MRD-negative conversion and progression-free outcomes are significantly improved with daratumumab-lenalidomide (D-R) maintenance therapy in patients with newly diagnosed multiple myeloma (MM), according to a post hoc analysis of the phase 3 AURIGA study. This analysis evaluated patients who were anti-CD38 monoclonal antibody–naïve and post-transplant minimal residual disease (MRD)-positive, with a median follow-up of 32.3 months.
Development Of Daratumumab-Lenalidomide Subgroup Analysis
The study examined subgroups defined by high-risk cytogenetic abnormalities (HRCAs) according to original, revised, and modified International Myeloma Society (IMS) 2024 criteria. Across all high-risk subgroups, MRD-negative conversion rates at 12 months of maintenance were consistently higher with D-R compared with lenalidomide (R) alone. For instance, in patients with high-risk disease per original criteria, 31.8% achieved MRD negativity versus 6.7% with R; per revised criteria, conversion was 43.8% versus 13.3%; and using the modified IMS 2024 criteria, 41.2% converted versus 0%. Patients with cytogenetically ultra-high–risk disease (≥2 revised HRCAs) achieved a 54.5% MRD-negative rate with D-R versus 0% with R. These trends were mirrored in overall MRD-negative conversion rates across subgroups.
Efficacy Across Age, Race, And Risk
D-R maintenance demonstrated a consistent trend towards improved progression-free survival (PFS) versus R in high-risk and ultra-high–risk cytogenetic subgroups (HR [95% CI]: original 0.60 [0.21–1.70]; revised 0.53 [0.21–1.31]; modified 2024 0.45 [0.13–1.53]; ultra-high-risk 0.61 [0.17–2.25]). Notably, outcomes were comparable irrespective of age or race, with no additional safety concerns observed among older (≥65 years) or Black patients. The data underscore the potential of D-R maintenance to provide meaningful benefit across diverse patient populations, independent of baseline risk status.
Clinical Implications
These findings support the use of daratumumab-lenalidomide as a maintenance therapy strategy to enhance MRD-negative conversion and reduce disease progression in patients with newly diagnosed MM. The robust efficacy across cytogenetic risk groups and consistent safety profile highlight its role in personalised post-transplant management.
Reference
Foster L et al. Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses. Blood Cancer Journal. 2025;15:154.
