Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL.
Department of Public Health Sciences, University of Chicago Biological Sciences Division, Chicago, IL.
Blood Adv. 2024 Jul 23;8(14):3785-3797. doi: 10.1182/bloodadvances.2024012727.
The optimal means of assessing candidacy of older adults (≥65 years) for chimeric antigen receptor T-cell (CAR-T) therapy are unknown. We explored the role of a geriatric assessment (GA)-guided multidisciplinary clinic (GA-MDC) in selecting and optimizing older adults for CAR-T. Sixty-one patients were evaluated in a GA-MDC (median age, 73 years; range, 58-83). A nonbinding recommendation ("proceed" or "decline") regarding suitability for CAR-T was provided for each patient based on GA results. Fifty-three patients ultimately received CAR-T (proceed, n = 47; decline, n = 6). Among patients who received B-cell maturation antigen (BCMA)-directed (n = 11) and CD19-directed CAR-T (n = 42), the median overall survival (OS) was 14.2 months and 16.6 months, respectively. GA uncovered high rates of geriatric impairment among patients proceeding to CAR-T therapy, with fewer impairments in those recommended "proceed." Patients recommended "proceed" had shorter median length of stay (17 vs 31 days; P = .05) and lower rates of intensive care unit admission (6% vs 50%; P = .01) than those recommended "decline." In patients receiving CD19- and BCMA-directed CAR-T therapy, a "proceed" recommendation was associated with superior OS compared with "decline" (median, 16.6 vs 11.4 months [P = .02]; and median, 16.4 vs 4.2 months [P = .03], respectively). When controlling for Karnofsky performance status, C-reactive protein, and lactate dehydrogenase at time of lymphodepletion, the GA-MDC treatment recommendation remained prognostic for OS (hazard ratio, 3.26; P = .04). Patients optimized via the GA-MDC without serious vulnerabilities achieved promising outcomes, whereas patients with high vulnerability experienced high toxicity and poor outcomes after CAR-T therapy.
对于年龄较大的成年人(≥65 岁)是否适合接受嵌合抗原受体 T 细胞(CAR-T)治疗,目前尚不清楚最佳的评估方法。我们探讨了老年评估(GA)指导的多学科诊所(GA-MDC)在选择和优化老年患者接受 CAR-T 治疗方面的作用。61 名患者在 GA-MDC 中接受了评估(中位年龄 73 岁;范围 58-83 岁)。根据 GA 结果,为每位患者提供了关于是否适合接受 CAR-T 治疗的非约束性建议(“进行”或“拒绝”)。最终,53 名患者接受了 CAR-T 治疗(进行,n=47;拒绝,n=6)。在接受 B 细胞成熟抗原(BCMA)靶向(n=11)和 CD19 靶向 CAR-T(n=42)治疗的患者中,中位总生存期(OS)分别为 14.2 个月和 16.6 个月。GA 在接受 CAR-T 治疗的患者中发现了较高的老年损伤率,而推荐“进行”的患者损伤较少。推荐“进行”的患者的中位住院时间较短(17 天 vs 31 天;P=0.05),入住重症监护病房的比例较低(6% vs 50%;P=0.01),而推荐“拒绝”的患者则较高。在接受 CD19 和 BCMA 靶向 CAR-T 治疗的患者中,与“拒绝”相比,“进行”的推荐与更好的 OS 相关(中位 OS,16.6 个月 vs 11.4 个月[P=0.02];中位 OS,16.4 个月 vs 4.2 个月[P=0.03])。当控制淋巴细胞耗竭时的 Karnofsky 表现状态、C 反应蛋白和乳酸脱氢酶后,GA-MDC 治疗建议仍然与 OS 相关(危险比,3.26;P=0.04)。通过 GA-MDC 进行优化且没有严重脆弱性的患者获得了有希望的结果,而脆弱性较高的患者在接受 CAR-T 治疗后毒性反应较高且结局较差。