Efficacy and Safety of Elranatamab by Age and Frailty in Patients With Relapsed/Refractory Multiple Myeloma (RRMM): Subgroup Analysis From MagnetisMM-3

Introduction/Objectives: Multiple myeloma is a disease of elderly and frail people, who are often predominantly ineligible for intensive therapies. The objective of this analysis is to report the efficacy and safety of elranatamab monotherapy by age and frailty in B-cell maturation antigen-naïve patients (pts) with relapsed or refractory multiple myeloma (RRMM) enrolled into cohort A of the ongoing phase 2 MagnetisMM -3 (NCT04649359) study. Materials and methods: Eligibility criteria, dosing and administration were previously reported (Bahlis et al, 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. Discussion: Elranatamab is efficacious and has a manageable safety profile in elderly or frail pts with RRMM. Conclusions: Elranatamab may be a treatment option for those ineligible for more intensive myeloma therapies.