Early M-protein Dynamics Predicts Progression-Free Survival in Patients With Relapsed/Refractory Multiple Myeloma

This study aimed to predict long-term progression-free survival (PFS) using early M-protein dynamic measurements in patients with relapsed/refractory multiple myeloma (MM). The PFS was modeled based on dynamic M-Protein data from two phase 3 studies, POLLUX and CASTOR, which included 569 and 498 patients with relapsed/refractory multiple myeloma, respectively. Both studies compared active controls (lenalidomide and dexamethasone, and bortezomib and dexamethasone, respectively) alone vs. in combination with daratumumab. Three M-protein dynamic features from the longitudinal M-protein data were evaluated up to different time cutoffs (1, 2, 3, and 6 months). The abilities of early M-protein dynamic measurements to predict the PFS were evaluated using Cox proportional hazards survival models.

Both univariate and multivariable analyses suggest that maximum reduction of M-protein (i.e., depth of response) was the most predictive of PFS. Despite the statistical significance, the baseline covariates provided very limited predictive value regarding the treatment effect of daratumumab. However, M-protein dynamic features obtained within the first two months reasonably predicted PFS and the associated treatment effect of daratumumab. Specifically, the areas under the time-varying receiver operating characteristic curves for the model with the first two months of M-protein dynamic data were approximately 0.8 and 0.85 for POLLUX and CASTOR, respectively. Early M-protein data within first two months can provide a prospective and reasonable prediction of future long-term clinical benefit for MM patients.