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

Clin Transl Sci. 2020 Nov;13(6):1345-1354. doi: 10.1111/cts.12836. Epub 2020 Jul 17.

Abstract

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 III studies, POLLUX and CASTOR, which included 569 and 498 patients with relapsed/refractory MM, 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 2 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 2 months of M-protein dynamic data were ~ 0.8 and 0.85 for POLLUX and CASTOR, respectively. Early M-protein data within the first 2 months can provide a prospective and reasonable prediction of future long-term clinical benefit for patients with MM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Biomarkers, Tumor / blood*
  • Clinical Trials, Phase III as Topic
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Multiple Myeloma / blood
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / mortality*
  • Myeloma Proteins / analysis*
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / mortality*
  • Progression-Free Survival
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Reference Values
  • Risk Assessment / methods

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Myeloma Proteins
  • daratumumab