Journal Article

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study

Raje, Noopur, Weisel, Katja, Pei, Huiling, Moreau, Philippe, Plesner, Torben, Venner, Christopher P., Goldschmidt, Hartmut, Borgsten, Fredrik, Bahlis, Nizar, Wang, George, Macro, Margaret, Krevvata, Maria, Kumar, Shaji K., Nahi, Hareth, O’Dwyer, Michael, Orlowski, Robert Z., Perrot, Aurore, Frenzel, Laurent, Leleu, Xavier, Hulin, Cyrille, Basu, Supratik, Usmani, Saad Z., Facon, Thierry, Carson, Robin, Quach, Hang, Tiab, Mourad

2025

Overview

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.5 months), transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint was PFS; secondary endpoints included overall response rate (ORR) and measurable residual disease (MRD)-negativity rate (10 ). PFS favored D-Rd versus Rd in most subgroups, including patients aged ≥75 years (HR, 0.59; 95% CI, 0.44-0.79), frail patients (HR, 0.64; 95% CI, 0.48-0.85), patients with high-risk cytogenetics (HR, 0.59; 95% CI, 0.44-0.80), and patients with isolated gain(1q21) (HR, 0.36; 95% CI, 0.19-0.67). ORRs, MRD-negativity rates, and sustained (≥12 months) MRD-negativity rates were higher with D-Rd versus Rd across subgroups. In patients aged ≥75 years, rates of grade 3/4 and serious treatment-emergent adverse events (TEAEs) were similar for D-Rd and Rd, but discontinuation due to TEAEs was lower for D-Rd. Results support use of D-Rd for high-risk patients, supporting D-Rd as a standard of care for transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as NCT02252172.

• Publisher: Nature Publishing Group
• Subject: Adult / Aged / Aged, 80 and over / Antibodies, Monoclonal - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Cytogenetics / Dexamethasone / Dexamethasone - administration & dosage / Female / Follow-Up Studies / Humans / Immunotherapy / Lenalidomide - administration & dosage / Male / Middle Aged / Monoclonal antibodies / Multiple myeloma / Multiple Myeloma - drug therapy / Multiple Myeloma - mortality / Multiple Myeloma - pathology / Prognosis / Risk groups / Subgroups / Survival / Survival Rate / Targeted cancer therapy