Elranatamab in combination with daratumumab and lenalidomide (EDR) in patients with newly diagnosed multiple myeloma (NDMM) not eligible for transplant: Initial results from MagnetisMM-6 part 1.

Abstract

7504 Background: Elranatamab (ELRA), a BCMA-CD3 bispecific antibody, induced deep and durable responses with a manageable safety profile in patients (pts) with relapsed/refractory multiple myeloma (RRMM). MagnetisMM-6 (NCT05623020) is a phase 3, open-label, randomized study evaluating the efficacy and safety of ELRA in combination with lenalidomide (R) ± daratumumab (DARA) (EDR or ER) vs DARA + R + dexamethasone (DRd) in pts with transplant-ineligible (TI) NDMM. Part 1 of the study evaluates the optimal dose of EDR or ER in pts with RRMM or NDMM to determine the recommended phase 3 dose for part 2. Initial results from part 1 dose level G (DLG) are presented. Methods: In DLG, eligible pts had TI (age ≥65 or age <65 years with comorbidities impacting the possibility of transplant) NDMM, measurable disease, ECOG ≤2, and adequate liver, renal and bone marrow function. Pts received subcutaneous (SC) ELRA with a priming regimen followed by ELRA 76 mg SC every 4 weeks (Q4W) on cycle (C) 1 day (D) 1; DARA 1800 mg SC weekly (D1, D8, D15, D22 in C1-C2), every 2 weeks (D1, D15 in C3-C6), and Q4W (D1 in C7+); and oral R 25 mg daily on D1-D21 in 28-day cycles. Endpoints assessed in DLG include safety and preliminary efficacy. Results: A total of 37 pts were enrolled in DLG; 34 received EDR. The median age was 75.0 years (range, 67-83); 37.8% were male; 86.5% were White, 13.5% Asian. Four patients (10.8%) had R-ISS stage III disease, 9 (24.3%) had ≥50% baseline bone marrow plasma cells, 1 (2.7%) had ECOG=2, none had EMD, and 9 (24.3%) were frail according to the simplified IMWG frailty score. At data cutoff (Dec 23, 2024), the median follow-up was 4.6 months (range, 1.2-6.2); treatment was ongoing in 33 pts. TEAEs were reported in 97.3% (G3/4 94.6%) of pts, hematological TEAEs in 78.4% (G3/4 70.3%), and infections in 64.9% (G3/4 18.9%). The most frequent TEAEs (any grade ≥25% or G3/4 ≥10%) are shown in the Table. CRS occurred in 62.2%, all ≤G2; 1 case of G2 ICANS was reported. There was one G5 candida pneumonia. Overall, 36 out of 37 pts are responders with 2 pending confirmation as of DCO. The confirmed ORR (95% CI) by investigator was 91.9% (78.1-98.3), 81.1% with VGPR or better. In pts enrolled ≥4 months before the DCO (n=23), confirmed ORR was 95.7% (78.1-99.9), all with VGPR or better. Conclusions: In pts with TI NDMM, EDR demonstrated a manageable safety profile consistent with the known toxicities of components. High response rate and early responses were observed. Enrollment in dose level H evaluating the ER combination is ongoing. Updated safety and efficacy data with a longer follow-up will be presented. Clinical trial information: NCT05623020 . TEAEs, % Any grade G3/4 Neutropenia, incl. neutrophil count decreased 70.3 67.6 CRS 62.2 0 Pyrexia 35.1 0 Anemia, incl. hemoglobin decreased 32.4 16.2 Injection site reaction 29.7 0 Nausea 27.0 0 Thrombocytopenia, incl. platelet count decreased 13.5 10.8 Asthenia 16.2 10.8