Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses

• Published in: Blood Cancer Journal
• Main Authors: Laahn Foster, Larry D. Anderson, Alfred Chung, Chakra P. Chaulagain, Erin Pettijohn, Andrew J. Cowan, Caitlin Costello, Sarah Larson, Douglas W. Sborov, Kenneth H. Shain, Rebecca Silbermann, Peter Voorhees, Maria Krevvata, Huiling Pei, Sharmila Patel, Vipin Khare, Annelore Cortoos, Robin Carson, Thomas S. Lin, Ashraf Badros
• Format: Article
• Language: English
• Published: Nature Publishing Group 2025-10-01
• Online Access: https://doi.org/10.1038/s41408-025-01355-0

Abstract In the primary analysis (32.3-month median follow-up) of the randomized, phase 3 AURIGA study (NCT03901963), daratumumab-lenalidomide (D-R) maintenance significantly improved MRD-negative conversion rates and reduced the risk of disease progression or death by 47% versus R maintenance in anti-CD38 monoclonal antibody–naïve and post-transplant MRD-positive patients with newly diagnosed MM. Here, we present a post hoc analysis across relevant subgroups, including high-risk cytogenetic abnormalities (HRCAs) per original, revised, and modified International Myeloma Society (IMS) 2024 criteria. MRD-negative (10−5) conversion rates by 12 months of maintenance were higher for D-R versus R across cytogenetically high-risk subgroups per original (31.8% vs 6.7%), revised (43.8% vs 13.3%), and modified IMS 2024 (41.2% vs 0%) criteria and cytogenetically ultra-high–risk disease (≥2 revised HRCAs; 54.5% vs 0%). Similar trends in overall MRD-negative conversion rates were observed across subgroups. D-R demonstrated a trend towards improved PFS versus R (HR [95% CI]) in cytogenetically high-risk subgroups per original (0.60 [0.21–1.70]), revised (0.53 [0.21–1.31]), and modified IMS 2024 (0.45 [0.13–1.53]) criteria and cytogenetically ultra-high–risk disease (0.61 [0.17–2.25]). Similar outcomes were observed regardless of age or race, with no additional safety concerns among older (≥65 years) or Black patients. These data support the benefit of D-R maintenance regardless of age, race, and risk status.