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既往异基因造血干细胞移植对复发/难治性多发性骨髓瘤嵌合抗原受体(CAR)T 细胞治疗的影响

英文原题:Impact of Previous Allogeneic Hematopoietic Stem Cell Transplantation on Chimeric Antigen Receptor (CAR) T Cell Treatment for Relapsed/Refractory Multiple Myeloma.

PubMed 2024/05/04(内容时间) Clin Lymphoma Myeloma Leuk Q1 · IF 4.1(JCR 2025)

研究概要

我们的数据证实,对于既往接受过 allo-HSCT 的患者,ide-cel 治疗是可行的。

中文摘要

背景:靶向 BCMA 的嵌合抗原受体(CAR)T 细胞可有效治疗复发/难治性多发性骨髓瘤(RRMM),但既往异基因造血干细胞移植(allo-HSCT)对 CAR T 细胞制备用淋巴细胞采集及后续 CAR T 细胞治疗的影响尚不清楚。患者与方法:我们回顾性分析接受伊德卡布他仑赛(ide-cel)治疗的 RRMM 患者中,有无 allo-HSCT 史者的淋巴细胞采集组成、CAR T 细胞扩增及治疗结局。共分析 27 例患者(11/27 为女性),年龄中位数 63 岁(范围 39–75 岁)。5 例患者(19%)有 allo-HSCT 史,移植至 ide-cel 治疗的中位间隔为 5.5 年。结果:单采前,有无既往 allo-HSCT 患者的白细胞计数、绝对淋巴细胞计数、CD3+ 细胞和单核细胞水平无差异。采集的 CD3+ 细胞产量或淋巴细胞采集物的细胞组成也无差异。ide-cel 输注一年后,既往接受与未接受 allo-HSCT 患者的 PFS 和 OS 分别无显著差异:PFS 率分别为 60% 和 45%(P=0.58),OS 率分别为 66.7% 和 74%(P=0.84)。CAR T 细胞扩增峰值出现在输注后第 7 天左右,且不受既往 allo-HSCT 影响(P=0.71)。随访期间未发现 GVHD。结论:数据证实,既往接受 allo-HSCT 的患者可行 ide-cel 治疗。此外,allo-HSCT 未影响淋巴细胞采集物细胞组成、临床结局或 ide-cel 的体内扩增。

展开英文摘要原文

BACKGROUND: Anti-BCMA-directed chimeric antigen receptor (CAR) T cells are effective treatment for patients with refractory/relapsed multiple myeloma (RRMM). However, little is known about the impact of previous allogeneic hematopoietic stem cell transplantation (allo-HSCT) on lymphocyte collection for production of CAR T cells and subsequent treatment with CAR T cells. PATIENTS AND METHODS: We performed a retrospective analysis of cellular composition of lymphocyte collections, CAR T cell expansion and treatment outcomes of RRMM patients undergoing therapy with idecabtagene vicleucel (ide-cel) with and without history of allo-HSCT. 27 patients (11/27 female) with median age 63 (range 39-75) years were analyzed. Five patients (19%) had the history of allo-HSCT median of 5.5 years before ide-cel. RESULTS: Prior to apheresis, the white blood cell, absolute lymphocyte counts, CD3+ cells and monocytes did not differ in patients with and without prior allo-HSCT. We also noticed no differences in the collected CD3+ yields or cellular compositions of lymphocyte collections. One year after ide-cel infusion, the progression-free survival and overall survival of patients with and without previous allo-HSCT did not differ with 60% and 45% respectively (P = .58) and 66.7% and 74% respectively (P = .84). The highest expansion of CAR T was detected between day 7 after infusion and showed no difference regarding previous allo-HSCT (P = .71). No graft-versus-host disease during the follow-up was detected. CONCLUSION: Our data confirm that the treatment with ide-cel is feasible for patients with prior allo-HSCT. Furthermore, allo-HSCT did not influence cellular composition of lymphocyte collections, clinical outcome or in vivo expansion of ide-cel.

论文信息

作者
Kirchberg J、Fischer L、Born P、Brunner F、Morgner C、Fürst D、Heyn S、Bach E
第一作者单位
Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Leipzig Medical Center, Leipzig, Germany; Comprehensive Cancer Center Central Germany, Leipzig, Jena, Germany.Germany
通讯作者单位
Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Leipzig Medical Center, Leipzig, Germany; Comprehensive Cancer Center Central Germany, Leipzig, Jena, Germany. Electronic address: vladan.vucinic@medizin.uni-leipzig.de.Germany
期刊
Clinical lymphoma, myeloma & leukemia2024 Sep
原文标识
PubMed 38821728 · DOI 10.1016/j.clml.2024.05.006