Elranatamab, a b-cell maturation antigen-cd3 bispecific antibody, for patients with relapsed/refractory multiple myeloma: extended follow up and biweekly administration from the magnetismm-3 study

Introduction/Objectives: To report the findings of extended follow-up and biweekly administration of elranatamab monotherapy in patients (pts) with relapsed/refractory multiple myeloma (RRMM) naïve to BCMA-directed therapies enrolled in Cohort A of MagnetisMM-3. Materials and methods: MagnetisMM-3 (NCT04649359) is an open-label, multicenter, registration phase 2 study evaluating the efficacy and safety of elranatamab monotherapy in pts with RRMM. Eligible pts were refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody. Pts received subcutaneous elranatamab in 28-d cycles with step-up doses of 12 mg on cycle 1 day 1 (C1D1) and 32 mg on C1D4 followed by 76 mg once-weekly beginning C1D8. Pts treated for 6 cycles and achieving partial response (PR) or better, lasting ≥2 mo, were switched to 76 mg once every two weeks (Q2W). Results: Overall, 123 pts received elranatamab. Median pt age was 68.0 y (range, 36-89); 63.4% of pts had an ECOG PS ≥1. The median number of prior lines of therapy was 5.0 (2-22), with 96.7% and 42.3% of pts having triple-class- and penta-drug refractory disease, respectively. At data cutoff (≍12 mo after last pt initial dose), the median follow up was 12.8 mo (0.2-22.7); 34.1% of pts remained on treatment. The most common reasons for treatment discontinuation were progressive disease (39.0%) and adverse events (AE; 13.8%). Objective response rate per blinded independent central review (BICR) was 61% (95% CI 51.8-69.6), with 39 (31.7%) pts with complete response (CR) or stringent CR (sCR); very good partial response (VGPR) and PR were achieved in 29 (23.6%) and 7 (5.7%) pts, respectively. MRD-negativity (threshold 10−−5) was achieved by 92.0% (n = 23/25) of evaluable pts. Median duration of response (mDOR) has not been reached (95% CI 12.9-NE), and DOR at 12 mo was 74.1% (95% CI 60.5-83.6). In pts with CR/sCR or VGPR, mDOR was not reached by 12 mo; in pts with PR, mDOR was 5.2 mo (95% CI 1.6-NE). There were 46 responders by BICR who switched to Q2W dosing ≥24 wk prior to the data cutoff; among these pts, 80.4% maintained/improved their response ≥24 wk after the switch. Median progression-free and overall survival have not been reached by 12 mo, and the respective rates (95% CI) at 12 mo were 57.1% (47.2-65.9) and 62.0% (52.8-70.0). Most common grade 3/4 treatment emergent AEs were hematologic; grade 3/4 nonhematologic events reported in ≥5% of pts were COVID-pneumonia (10.6%), hypokalemia (9.8%), pneumonia (7.3%), sepsis (6.5%), hypertension (6.5%), ALT increased (5.7 %), and SARS-COV-2 test positive (5.7%). Among pts who switched to Q2W dosing (n = 58), the incidence of grade 3/4 AEs decreased by >10% after the switch. Discussion: Elranatamab remains efficacious and well tolerated in pts with RRMM after >1 y of follow-up. Updated analysis with a median follow-up of ≍15 mo, the longest of all phase 2 BCMA-CD3 bispecific antibody studies, including the outcome of pts who switched to the Q2W dosing, will be presented. Conclusion: These results support continued elranatamab development for pts with MM.