Background: Multiple myeloma is predominantly a disease of elderly and frail pts, who are often ineligible for intensive therapies. Data from the ongoing Phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of elranatamab in pts with RRMM and no prior BCMA-directed therapy (Cohort A). Here we report results for subgroups of pts by age and frailty. Methods: Eligibility criteria, dosing and administration were previously reported (Bahlis, ASH 2022). Subgroups of pts within Cohort A (n = 123) were analyzed by age: < 65 (n = 43) vs ≥65 years n = 80), and frailty: non-frail (n = 84) vs frail (n = 39). A simplified frailty scale was used (Facon et al, Leukemia 2020). Results include data up through ~12 months after last pt initial dose. Results: The median treatment duration was 8.2 vs 5.5 mo in the < 65 vs ≥65 years, and 6.4 vs 5.6 mo in the non-frail and frail subgroups, respectively. Discontinuation occurred in 62.8% vs 67.5% of pts aged < 65 vs ≥65 years and in 63.1% vs 71.8% of the non-frail vs frail groups, respectively. The most common reason for discontinuation in all subgroups was progressive disease, 51.2%, 32.5%, 42.9%, and 30.8% of < 65, ≥65 years, non-frail, and frail subgroups, respectively. The objective response rate (ORR) (95% CI) was 58.1% (42.1%, 73.0%) vs 62.5% (51.0%, 73.1%) for pts aged < 65 vs ≥65 years. Median duration of response was not reached in either age subgroup. The probability of maintaining response (95% CI) at 12 mo was 74.1% (51.0%, 87.5%) vs 73.8% (55.7%, 85.4%) for pts aged < 65 vs ≥65 years. The ORR (95% CI) for non-frail pts was 63.1% (51.9%, 73.4%) vs 56.4% (39.6%, 72.2%) for frail pts. Median duration of response was not reached in either frailty subgroup. The probability of maintaining response at 12 mo (95% CI) was 76.0% (60.2%, 86.2%) vs 70.5% (41.9%, 86.9%) for non-frail vs frail pts. Any Grade treatment-emergent adverse events (TEAEs) were reported in 100% of pts in the study. Grade 3/4 TEAEs were reported in 74.4%, 68.8%, 73.8% and 64.1% of pts in < 65, ≥65, non-frail and frail subgroups, respectively. Infections (Any Grade; Grade 3/4; Grade 5) were reported in 72.1%, 32.6% and 4.7% vs 68.8%, 40.0% and 6.3% in < 65 and ≥65 pts, respectively, and in 70.2%, 38.1% and 4.8% vs 69.2%, 35.9% and 7.7% in non-frail and frail pts, respectively. The rate of cytokine release syndrome was similar in patients with respect to age ( < 65, 58.1%; ≥65 years, 57.5%) and frailty groups (non-frail, 57.1%; frail, 59.0%). Immune effector cell-associated neurotoxicity syndrome was reported in 2.3%, 6.3%, 6.0% and 2.6% of pts in < 65, ≥65, non-frail and frail subgroups, respectively. Conclusions: Elranatamab is efficacious and has a manageable safety profile in elderly or frail pts with RRMM and may be a treatment option for those ineligible for more intensive myeloma therapies. Clinical trial information: NCT04649359.