Efficacy and safety of less frequent dosing with elranatamab (ELRA) in patients with relapsed or refractory multiple myeloma (RRMM): A US subgroup analysis from MagnetisMM-3.

7549 Background: The ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of ELRA in patients (pts) with RRMM and no prior BCMA-directed therapy (Cohort A). With a median follow‐up of 33.9 mo, ORR was 61.0%, mPFS was 17.2 mo, and mOS was 24.6 mo. Here we report results for the subgroup of pts enrolled in MagnetisMM-3 in the US. Methods: Eligible pts had RRMM with disease refractory to ≥1 immunomodulatory drug, ≥1 proteasome inhibitor, and ≥1 anti-CD38 antibody. Pts were given subcutaneous ELRA as step-up priming doses followed by 76 mg QW for 6 cycles. Pts given QW dosing for ≥6 cycles who achieved partial response or better lasting ≥2 mo were transitioned to Q2W dosing and to Q4W after ≥6 cycles of Q2W dosing. The subgroup of pts within Cohort A enrolled in the US (n=47) was analyzed. As of the data cutoff date (September 10, 2024), the median follow‐up was 33.8 mo (95% CI, 32.9-35.7; estimated by reverse Kaplan–Meier), approximately 32 mo after the last pt first dose. Results: Pts in the US subgroup received a median of 5 prior lines of therapy (range, 2-22); 93.6% were triple-class refractory, and 46.8% were penta-drug refractory. Eight (17.0%) pts were Black or African American. ORR (95% CI) by Blinded Independent Central Review was 66.0% (50.7-79.1); 42.6% of pts achieved complete response (CR + stringent CR). Median (range) time to response was 1.08 mo (0.95-7.36), and median time to CR or better was 4.76 mo (1.22-12.75). Median duration of response (95% CI) was not reached (NR) (24.0 mo-not estimable [NE]); the probability of maintaining response at 30 mo (95% CI) was 65.7% (43.3-81.0). Median (95% CI) PFS was 27.3 mo (4.3–NE). Median (95% CI) OS was NR (14.9–NE); the probability of survival at 30 mo (95% CI) was 55.8% (40.1-68.9). Any grade [G] and G3/4 treatment-emergent adverse events were reported in 100% and 78.7% pts, respectively. Infections (any G, G3/4, G5) were reported in 70.2%, 40.4%, and 0.0%, respectively; 51.1% received Ig replacement. Anti-viral, anti-pneumocystis jirovecii pneumonia, anti-bacterial, and anti-fungal prophylaxis were received by 80.9%, 21.3%, 14.9%, and 8.5% of pts, respectively. The rate of cytokine release syndrome (CRS) was 61.7% (G1, 34.0%; G2, 27.7%; G≥3, 0.0%). Immune effector cell-associated neurotoxicity syndrome was reported in 8.5% of pts (G1, 4.3%; G2, 4.3%; G≥3, 0.0%). 22 pts switched from QW to Q2W, and 8 pts further switched from Q2W to Q4W dosing. Conclusions: The pts with RRMM enrolled in MagnetisMM-3 Cohort A, including the US subgroup, were heavily pretreated. Consistent with overall Cohort A data, ELRA was associated with deep, durable responses in the US subgroup, with a mPFS of 27.3 mo. CRS was G1 and G2 only. Infections were consistent with what was observed in the overall study population; infection prophylaxis including Ig replacement are recommended. Clinical trial information: NCT04649359 .