Outcomes in Frail Patients Receiving BCMA-directed Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma

• Bispecific antibodies are safe and effective in frail and elderly patients with multiple myeloma

• Advanced age, worse performance status, and higher comorbidity burden do not predict inferior outcomes with bispecific antibodies in myeloma

In addition to advanced age, patients with relapsed refractory multiple myeloma (RRMM) are often frail with pre-existing comorbidities and poor performance status and have been excluded from clinical trials evaluating bispecific antibodies (BsAb). To evaluate clinical characteristics and outcomes based on frailty, we conducted a single center retrospective study of patients with RRMM who received BCMA-directed BsAb. Frailty was defined using the simplified frailty index based on age, ECOG PS, and Charlson comorbidity index (CCI); non-frail = score 0-1, frail = score ≥2. Of 102 patients analyzed (age range 40 - 88), 40 (39%) were considered frail. The frail group had more patients with age ≥ 70 years (73% vs 29%, p <0.001), ECOG PS ≥ 2 (36% vs 0%, p <0.001), and worse median CCI (2 vs 1, p <0.001). Patients in the frail group experienced similar rates of all grade CRS (58% vs 60%, p= 0.99), ICANS (15% vs 8%, p= 0.44), and TRM (13% vs 21%, p= 0.27) compared to the non-frail group. Best overall response rate (ORR) was 80% (15% sCR/CR, 48% VGPR) in the frail group vs 73% (23% sCR/CR, 31% VGPR) in the non-frail group (p= 0.40). With a median follow-up of 8.6 months (range 3-14), there was no significant difference in median PFS (Not reached vs 11 months, p= 0.051) or OS (37 vs 25 months, p= 0.37) between the frail and non-frail groups, respectively. Hence, BsAb were deemed safe and effective for elderly and frail patients with RRMM.