CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
大 B 细胞淋巴瘤 CAR-T 细胞治疗后的非复发死亡：来自 DESCAR-T 注册登记的 LYSA 研究
英文原题：Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry.
查看英文原题
Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry.
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中文摘要
靶向 CD19 的嵌合抗原受体（CAR）T 细胞可诱导持久缓解，并有望治愈相当比例的复发/难治性大 B 细胞淋巴瘤患者。
然而，部分患者接受 CAR-T 后可能死于与淋巴瘤无关的原因。目前对 CAR-T 治疗后的非复发死亡率（NRM）了解有限。
本研究使用法国 DESCAR-T 登记数据库，分析 NRM 的发生率和死因，并识别 NRM 危险因素。研究报告了 2018 年 7 月至 2022 年 4 月期间，在法国 27 个中心接受标准治疗 axicabtagene ciloleucel（n = 598）或 tisagenlecleucel（n = 359）的 957 例患者。中位随访 12.4 个月期间，48 例患者发生总体 NRM（占所有患者 5.0%）：其中 9 例为早期 NRM（输注后第 28 天前；占所有患者 0.9%，占总体 NRM 的 19%），39 例为晚期 NRM（输注后第 28 天及以后；占所有患者 4.1%，占总体 NRM 的 81%）。总体 NRM 死因分布为：感染 56%（非 COVID-19 感染 29%，COVID-19 感染 27%）、细胞因子释放综合征 10%、卒中 6%、脑出血 6%、第二原发恶性肿瘤 6%、免疫效应细胞相关神经毒性 4%，其他死因 10%。研究还报告了早期 NRM 和总体 NRM 的危险因素。多变量分析显示，糖尿病及淋巴细胞清除时铁蛋白升高均与总体 NRM 风险增加相关。研究结果可能有助于医生选择和管理患者，以降低 CAR-T 治疗后的 NRM。
展开英文摘要原文
CD19 chimeric antigen receptor (CAR) T cells can induce prolonged remissions and potentially cure a significant proportion of patients with relapsed/refractory large B-cell lymphomas.
However, some patients may die of causes unrelated to lymphoma after CAR T-cell therapy. To date, little is known about the nonrelapse mortality (NRM) after CAR T-cell therapy. Using the French DESCAR-T registry, we analyzed the incidence and causes of NRM and identified risk factors of NRM.
We report on 957 patients who received standard-of-care axicabtagene ciloleucel (n = 598) or tisagenlecleucel (n = 359) between July 2018 and April 2022, in 27 French centers. With a median follow-up of 12. 4 months, overall NRM occurred in 48 patients (5. 0% of all patients): early (before day 28 after infusion) in 9 patients (0. 9% of all patients and 19% of overall NRM), and late (on/after day 28 after infusion) in 39 patients (4.
1% of all patients and 81% of overall NRM). Causes of overall NRM were distributed as follows: 56% infections (29% with non-COVID-19 and 27% with COVID-19), 10% cytokine release syndromes, 6% stroke, 6% cerebral hemorrhage, 6% second malignancies, 4% immune effector cell associated neurotoxicities, and 10% deaths from other causes.
We report risk factors of early NRM and overall NRM. In multivariate analysis, both diabetes and elevated ferritin level at lymphodepletion were associated with an increased risk of overall NRM.
Our results may help physicians in patient selection and management in order to reduce the NRM after CAR T-cell therapy.
论文信息
- 作者
- Lemoine J、Bachy E、Cartron G、Beauvais D、Gastinne T、Di Blasi R、Rubio MT、Guidez S
- 单位
- Department of Hematology, CHU de Rennes, Rennes, France.France
- 文献类型
- 非美国政府资助研究
- 期刊
- Blood advances2023 Nov 14
- 原文标识
- PubMed 37672383 · DOI 10.1182/bloodadvances.2023010624
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