DaraKPd (anti-CD38 mAb + proteasome inhibitor + IMiD) delivers 38.3-mo mPFS in CD38-naïve RRMM

Daratumumab (anti-CD38 monoclonal antibody) combined with carfilzomib (proteasome inhibitor), pomalidomide (IMiD), and dexamethasone (DaraKPd) was evaluated in a phase 2 MMRC study in relapsed/refractory multiple myeloma with 1–3 prior lines, prior PI+IMiD required, and prior CD38 mAb excluded (n=28; 82% lenalidomide-refractory; 86% prior ASCT; 64% high-risk cytogenetics; NCT01665794). The primary endpoint was met with an nCR rate of 39% after 4 cycles (95% CI 22–59%), and with 70.2 months median follow-up the mPFS was 38.3 months (95% CI 18.4–NR) and mOS was NR; 36-month PFS/OS were 54%/75%. Depth appeared biologically meaningful: 65% achieved MRD-negativity at 10^-5 (42% sustained ≥1 year), and MRD-negative patients had longer mPFS (69.4 vs 14.0 months; p=0.002); no new safety signals or treatment-related deaths were reported—though cross-trial, the mPFS here is far beyond common “backbone” options like D-Pd in APOLLO (mPFS 12.4 months overall) or PVd in OPTIMISMM at early relapse (20.7 months in a first-relapse subanalysis), acknowledging these are not head-to-head comparisons.