P09 DARATUMUMAB PLUS LENALIDOMIDE AND DEXAMETHASONE (D-RD) VERSUS LENALIDOMIDE AND DEXAMETHASONE (RD) ALONE IN TRANSPLANT-INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): UPDATED ANALYSIS OF THE PHASE 3 MAIA STUDY

Introduction: Daratumumab is a human IgGκ monoclonal antibody that is approved as monotherapy and in combination with standard-of-care regimens for relapsed/refractory multiple myeloma and in combination with standard-of-care regimens for NDMM. In the primary analysis of the phase 3 MAIA study (median follow-up, 28.0 months), D-Rd significantly improved progression-free survival (PFS) and the minimal residual disease (MRD)–negativity rate (10–5 sensitivity) versus Rd alone in transplant-ineligible patients with NDMM. With longer follow-up (median follow-up, 56.2 months), D-Rd significantly improved overall survival (OS) versus Rd. Here, we present an analysis of MAIA after a median follow-up of 64.5 months. Patients and methods: Patients with NDMM ineligible for high-dose chemotherapy and autologous stem cell transplant were randomized 1:1 to Rd ± D. Randomization was stratified by International Staging System disease stage (I vs II vs III), region (North America vs other), and age (<75 vs ≥75 years). All patients received 28-day cycles of Rd (R: 25 mg PO on Days 121; d: 40 mg PO on Days 1, 8, 15, and 22). In the D-Rd arm, D (16 mg/kg IV) was given once weekly in Cycles 12, once every 2 weeks in Cycles 3-6, and once every 4 weeks thereafter. In both groups, patients were treated until disease progression or unacceptable toxicity. PFS was the primary endpoint; key secondary endpoints included MRDnegativity rate (10–5 sensitivity, clonoSEQ® version 2.0), overall response rate (ORR), OS, and safety. Results: A total of 737 patients were randomized (D-Rd, n=368; Rd, n=369). At a median follow-up of 64.5 months, PFS was improved with D-Rd versus Rd (median, 61.9 vs 34.4 months; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.45-0.67; P<0.0001). D-Rd reduced the risk of death by 34% versus Rd. Median OS was not reached with D-Rd versus 65.5 months with Rd (HR, 0.66; 95% CI, 0.53-0.83; P=0.0003), with estimated 60-month OS rates of 66.6% and 53.6%, respectively. ORR was higher for D-Rd versus Rd (92.9% vs 81.6%; P<0.0001), as were rates of MRD negativity (32.1% vs 11.1%; P<0.0001) and sustained MRD negativity lasting ≥12 months (18.8% vs 4.1%; P<0.0001). The most common (≥15% of patients in either arm) grade 3/4 treatment-emergent adverse events (TEAEs; D-Rd/Rd) were neutropenia (54.1%/37.0%), anemia (17.0%/21.6%), pneumonia (19.5%/10.7%), and lymphopenia (16.5%/11.2%); grade 3/4 infection rates were 42.6%/29.6%. Pneumonia was the most common serious TEAE in both groups (18.7%/10.7%). Rates of treatment discontinuation due to TEAEs were lower with D-Rd (14.6%) versus Rd (23.8%). Conclusions: In this analysis of MAIA after a median follow-up of >5 years, the addition of DARA to Rd continued to demonstrate PFS and OS benefits in transplant-ineligible patients with NDMM. D-Rd also achieved higher MRD-negativity and ≥12-month sustained MRD-negativity rates versus Rd alone. No new safety concerns were observed with longer follow-up. These results continue to support the frontline use of D-Rd in transplant-ineligible patients with NDMM. Additional OS results based on extended follow-up will be presented.

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