Rao Uttam K, Majhail Navneet S, Blunk Betsy, Abernathy Karin, Bachier Carlos, Bhushan Vikas, Cruz Jose Carlos, Elayan Mohammed, Gregory Tara, LeMaistre Charles F, Malik Shahbaz A, Martin Casey, Mattlin Meredith, Blade Gabrielle, Maris Michael B, Mathews John, Mountjoy Luke, Pantin Jeremy M, Ramakrishnan Aravind, Shaughnessy Paul, Tees Michael T, Vance Estil A, Zoghi Behyar, Battiwalla Minoo
Sarah Cannon Transplant and Cellular Therapy Network, St. David's South Austin Medical Center, Austin, Texas.
Sarah Cannon Transplant and Cellular Therapy Network, TriStar Centennial Medical Center, Nashville, Tennessee.
Transplant Cell Ther. 2025 Aug;31(8):549.e1-549.e11. doi: 10.1016/j.jtct.2025.03.012. Epub 2025 Mar 22.
Chimeric antigen receptor T-cell (CAR-T) therapy represents a transformative advance in treating relapsed/refractory non-Hodgkin lymphomas (NHLs). Effective pre-infusion lymphodepleting chemotherapy (LDC) is essential for optimizing CAR-T outcomes. Traditionally, a combination of fludarabine and cyclophosphamide (Flu/Cy) has been used; however, a global fludarabine shortage warranted a search for alternative regimens. This study compares the efficacy and safety of bendamustine versus Flu/Cy as LDC in NHL patients.
The purpose of this study was to compare the efficacy and safety of bendamustine versus Flu/Cy as LDC regimens in patients with relapsed/refractory NHL undergoing CAR-T therapy. We hypothesized that bendamustine would offer comparable outcomes to Flu/Cy while providing logistical advantages in outpatient settings.
This retrospective analysis evaluated 265 NHL patients treated with FDA-approved CAR-T products from January 2018 to October 2023. Outcomes included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic recovery, progression-free survival (PFS), overall survival (OS), and healthcare resource utilization. Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were employed to adjust for CAR-T product type, infusion year, disease subtype, and dexamethasone prophylaxis.
Both LDC regimens effectively prepared patients for CAR-T therapy, with no significant differences in CRS, ICANS, OS, or PFS. At one year, OS was 71% for bendamustine versus 68% for Flu/Cy, and PFS was 68% versus 60% (P = .3 and P = .4, respectively). Bendamustine was associated with less severe hematologic toxicity; ANC levels did not fall below 0.5 K/µL in 71% of bendamustine recipients compared to 17% for Flu/Cy (P < .001). Multivariable analysis identified infusion year as a significant predictor of OS (HR 0.77, P = .008) and PFS (HR 2.6, P < .001), reflecting improvements in CAR-T practices over time.
Bendamustine is a viable alternative to Flu/Cy for LDC prior to CAR-T therapy in relapsed/refractory NHL, as it demonstrates comparable efficacy and safety. Its operational advantages, including reduced hospitalization rates and suitability for outpatient administration, underscore its potential in diverse clinical settings. Prospective studies are needed to confirm long-term outcomes and further optimize LDC strategies.
嵌合抗原受体T细胞（CAR-T）疗法是治疗复发/难治性非霍奇金淋巴瘤（NHL）的一项变革性进展。有效的预输注淋巴细胞清除化疗（LDC）对于优化CAR-T治疗效果至关重要。传统上，使用氟达拉滨和环磷酰胺（Flu/Cy）联合方案；然而，全球氟达拉滨短缺促使人们寻找替代方案。本研究比较了苯达莫司汀与Flu/Cy作为NHL患者LDC的疗效和安全性。
本研究的目的是比较苯达莫司汀与Flu/Cy作为LDC方案在接受CAR-T治疗的复发/难治性NHL患者中的疗效和安全性。我们假设苯达莫司汀将提供与Flu/Cy相当的疗效，同时在门诊环境中具有后勤优势。
这项回顾性分析评估了2018年1月至2023年10月期间接受FDA批准的CAR-T产品治疗的265例NHL患者。结局指标包括细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征（ICANS）、血液学恢复、无进展生存期（PFS）、总生存期（OS）和医疗资源利用情况。采用Kaplan-Meier生存分析和多变量Cox比例风险模型来调整CAR-T产品类型、输注年份、疾病亚型和地塞米松预防措施。
两种LDC方案均有效地为患者接受CAR-T治疗做好了准备，在CRS、ICANS、OS或PFS方面无显著差异。一年时，苯达莫司汀组的OS为71%，Flu/Cy组为68%；PFS分别为68%和60%（P值分别为0.3和0.4）。苯达莫司汀与较轻的血液学毒性相关；71%接受苯达莫司汀治疗的患者中性粒细胞绝对值水平未降至0.5×10⁹/L以下，而Flu/Cy组为17%（P<0.001）。多变量分析确定输注年份是OS（风险比0.77，P=0.008）和PFS（风险比2.6，P<0.001）的显著预测因素，这反映了随着时间推移CAR-T治疗实践的改进。
对于复发/难治性NHL患者，在CAR-T治疗前进行LDC时，苯达莫司汀是Flu/Cy的可行替代方案，因为它具有相当的疗效和安全性。其操作优势，包括降低住院率和适合门诊给药，突出了其在不同临床环境中的潜力。需要进行前瞻性研究以确认长期结局并进一步优化LDC策略。
