Earlier phase 3 study findings showed significantly improved progression-free survival (PFS) for lenalidomide maintenance versus placebo after stem-cell transplant (SCT), and many of the patients in the placebo group without progressive disease crossed over to the lenalidomide maintenance therapy arm. A significantly longer overall survival (OS) was reported with patients in the lenalidomide maintenance arm.
This study examines the effect of lenalidomide versus placebo on OS and PFS from randomization, adjusting for the potentially favorable effects of crossover in patients in the placebo arm. Patients were randomized to lenalidomide maintenance (n = 231) or placebo (n = 229; intent-to-treat population). In the placebo arm, 76 patients without progressive disease crossed over to the lenalidomide maintenance arm. The median time from randomization to crossover was 11.5 months. A landmark OS analysis from the date of unblinding was performed; the treatment effect between crossover and noncrossover patients receiving placebo was relatively similar (hazard ratio, 0.53; 95% confidence interval, 0.25-1.13). As a result, researchers applied a rank-preserving structural failure time model for crossover adjustment.
Following crossover adjustment, the median OS in the placebo arm decreased from 79.0 to 70.9 months, and the median PFS in the placebo arm decreased from 28.9 to 25.8 months. Furthermore, the relative treatment effect for OS and PFS increased for lenalidomide versus placebo when end points were adjusted for crossover.
These data confirm that the allowed crossover from placebo to lenalidomide prior to progressive disease upon unblinding potentially diluted the treatment effect of lenalidomide maintenance. After adjusting for the potential effects of crossover, the improvements of OS and PFS were maintained in patients in the lenalidomide maintenance arm versus the placebo arm after SCT.
McCarthy PL, et al. ASCO Abstract 8037.
