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通过 CAR-T 细胞疗法增强复发/难治性多发性骨髓瘤的血小板功能。

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma.

机构信息

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.

Department of Hematology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, 200434, Shanghai, China.

出版信息

Clin Exp Med. 2024 Sep 4;24(1):210. doi: 10.1007/s10238-024-01477-y.

Abstract

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

摘要

嵌合抗原受体 T(CAR-T)细胞疗法对复发/难治性(R/R)多发性骨髓瘤(MM)患者血小板功能的影响尚未得到充分研究。我们的队列包括 50 名接受 CAR-T 细胞治疗的 MM 患者。在淋巴细胞耗竭前,外周血中由胶原/二磷酸腺苷(CADP)诱导的平均血小板闭合时间(PCT)显著延长(195.24±11.740 s),CAR-T 细胞治疗后明显缩短(128.02±5.60 s),有统计学显著改善(67.22,95%CI 46.91-87.53,P<0.001)。这种治疗后的 PCT 与健康对照组(10.64,95%CI 1.11-22.40,P>0.05)无显著差异。此外,与 CAR-T 细胞输注前相比,CAR-T 细胞输注后反应大于部分缓解(PR)的患者 PCT 明显升高(P<0.001)。PCT 延长也与缓解状态不佳有关。在细胞因子释放综合征(CRS)分级 0-2 的患者中,PCT 超过 240.5 s 的患者无进展生存期(PFS)较短,PCT>240.5 s 组的中位 PFS 时间为 10.2 个月,而 PCT≤240.5 s 组为 22.0 个月。多变量分析显示,CAR-T 细胞治疗后 R/R MM 患者 PCT 超过 240.5 s 是总生存期(OS)的独立预后因素。该研究表明,CAR-T 细胞疗法增强了 R/R MM 患者的血小板功能,PCT 可能成为 CAR-T 细胞疗法疗效的潜在预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b47/11374909/288715693dfa/10238_2024_1477_Fig1_HTML.jpg

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