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RRMM 患者 CAR-T 细胞治疗后细胞免疫的长期分析

英文原题:Long-term analysis of cellular immunity in patients with RRMM treated with CAR-T cell therapy.

查看英文原题

Long-term analysis of cellular immunity in patients with RRMM treated with CAR-T cell therapy.

PubMed 2023/10/31(内容时间) Clin Exp Med Q2 · IF 4.5(JCR 2025)

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中文摘要

CAR-T 细胞疗法对复发/难治性多发性骨髓瘤(RRMM)疗效显著,但CAR-T 输注后免疫缺陷尚未得到充分研究。本研究评估了CAR-T 输注后获得缓解的126例患者的细胞免疫。淋巴细胞清除(LD)化疗后第0天,绝对淋巴细胞计数(ALC)及各淋巴细胞亚群绝对计数均较基线显著降低。输注后30天内,99%的患者发生3级淋巴细胞减少,其中多数至第180天已恢复。随访期间,CD4+ T细胞计数中位数始终低于基线及正常值下限(LLN);相比之下,CD8+ T细胞计数中位数至第30天恢复至基线和LLN水平。B细胞计数中位数在第60天仍低于基线,并于第180天恢复至基线和LLN水平。输注后前30天,27例(21.4%)患者发生29次感染,多数为轻至中度(21/29,72.4%)。第30天后,44例(34.9%)患者发生56次感染,其中20次为重度感染。一名患者于CAR-T 输注后3.8个月死于菌血症。

总之,多数RRMM患者出现由LD化疗和CAR-T 输注导致的细胞免疫缺陷。CAR-T 输注30天后,ALC及大多数淋巴细胞亚群逐渐恢复,但CD4+ T细胞除外。部分患者存在持续时间较长的CD4+ T细胞免疫抑制,但未发生严重感染。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cell therapy exhibits remarkable efficacy against refractory or relapsed multiple myeloma (RRMM); however, the immune deficiency following CAR-Ts infusion has not been well studied. In this study, 126 patients who achieved remission post-CAR-Ts infusion were evaluated for cellular immunity. Following lymphodepletion (LD) chemotherapy, the absolute lymphocyte count (ALC) and absolute counts of lymphocyte subsets were significantly lower than baseline at D0. Grade 3 lymphopenia occurred in 99% of patients within the first 30 days, with most being resolved by 180 days.

The median CD4 + T-cell count was consistently below baseline and the lower limit of normal (LLN) levels at follow-up. Conversely, the median CD8 + T-cell count returned to the baseline and LLN levels by D30. The median B-cell count remained lower than baseline level at D60 and returned to baseline and LLN levels at D180.

In the first 30 days, 27 (21. 4%) patients had 29 infections, with the majority being mild to moderate in severity (21/29; 72. 4%). After day 30, 44 (34. 9%) patients had 56 infections, including 20 severe infections. One patient died from bacteremia at 3. 8 months post-CAR-Ts infusion.

In conclusion, most patients with RRMM experienced cellular immune deficiency caused by LD chemotherapy and CAR-Ts infusion. The ALC and most lymphocyte subsets gradually recovered after day 30 of CAR-Ts infusion, except for CD4 + T cells. Some patients experience prolonged CD4 + T-cell immunosuppression without severe infection.

论文信息

作者
Cheng H、Ji S、Wang J、Hua T、Chen Z、Liu J、Shao L、Wang X
第一作者单位
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China.China
通讯作者单位
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. zimu05067@163.com.China
期刊
Clinical and experimental medicine2023 Dec
原文标识
PubMed 37907623 · DOI 10.1007/s10238-023-01232-9