氟达拉滨与环磷酰胺 (FC) 联合使用是 CAR T 细胞疗法 (CAR T) 的标准淋巴细胞清除方案。 2022 年，全国氟达拉滨短缺，需要探索替代方案，尽管缺乏临床安全性和有效性数据，但许多中心仍采用单药苯达莫司汀作为淋巴细胞清除剂。为了填补文献中的这一空白，我们在 axicabtagene ciloleucel (axi-cel) 治疗之前评估了苯达莫司汀作为淋巴清除的安全性、有效性和扩张动力学。 84 名连续接受 axi-cel 治疗的复发或难治性大 B 细胞淋巴瘤患者并在斯坦福大学采用统一的毒性管理计划进行了研究。 27 名患者接受苯达莫司汀替代性淋巴细胞清除术，57 名患者接受 FC。最佳完全缓解率相似（FC 为 73.7%，苯达莫司汀为 74%，p=0.28），并且 12 个月无进展生存期或总生存期没有显着差异估计值（分别为 p=0.17  和 p=0.62）。两个队列中高级细胞因子释放综合征和免疫效应细胞相关神经毒性综合征的发生率相似。苯达莫司汀队列的血液学毒性和中性粒细胞减少性发热的抗生素使用比例较低。通过细胞免疫的定量评估来测量，苯达莫司汀队列的免疫重建优于 FC 队列。通过峰值扩增和扩增曲线下面积测量的 CAR T 扩增在队列之间具有可比性。苯达莫司汀是 axi-cel 的一种安全有效的替代性淋巴清除调理方法，具有较低的早期血液学毒性和有利的免疫重建。© 作者（或）他们的雇主）2024。根据 CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy.84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC.Best complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts.Bendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.