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抗 CD19 CAR-T 细胞治疗老年复发/难治性大 B 细胞淋巴瘤患者:一项多中心研究

英文原题:Anti-CD19 chimeric antigen receptor T-cell therapy in older patients with relapsed or refractory large B-cell lymphoma: A multicenter study.

查看英文原题

Anti-CD19 chimeric antigen receptor T-cell therapy in older patients with relapsed or refractory large B-cell lymphoma: A multicenter study.

PubMed 2024/06/04(内容时间) Am J Hematol Q1 · IF 9.4(JCR 2025)

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中文摘要

尽管CAR-T 细胞疗法可能治愈复发/难治性(RR)大 B 细胞淋巴瘤(LBCL),但由于临床数据有限,老年患者接受该疗法的比例仍偏低。

因此,我们在真实世界环境中研究 CAR-T 治疗老年 RR LBCL 患者的安全性和疗效。这项多中心回顾性观察研究纳入来自美国 7 家机构、年龄 65 岁及以上、接受抗 CD19 CAR-T 治疗的 RR LBCL 患者。共纳入 226 例患者,输注时年龄中位数为 71 岁(范围 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 PFS 估计值分别为 54% 和 44%。第 180 天非复发死亡率(NRM)为 10.9%,主要由感染所致,且不受年龄组影响。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%。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 体能状态评分为 2、乳酸脱氢酶升高、肿瘤负荷大、疾病分期晚、结外受累、需要桥接治疗及既往使用苯达莫司汀,均与 PFS 较短相关。这些发现支持老年患者使用 CAR-T,包括 80 岁及以上人群。CAR-T 治疗年龄不影响安全性、生存和 NRM 结局。老年患者不应仅因实际年龄而被排除在 CAR-T 治疗之外。

展开英文摘要原文

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.

论文信息

作者
Tun AM、Patel RD、St-Pierre F、Ouchveridze E、Niu A、Thordardottir T、Obasi J、Rosenthal A
第一作者单位
Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas, Kansas City, Kansas, USA.United States
通讯作者单位
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.United States
文献类型
多中心研究 · 观察性研究
期刊
American journal of hematology2024 Sep
原文标识
PubMed 38837403 · DOI 10.1002/ajh.27381