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Shaji K. Kumar, MD
Shaji K. Kumar, MD
Posted: Thursday, December 4, 2025
Based on the primary analysis of the multicenter phase III AURIGA trial, the addition of daratumumab to standard-of-care maintenance therapy with lenalidomide significantly improved measurable residual disease (MRD)-negative conversion rates and reduced the risk of disease progression or death by 47% in anti-CD38 monoclonal antibody–naive and posttransplant MRD-positive patients with newly diagnosed multiple myeloma. The results of post hoc subgroup analyses, which were published in Blood Cancer Journal by Laahn Foster, MD, of the University of Virginia, Charlottesville, and colleagues, appear to support its benefit regardless of age, race, and risk status.
In brief, patients were randomly assigned to receive up to 36 cycles of maintenance lenalidomide with (n = 99) or without (n = 101) subcutaneous daratumumab. The present analysis, conducted in the intention-to-treat population, examined subgroups with high unmet medical need, including older and Black patients and those with cytogenetically high-risk disease as defined by established and recent criteria.
After 12 months of maintenance therapy, the MRD-negative (defined as < 10-5) conversion rates were higher with vs without daratumumab across cytogenetically high-risk subgroups, whether defined by the original (31.8% vs 6.7%), revised (43.8% vs 13.3%), or modified (41.2% vs 0%) International Myeloma Society (IMS) 2024 criteria, as well as in cytogenetically ultra–high-risk disease (≥ 2 revised high-risk cytogenetic abnormalities; 54.5% vs 0%). The investigators observed similar trends in overall MRD-negative conversion rates across subgroups.
Lenalidomide with vs without daratumumab demonstrated a trend toward improved progression-free survival in cytogenetically high-risk subgroups per original (hazard ratio [HR] = 0.60), revised (HR = 0.53), and modified (HR = 0.45) IMS 2024 criteria, as well as in patients with cytogenetically ultra–high-risk disease (HR = 0.61). Similar outcomes were seen regardless of age or race, with no additional safety concerns identified among older (≥ 65 years) or Black patients.
“Additional studies with larger sample sizes are needed to confirm these findings,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit nature.com.
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