Safety and Efficacy of BCMA CAR-T Cell Therapy in Older Patients With Multiple Myeloma

Abstract

Risks of B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy for patients with multiple myeloma (MM) include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, and infections. The efficacy and safety of BCMA CAR-T therapy in the geriatric setting, including complications such as falls and delirium, which may be more prevalent in older patients, have not been fully analyzed. We wanted to analyze the efficacy and safety of BCMA CAR-T therapy among older patients (age ≥70 at infusion) versus younger patients with MM. We analyzed all patients with MM who received any autologous BCMA CAR-T therapy over a 5-year period at our institution. Key endpoints included CRS, ICANS incidence, days to absolute neutrophil count (ANC) recovery, incidence of hypogammaglobulinemia (IgG < 400 mg/dL), infections within 6 months, progression-free survival (PFS), and overall survival (OS). Of 83 analyzed patients (age range 33-77), 22 (27%) were aged ≥70 at infusion. The older cohort had lower creatinine clearances (median 67.3 versus 91.9 mL/min, P < .001) and a higher proportion of patients with performance status ≥1 (59% versus 30%, P = .02) but were otherwise similar. Rates of any-grade CRS, any-grade ICANS, and days to ANC recovery were similar between groups. Rates of baseline hypogammaglobulinemia were 36% in older patients and 30% in younger patients (P = .60), whereas post-infusion hypogammaglobulinemia occurred in 82% versus 72%, respectively (P = .57). Infections occurred in 36% (n = 8) of the older cohort versus 52% (n = 32) of the younger cohort (P = .22). There were no statistically significant differences between the older and younger cohorts in terms of documented falls (9% versus 15%, P = .72) or non-ICANS delirium (5% versus 7%, P = 1.0). Median PFS was 13.1 months in older patients (95% confidence interval [CI], 9.2-not reached [NR]) versus 12.5 months in younger patients (95% CI 11.3-22.5, P = .42. Median OS was not reached in the older cohort (95% CI, NR-NR) versus 31.4 months in the younger cohort (95% CI, 24.8-NR) with P = .04. However, age ≥70 was not a significant predictor of OS after adjusting for high-risk cytogenetics, triple-class refractoriness, extramedullary disease, and bone marrow plasma cell burden. Although limited by small sample size and unmeasured confounders, our retrospective analysis did not demonstrate significant increases in CAR-T toxicity among older patients. This included toxicities associated with geriatric populations such as falls and delirium. Our paradoxical finding of borderline better OS among patients aged ≥70, which was not significant in regression modeling, may have been due to selection bias in favor of disproportionately healthy CAR-T candidates in the geriatric population. Overall, BCMA CAR-T remains a safe and effective option for older patients with MM.

Keywords: CAR-T therapy; Elderly; Geriatric; Multiple myeloma.