(OA-07) 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

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. Five pts (13.5%) had R-ISS stage III disease, 9 (24.3%) had ≥50% baseline bone marrow plasma cells, 1 (2.7%) had an ECOG performance status of 2, none had extramedullary disease, and 9 (24.3%) were frail according to the simplified IMWG frailty score. At data cutoff (Apr 1, 2025), the median follow-up was 7.9 months (range, 1.2-9.5); treatment was ongoing in 32 pts.

Treatment-emergent adverse events (TEAEs) were reported in 100% (grade [G]3/4 94.6%) of pts, hematological TEAEs in 83.8% (G3/4 78.4%), and infections in 70.3% (G3/4 18.9%). Frequent (any grade ≥10%) infections were upper respiratory tract infection (21.6%, G3/4 0%) and Escherichia urinary tract infection (10.8%, G3/4 2.7%). There was one G5 Candida pneumonia. CRS occurred in 62.2%, all ≤G2; 1 case of G2 ICANS was reported. Anti-viral, anti-Pneumocystis jirovecii, anti-bacterial, and anti-fungal prophylaxis were received by 81.1%, 83.8%, 10.8%, and 16.2% of pts, respectively; 91.9% received Ig replacement.

The confirmed ORR (95% CI) by investigator was 97.3% (85.8-99.9); 94.6% with VGPR or better. The median (range) time to response was 1.5 (0.3-4.2) months and to VGPR or better was 2.4 (1.2-4.3) months.

Conclusions:

In pts with TI NDMM, EDR demonstrated a manageable safety profile consistent with the known toxicities of components. High response rates and early responses were observed, with responses expected to deepen with longer follow-up. Enrollment in dose level H evaluating the ER combination is ongoing.