Interferon-alpha treatment in multiple myeloma: Meta-analysis of 30 randomised trials among 3948 patients

Background: After two decades of interferon (IFN) treatment in myeloma pati ents and many randomised clinical trials, no definite proof of its benefits exists. This meta-analysis of all available relevant published data tests the differences between IFN and control arms in a large patient population and addresses the issue of cost-effectiveness. Patients and methods: Meta-analysis was performed on 17 trials among 2333 p atients who received IFN-chemotherapy induction treatment or chemotherapy a lone and on 13 trials among 1615 patients on IFN maintenance therapy or wit hout treatment. Response rates and parameters of published Kaplan-Meier rel apse-free and overall survival curves were analysed. Results: Patients in IFN arms showed significantly better results in all in vestigated parameters: IFN-chemotherapy induction treatment yielded 6.6% hi gher response rates (2P < 0.002) as well as 4.8-month and 3.1-month prolong ations of relapse-free (P < 0.01) and overall survival (P < 0.01), respecti vely. Interferon maintenance therapy lead to 4.4-month (P < 0.01) and 7.0-m onth (P < 0.01) prolongations of relapse-free and overall survival, respect ively. Meta-analysis of all IFN trials combined resulted in 4.6-month and 3 .7-month IFN-related gains in relapse-free and overall survival, respective ly. As early as 6 and 12 months after the start of IFN treatment, percentag es of cumulative relapse-free and overall survival were always significantl y higher in IFN trial arms. IFN drug expenses for a one-year survival gain, as determined from AUCs of best-fitted Gompertz functions of IFN and contr ol survival curves, were estimated to be US$42,482.28 for induction therapy and US$18,968.16 for maintenance treatment. Conclusions: Significantly superior outcomes were consistently found in IFN trial arms by meta-analysis of published data. These results are in accord ance with a concomittantly conducted meta-analysis on individual patient da ta but were much easier to accrue. Taking all our results into account, i.e ., the consistently significant, although limited, improvement of clinical outcomes and its acceptable cost-effectiveness, IFN treatment of patients w ith multiple myeloma seems worthwhile to be considered.