Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas, Kansas City, Kansas, USA.
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Am J Hematol. 2024 Sep;99(9):1712-1720. doi: 10.1002/ajh.27381. Epub 2024 Jun 4.
Chimeric antigen receptor T-cell (CAR-T) therapy, despite being a potentially curative therapy in relapsed or refractory (RR) large B-cell lymphoma (LBCL), remains underutilized in older patients due to limited clinical data. We therefore studied the safety and efficacy of CAR-T therapy in older patients with RR LBCL in the real-world setting. Patients aged ≥65 years with RR LBCL, treated with anti-CD19 CAR-T therapy at 7 US institutions were included in this multicenter, retrospective, observational study. In total, 226 patients were included. Median age at infusion was 71 years (range 65-89). Best objective and complete response rates were 86% and 62%, respectively. Median follow-up after infusion was 18.3 months. The median progression-free survival (PFS) was 6.9 months, with 6- and 12-month PFS estimates of 54% and 44%, respectively. The nonrelapse mortality (NRM) rate was 10.9% at day 180, primarily due to infections, and not impacted by the age groups. Grade ≥3 cytokine release syndrome and neurotoxicity occurred in 7% and 26%, respectively. In univariate analysis, no significant difference in PFS was seen regardless of the age groups or CAR-T type, whereas ECOG PS ≥2, elevated LDH, bulky disease, advanced stage, extranodal involvement, the need for bridging therapy, and prior bendamustine exposure were associated with shorter PFS. These findings support the use of CAR-T in older patients, including those aged ≥80 years. The age at CAR-T therapy did not influence safety, survival, and NRM outcomes. Older patients should not be excluded from receiving CAR-T therapy solely based on their chronological age.
嵌合抗原受体 T 细胞（CAR-T）疗法在复发或难治性（RR）大 B 细胞淋巴瘤（LBCL）患者中具有潜在的治愈作用，但由于临床数据有限，在老年患者中的应用仍受到限制。因此，我们在真实环境中研究了 CAR-T 疗法在老年 RR LBCL 患者中的安全性和疗效。这项多中心、回顾性、观察性研究纳入了 7 家美国机构接受抗 CD19 CAR-T 治疗的年龄≥65 岁 RR LBCL 患者。共纳入 226 例患者。输注时的中位年龄为 71 岁（范围为 65-89 岁）。最佳客观缓解率和完全缓解率分别为 86%和 62%。输注后中位随访时间为 18.3 个月。中位无进展生存期（PFS）为 6.9 个月，6 个月和 12 个月的 PFS 估计值分别为 54%和 44%。非复发死亡率（NRM）在 180 天为 10.9%，主要是由于感染，与年龄组无关。≥3 级细胞因子释放综合征和神经毒性的发生率分别为 7%和 26%。在单变量分析中，无论年龄组或 CAR-T 类型如何，PFS 均无显著差异，而 ECOG PS≥2、LDH 升高、肿块疾病、晚期、结外受累、需要桥接治疗以及先前使用苯达莫司汀与较短的 PFS 相关。这些发现支持在老年患者中使用 CAR-T，包括年龄≥80 岁的患者。CAR-T 治疗时的年龄并不影响安全性、生存和 NRM 结局。不应该仅仅因为患者的年龄而将他们排除在接受 CAR-T 治疗之外。
