Minimal Residual Disease–Based End Point for Accelerated Assessment of Clinical Trials in Multiple Myeloma: A Pooled Analysis of Individual Patient Data From Multiple Randomized Trials

PURPOSE Newly approved drugs and combinations treating multiple myeloma (MM) have resulted in substantial improvements in patients’ survival. To deliver rapid access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to evaluate the minimal residual disease–negative complete response (MRD-CR) as an intermediate end point for progression-free survival (PFS) and overall survival (OS) in newly diagnosed (ND) transplant-eligible (NDTE) patients, ND transplant-ineligible (NDTinE) patients, and patients with relapsed/refractory (RR) MM. PATIENTS AND METHODS Individual patient data from 20 randomized multicenter trials were collected. Eleven studies (4,773 patients) with sufficient data were analyzed to evaluate whether 9- or 12-month MRD-CR classified at a 10–5 threshold could be reasonably likely to predict the clinical benefit of new agents regarding PFS and OS. Global odds ratio (OR) was estimated using the bivariate Plackett Copula model. Su...