Number needed to treat (NNT) as a measure of drug benefit: Lenalidomide versus bortezomib for treatment of relapsed/refractory multiple myeloma (MM).

Abstract

e18562 Background: Lenalidomide(LEN) and bortezomib(BORT) are active agents in the treatment of refractory MM. The former is administered 25 mg/day orally on days 1-21 of repeated 28-day cycles. The latter as a 1.3 mg/m^2 intravenous dose on days 1, 4, 8 and 11 for eight, three week cycles. Both agents have demonstrated an improvement in disease response, progression free (PFS) and overall survival (OS) in the refractory MM setting. NNT represents the number of patients that need to be treated with a new intervention in order to have one additional patient deriving benefit, and is a powerful approach that can be used to make sense of numerical results from clinical trials. In this analysis, the NNT approach was used to compare LEN and BORT in patients with relapsed MM. Methods: The pivotal randomized trials for LEN (Weber, Dimopoulos, 2007) and BORT (Richardson, 2005) were reviewed. A key requirement for a NNT comparative analysis is that all outcomes be measured against a comparable control. The NNT was then calculated for both agents with respect to disease response and PFS at 12 months by taking the reciprocal of the absolute differences in treatment effect between the experimental therapies and the control group. Results: For a disease response, the NNT for LEN and BORT was 3 and 5 patients respectively; to have one additional patient achieving a disease response. A difference in the NNT was also noted for PFS at 12 months; only 3 patients would need to be treated with LEN for an additional patient remaining progression free compared to 9 with BORT. This is a relevant finding because it suggests a 3 fold relative increase in clinical benefit in patients treat with LEN compared to BORT. Conclusions: In situations of multiple numerical outcomes from randomized trials, NNT approach is a simple and effective method to express the findings in a clinically meaningful way. In this analysis, it appears that more patients treated with LEN are likely to respond and to achieve a 12 month PFS than comparable patients treated with BORT. Possible reasons for this effect include differences in the trial population, extent of disease, and/or true differences in efficacy.