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

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.