8039 Background: MagnetisMM-3 (NCT04649359) is an open-label, multicenter, registrational phase 2 study evaluating the efficacy and safety of elranatamab monotherapy in pts with RRMM; pts naïve to BCMA-directed therapies were enrolled in Cohort A. Methods: Eligible pts were refractory to at least 1 PI, 1 IMiD, and 1 anti-CD38 antibody. Pts received SC elranatamab in 28-d cycles with step-up doses of 12 mg on C1D1 and 32 mg on C1D4 followed by 76 mg QW beginning C1D8. Pts treated for 6 cycles and achieving partial response (PR) or better with response persisting ≥2 mo were switched to 76 mg Q2W, 46 and 58 pts are included in the Q2W efficacy and safety analyses, respectively. 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 and median prior lines of therapy was 5.0 (2−22); 96.7% and 42.3% of pts were triple-class- and penta-drug refractory, 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. Most common reasons for permanent 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 cut-off; 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 non-hematologic 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, the incidence of Grade 3/4 AEs decreased by > 10% after the switch. Conclusions: 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. These results support continued elranatamab development for pts with MM. Clinical trial information: NCT04649359 .