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Safety and efficacy of BCMA CAR-T cell therapy in older patients with multiple myeloma

Transplant Cell Ther. 2023 Mar 16:S2666-6367(23)01171-5. doi: 10.1016/j.jtct.2023.03.012. Online ahead of print.


BACKGROUND: 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.

OBJECTIVES: To analyze the efficacy and safety of BCMA CAR-T therapy among older patients (age ≥70 at infusion) versus younger patients with MM.

STUDY DESIGN: 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).

RESULTS: 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 vs 91.9 mL/min, p<0.001) and a higher proportion of patients with performance status ≥1 (59% vs 30%, p=0.02) 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=0.60), while post-infusion hypogammaglobulinemia occurred in 82% vs 72% respectively (p=0.57). Infections occurred in 36% (n=8) of the older cohort versus 52% (n=32) of the younger cohort (p=0.22). There were no statistically significant differences between the older and younger cohorts in terms of documented falls (9% vs 15%, p=0.72) or non-ICANS delirium (5% vs 7%, p=1.0). Median PFS was 13.1 months in older patients (95% CI 9.2-not reached [NR]) vs 12.5 months in younger patients (95% CI 11.3-22.5, p=0.42. Median OS was not reached in the older cohort (95% CI: NR-NR) vs 31.4 months in the younger cohort (95% CI 24.8-NR) with p=0.04. 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.

CONCLUSIONS: While 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.

PMID:36933659 | DOI:10.1016/j.jtct.2023.03.012

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