The phase 3 AURIGA trial (NCT03901963) has revealed that the addition of daratumumab (Darzalex) to lenalidomide maintenance therapy significantly improves outcomes in patients with newly diagnosed multiple myeloma (NDMM) who have undergone transplant and are minimal residual disease (MRD)-positive. The study, a randomized trial conducted in the US and Canada, compared daratumumab plus lenalidomide to lenalidomide alone in patients who had achieved at least a very good partial response (VGPR) post-transplant.
Primary Endpoint Achieved
The primary endpoint of the trial, MRD-negative conversion rate at 12 months, was significantly higher in the daratumumab/lenalidomide arm, reaching 50.5% compared to just 10.8% in the lenalidomide-only arm (P < 0.0001). This statistically significant difference underscores the potential of daratumumab to deepen responses and improve disease control in this patient population.
Improved Responses and Progression-Free Survival
Beyond the primary endpoint, the study also demonstrated that patients receiving daratumumab/lenalidomide achieved deeper complete responses (CR) at a rate of 75.8%, compared to 61% in the lenalidomide arm. Furthermore, progression-free survival (PFS) at 30 months was notably higher in the daratumumab/lenalidomide arm at 83%, versus 66% for lenalidomide alone. This translates to a 47% reduction in the risk of progression or death with the addition of daratumumab.
Safety and Tolerability
While adverse events (AEs) were more frequent in the daratumumab/lenalidomide arm, the safety profile was generally consistent with the known profiles of the individual agents. Serious AEs occurred in 30% of patients in the daratumumab/lenalidomide arm compared to 22% in the lenalidomide arm. The most common AE was neutropenia, observed in approximately 54% of the daratumumab/lenalidomide arm and 47% of the lenalidomide arm. Notably, the trial was conducted during the COVID-19 pandemic, and a higher incidence of COVID-19 infections was observed in the daratumumab/lenalidomide arm.
According to Ashraf Z. Badros, MB, ChB, professor of medicine, director of the Multiple Myeloma Service, and vice chair of the Clinical Research Committee for the Program in Oncology at the University of Maryland School of Medicine in Baltimore, surprisingly, there was no significant high-grade toxicity noted in the trial, and most patients did well. The discontinuation rate due to AEs was higher in the daratumumab/lenalidomide arm (14%) compared to the lenalidomide arm (8%). However, patients remained on the daratumumab/lenalidomide arm for a longer median duration (30 months vs 20 months), suggesting that the increased drug exposure may account for the higher reporting of AEs. Aside from cytopenia and infection, no new safety signals were identified.
Implications for Clinical Practice
The AURIGA trial provides compelling evidence for the benefit of adding daratumumab to lenalidomide maintenance in MRD-positive NDMM patients post-transplant. These findings may influence treatment strategies, potentially leading to improved long-term outcomes for this patient population. Future research may focus on using MRD status to guide the duration of treatment, with considerations for stopping treatment after 2-3 years in some patients, particularly those with standard-risk disease.
