Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma

purpose: In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m(2) subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma, A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST), Materials and Methods: Three clinical health stares were defined in this analysis: time with toxicity (TOX), rime without disease relapse or toxicity (TWiST), and time following disease relapse (REL), Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time. Results: The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001), Conclusion: The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities. J Clin Oncol 16:2834-2839. (C) 1998 by American Society of Clinical Oncology.