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

Abstract

Background: After two decades of interferon (IFN) treatment in myeloma patients 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 patients who received IFN-chemotherapy induction treatment or chemotherapy alone and on 13 trials among 1615 patients on IFN maintenance therapy or without treatment. Response rates and parameters of published Kaplan Meier relapse-free and overall survival curves were analysed.

Results: Patients in IFN arms showed significantly better results in all investigated parameters: IFN-chemotherapy induction treatment yielded 6.6% higher response rates (2P < 0.002) as well as 4.8-month and 3.1-month prolongations of relapse-free (P < 0.01) and overall survival (P < 0.01), respectively. Interferon maintenance therapy lead to 4.4-month (P < 0.01) and 7.0-month (P < 0.01) prolongations of relapse-free and overall survival, respectively. 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, respectively. As early as 6 and 12 months after the start of IFN treatment, percentages of cumulative relapse-free and overall survival were always significantly 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 control 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 accordance with a concomittantly conducted meta-analysis on individual patient data 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 with multiple myeloma seems worthwhile to be considered.