpha (IFN) was applied as single agent treatment for multiple myeloma. A synergistic activity was observed when IFN was combined with chemotherapeutic agents in vitro and in vivo. These observations led to a series of randomized trials comparing chemotherapy alone with the combination of IFN and chemotherapy which yielded controversial results. Ludwig et al have analyzed presently available data of randomized trials in a systematic overview. In 16 trials, 2286 patients were randomized either for induction therapy with chemotherapy or IFN combined with chemotherapy. The IFN dose ranged between 4.8 and 18.7 MU/week. The overall response rate was 45.9% for patients treated with chemotherapy alone compared to 54.4% for patients treated with IFN alpha and chemotherapy. The gain of relapse-free survival was 6 months and the gain of overall survival was 5 months for IFN-treated patients. Advances in treatment were due to the expense of more severe side-effects in IFN-treated patients expressed by hematological side-effects, fever, nausea and neurological as well as psychological alterations. IFN maintenance therapy was evaluated from eight trials comprising 929 patients randomized for IFN-treatment or 'wait and see'. IFN maintenance treatment prolonged the average relapse-free survival by 7 months and prolonged the average overall survival by 5 months. Younger patients, patients in good performance status and patients with lower tumor burden seem to benefit most from the addition of IFN to chemotherapy or from IFN maintenance therapy. In conclusion, IFN shows a minor beneficial effect on response rates, progression-free and overall survival in the above mentioned patient group and might be applied when high-dose chemotherapy with transplantation is not feasible. IFN has been shown to be effective for maintenance therapy in patients with lower tumor burden who have responded to induction therapy.