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

Abstract

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.

• Authors: Thierry Facon, Gordon Cook, Saad Z Usmani, Cyrille Hulin, Shaji Kumar, Torben Plesner, Cyrille Touzeau, Nizar J Bahlis, Supratik Basu, Hareth Nahi, Hartmut Goldschmidt, Hang Quach, Mohamad Mohty, Christopher P Venner, Katja Weisel, Noopur Raje, Benjamin Hebraud, Karim Belhadj-Merzoug, Lotfi Benboubker, Olivier Decaux, Salomon Manier, Denis Caillot, Jon Ukropec, Huiling Pei, Rian Van Rampelbergh, Clarissa M Uhlar, Rachel Kobos, Sonja Zweegman
• Journal: Leukemia (Leukemia) Vol. 36 Issue 4 Pg. 1066-1077 (04 2022) ISSN: 1476-5551 [Electronic] England
• PMID: 34974527 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Antibodies, Monoclonal
• daratumumab
• Dexamethasone
• Lenalidomide

Topics

• Antibodies, Monoclonal
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Dexamethasone (therapeutic use)
• Frailty (diagnosis)
• Humans
• Lenalidomide (therapeutic use)
• Multiple Myeloma (diagnosis, drug therapy)
• Retrospective Studies