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BCMA-CAR T 细胞治疗后自体造血干细胞移植巩固治疗对复发或难治性多发性骨髓瘤患者生存的影响。

Effects of Consolidation Therapy With Autologous Hematopoietic Stem Cell Transplantation After BCMA-CAR T-Cell Therapy on the Survival of Patients With Relapsed or Refractory Multiple Myeloma.

机构信息

Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Transplant Cell Ther. 2024 Nov;30(11):1080.e1-1080.e11. doi: 10.1016/j.jtct.2024.08.024. Epub 2024 Sep 3.

Abstract

Despite the success of chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory multiple myeloma (RRMM), failure after CAR T-cell therapy remains an unmet medical need. An effective consolidation therapy after CAR T-cell therapy may improve the prognosis of RRMM. To investigate the effects of consolidation therapy with autologous hematopoietic stem cell transplantation (AHCT) after B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy on the prognosis of RRMM patients. This retrospective study included 39 RRMM patients who received BCMA-targeted CAR T-cell therapy. Basic clinical, therapy, and outcome data were collected, and factors associated with survival were analyzed. Among the 39 RRMM patients included in the study, 15 had high-risk cytogenetics and 11 had extramedullary disease (EMD). All 39 patients reached peak CAR T-cell expansion within 28 days after infusion. Twenty-six patients developed cytokine release syndrome, including 12 grade 1 and 14 grade 2 cases. Survival analysis revealed that high-risk cytogenetics, high tumor load (International Staging System [ISS] stage III), and EMD were negatively associated with progression-free survival (PFS) and overall survival (OS). Thirteen patients received consolidation AHCT therapy 50-276 days after CAR T-cell therapy, with a median interval of 92 days. No serious complications occurred after consolidation AHCT. Survival analysis showed that consolidation AHCT effectively improved OS and PFS over maintenance chemotherapy. Moreover, Cox regression analysis identified low tumor load (ISS stage I/II) and consolidation AHCT as independent predictors of superior PFS and OS and high-risk cytogenetics as an independent risk factor for poor PFS. Consolidation AHCT after CAR T-cell therapy in RRMM patients can improve patient survival.

摘要

尽管嵌合抗原受体(CAR)T 细胞疗法在复发或难治性多发性骨髓瘤(RRMM)中取得了成功,但 CAR T 细胞治疗后的失败仍然是一个未满足的医疗需求。CAR T 细胞治疗后进行有效的巩固治疗可能会改善 RRMM 的预后。本研究旨在探讨 BCMA 靶向 CAR T 细胞治疗后自体造血干细胞移植(AHCT)巩固治疗对 RRMM 患者预后的影响。本回顾性研究纳入了 39 例接受 BCMA 靶向 CAR T 细胞治疗的 RRMM 患者。收集了基本的临床、治疗和结局数据,并分析了与生存相关的因素。在纳入研究的 39 例 RRMM 患者中,15 例存在高危细胞遗传学异常,11 例存在骨髓外疾病(EMD)。所有 39 例患者在输注后 28 天内达到 CAR T 细胞扩增高峰。26 例患者发生细胞因子释放综合征,包括 12 例 1 级和 14 例 2 级。生存分析显示,高危细胞遗传学、高肿瘤负荷(国际分期系统[ISS]III 期)和 EMD 与无进展生存期(PFS)和总生存期(OS)呈负相关。13 例患者在 CAR T 细胞治疗后 50-276 天接受巩固 AHCT 治疗,中位间隔时间为 92 天。巩固 AHCT 后无严重并发症发生。生存分析显示,与维持化疗相比,巩固 AHCT 可有效改善 OS 和 PFS。此外,Cox 回归分析确定低肿瘤负荷(ISS 分期 I/II)和巩固 AHCT 是 PFS 和 OS 良好的独立预测因素,高危细胞遗传学是 PFS 不良的独立危险因素。RRMM 患者 CAR T 细胞治疗后行巩固 AHCT 可改善患者生存。

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