Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA

• Published in: Leukemia Vol. 36; no. 4; pp. 1066 - 1077
• Main Authors: Facon, Thierry, Cook, Gordon, Usmani, Saad Z., Hulin, Cyrille, Kumar, Shaji, Plesner, Torben, Touzeau, Cyrille, Bahlis, Nizar J., Basu, Supratik, Nahi, Hareth, Goldschmidt, Hartmut, Quach, Hang, Mohty, Mohamad, Venner, Christopher P., Weisel, Katja, Raje, Noopur, Hebraud, Benjamin, Belhadj-Merzoug, Karim, Benboubker, Lotfi, Decaux, Olivier, Manier, Salomon, Caillot, Denis, Ukropec, Jon, Pei, Huiling, Van Rampelbergh, Rian, Uhlar, Clarissa M., Kobos, Rachel, Zweegman, Sonja
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2022; Nature Publishing Group; Springer Nature
• Subjects: 692/699/1541/1990/804; 692/700/565/1436/2185; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Cancer Research; Critical Care Medicine; Dexamethasone; Dexamethasone - therapeutic use; Frailty; Frailty - diagnosis; Hematology; Humans; Immunotherapy; Intensive; Internal Medicine; Lenalidomide - therapeutic use; Life Sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Minimal residual disease; Monoclonal antibodies; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Neutropenia; Oncology; Patients; Retrospective Studies; Steroids; Subgroups; Targeted cancer therapy
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-021-01488-8

In the phase 3 MAIA study of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd). We present a subgroup analysis of MAIA by frailty status. Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. Of the randomized patients (D-Rd, n  = 368; Rd, n  = 369), 396 patients were non-frail (D-Rd, 196 [53.3%]; Rd, 200 [54.2%]) and 341 patients were frail (172 [46.7%]; 169 [45.8%]). After a 36.4-month median follow-up, non-frail patients had longer PFS than frail patients, but the PFS benefit of D-Rd versus Rd was maintained across subgroups: non-frail (median, not reached [NR] vs 41.7 months; hazard ratio [HR], 0.48; P  < 0.0001) and frail (NR vs 30.4 months; HR, 0.62; P  = 0.003). Improved rates of complete response or better and minimal residual disease (10 –5 ) negativity were observed for D-Rd across subgroups. The most common grade 3/4 treatment-emergent adverse event in non-frail and frail patients was neutropenia (non-frail, 45.4% [D-Rd] and 37.2% [Rd]; frail, 57.7% and 33.1%). These findings support the clinical benefit of D-Rd in transplant-ineligible NDMM patients enrolled in MAIA, regardless of frailty status.