Daratumumab (CD38 mAb) boosts depth of response across age/frailty in TIE NDMM (MAIA/CEPHEUS)

Daratumumab is an anti-CD38 monoclonal antibody added to immunomodulatory backbone Rd (MAIA; DRd vs Rd; n=368 vs 369) or to proteasome-inhibitor triplet VRd (CEPHEUS; DVRd vs VRd; n=144 vs 145) in transplant-ineligible newly diagnosed multiple myeloma, with subgrouping by age (<70, 70–<75, ≥75y) and IFM simplified frailty (0–1 non-frail; ≥2 frail) at median follow-up 64.5mo (MAIA) and 76.0mo (CEPHEUS). Across all age strata, PFS favored dara-based therapy (MAIA HR 0.35 <70y; 0.64 age 70–<75; 0.59 ≥75; CEPHEUS HR 0.60 <70; 0.60 age 70–<75; 0.46 ≥75) with deeper responses: ≥CR improved vs control (e.g., MAIA <70y 56.4% vs 31.2%; ≥75y 44.4% vs 28.6; CEPHEUS <70y 85.7% vs 68.6%; ≥75y 80.5% vs 44.4) alongside higher MRD negativity at 10^-5 with ≥CR and higher sustained MRD negativity (≥12±1mo apart) (e.g., frail MAIA sustained MRD neg 15.7% vs 4.1; frail CEPHEUS 39.6% vs 17.1). Safety was reported as consistent with known profiles and generally comparable across arms/subgroups, but the abstract does not provide grade ≥3 AE rates, discontinuations, or infection/cytopenia detail—important given older/frail enrichment (in MAIA, 46% frail; in CEPHEUS TIE, 29% frail).