BCMA 靶向 CAR T 细胞治疗后造血恢复延迟时使用 CD34+ 干细胞增强的疗效和安全性。

Efficacy and Safety of CD34+ Stem Cell Boost for Delayed Hematopoietic Recovery After BCMA Directed CAR T-cell Therapy.

机构信息

Department of Pharmacy, Medical University of South Carolina, Hollings Cancer Center, Charleston, South Carolina.

Divison of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

出版信息

Transplant Cell Ther. 2023 Sep;29(9):567-571. doi: 10.1016/j.jtct.2023.05.012. Epub 2023 May 22.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment outcomes for patients with relapsed refractory multiple myeloma (RRMM). Despite supportive care with growth factors and thrombopoietin (TPO) mimetics, nearly half of the patients experience severe and prolonged cytopenias after CAR T infusion, which have become a major therapeutic challenge for patients with RRMM. Given the successful use of CD34+ autologous hematopoietic stem cells for treatment of non- or delayed engraftment after allogeneic and autologous stem cell transplantations, there is a need to explore the role of previously stored autologous stem cells as a boost for post-CAR T cytopenias in RRMM. We performed a multicenter retrospective analysis of adult patients with RRMM who received previously collected and stored CD34+ stem cell boosts after CAR T-cell therapy between 2 July 2020 and 18 January 2023. Indications for boost were determined per physician discretion and primarily included cytopenias and related complications. Overall, a total of 19 patients received stem cell boost, at a median dose of 2.75 × 10 CD34+ cells/kg (range 1.76-7.38), given at a median of 53 days (range 24-126) after CAR T infusion. Eighteen (95%) patients successfully recovered hematopoiesis after stem cell boost with median time for neutrophil, platelet, and hemoglobin engraftment of 14 (range 9-39), 17 (range 12-39), and 23 (range 6-34) days after the boost, respectively. Stem cell boosts were well tolerated, with no patients experiencing infusion reactions. Although infections were common and severe before stem cell boost, only 1 patient experienced a new infection after boost. All patients had experienced independence from use of growth factors, TPO agonists, and transfusions at the last follow-up. Autologous stem cell boosts can be effectively and safely used to promote hematopoietic recovery for post-CAR T cytopenias in patients with RRMM. Stem cell boosts can be a very effective rescue measure for post-CAR T cytopenias and related complications, as well as supportive care needs.

摘要

嵌合抗原受体 (CAR) T 细胞疗法彻底改变了复发/难治性多发性骨髓瘤 (RRMM) 患者的治疗效果。尽管接受了生长因子和血小板生成素 (TPO) 模拟物的支持性治疗,但近一半的患者在接受 CAR T 输注后会出现严重且持久的细胞减少症,这已成为 RRMM 患者的主要治疗挑战。鉴于 CD34+ 自体造血干细胞在治疗异基因和自体干细胞移植后非植入或延迟植入方面的成功应用,有必要探索先前储存的自体干细胞作为 RRMM 患者 CAR T 后细胞减少症的助推器的作用。我们对 2020 年 7 月 2 日至 2023 年 1 月 18 日期间接受过先前采集和储存的 CD34+干细胞助推器的 RRMM 成年患者进行了多中心回顾性分析。根据医生的判断确定了助推器的适应症,主要包括细胞减少症和相关并发症。总体而言,共有 19 名患者接受了干细胞助推器治疗,中位剂量为 2.75×10 CD34+细胞/kg(范围 1.76-7.38),在 CAR T 输注后中位时间 53 天(范围 24-126)给予。18 名(95%)患者在接受干细胞助推器治疗后成功恢复造血,中性粒细胞、血小板和血红蛋白植入的中位时间分别为 14(范围 9-39)、17(范围 12-39)和 23(范围 6-34)天。干细胞助推器治疗耐受性良好,无患者发生输注反应。尽管在接受干细胞助推器治疗之前感染很常见且严重,但只有 1 名患者在接受助推器治疗后出现新感染。所有患者在最后一次随访时均无需使用生长因子、TPO 激动剂和输血。自体干细胞助推器可有效且安全地用于促进 RRMM 患者 CAR T 后细胞减少症的造血恢复。干细胞助推器是治疗 CAR T 后细胞减少症及相关并发症以及支持性护理需求的非常有效的抢救措施。

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