阿基仑赛注射液治疗复发或难治性大 B 细胞淋巴瘤的安全性。

Safety of Axicabtagene Ciloleucel for the Treatment of Relapsed or Refractory Large B-Cell Lymphoma.

机构信息

The University of Texas MD Anderson Cancer Center, Houston, TX.

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH.

出版信息

Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):238-245. doi: 10.1016/j.clml.2020.10.005. Epub 2020 Oct 8.

DOI:10.1016/j.clml.2020.10.005

PMID:33132101

Abstract

BACKGROUND

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Recent advances in immunotherapy have resulted in the development of chimeric antigen receptor-modified T-cell (CAR-T) therapy, such as axicabtagene ciloleucel (axi-cel). However, axi-cel administration is not without risks of toxicity.

PATIENTS AND METHODS

This retrospective study of 37 patients with relapsed or refractory diffuse large B-cell lymphoma evaluated the incidence and severity of common and severe safety events after axi-cel treatment in a real-world setting. Ninety percent of patients had received 3 or more prior lines of therapy (median prior therapies 3, range 2-7) before receiving CAR-T therapy, and 32.4% had relapsed after prior stem-cell transplantation.

RESULTS

All but one patient experienced cytokine release syndrome (CRS) of any grade (97.3%). Of those 36 patients, 83.3% experienced maximum CRS grade of 1 or 2, occurring after a median of 27 hours and persisting for a median of 6 days. Twenty-seven patients (73.0%) experienced neurotoxicity of any grade. Of those 27 patients, 96.3% experienced maximum neurotoxicity grade of 2 or higher, occurring after a median of 145 hours (6 days) and persisting for a median of 7 days. All 10 patients aged 65 or older had neurotoxicity of grade 2 or higher, compared to 59.3% (11/27) under age 65 (P = .02). Patients with baseline Eastern Cooperative Oncology Group performance status score of 2 were significantly more likely to have shorter time to neurotoxicity compared to patients with performance status of 0 (P = .01).

CONCLUSION

With more real-life experience and data, we will be able to define and refine management of toxicities unique to CAR-T therapy.

摘要

背景

弥漫性大 B 细胞淋巴瘤是最常见的非霍奇金淋巴瘤类型。免疫疗法的最新进展催生了嵌合抗原受体修饰 T 细胞（CAR-T）疗法，如 axi-cel。然而，axi-cel 的应用并非没有毒性风险。

患者与方法

本项对 37 例复发性或难治性弥漫性大 B 细胞淋巴瘤患者的回顾性研究，评估了 axi-cel 治疗在真实环境下的常见和严重安全事件的发生率和严重程度。90%的患者在接受 CAR-T 治疗前接受了 3 种或以上的先前治疗（中位数 3 种，范围 2-7），32.4%的患者在干细胞移植后复发。

结果

除 1 例患者外，所有患者均发生了任何等级的细胞因子释放综合征（CRS）（97.3%）。在这 36 例患者中，83.3%的患者出现了 1 或 2 级的最大 CRS，发生时间中位数为 27 小时，持续时间中位数为 6 天。27 例（73.0%）患者发生了任何等级的神经毒性。在这 27 例患者中，96.3%的患者出现了 2 级或更高级别的最大神经毒性，发生时间中位数为 145 小时（6 天），持续时间中位数为 7 天。所有 10 例年龄在 65 岁或以上的患者均发生了 2 级或更高级别的神经毒性，而年龄在 65 岁以下的患者（27 例）为 59.3%（11/27）（P=0.02）。与表现状态为 0 的患者相比，基线东部肿瘤协作组表现状态评分为 2 的患者发生神经毒性的时间明显更短（P=0.01）。