CAR-HEMATOTOX评分可识别出在复发或难治性MCL中接受brexucabtagene autoleucel治疗的患者，他们具有较高的血液毒性、感染并发症以及治疗结果不佳的风险。
The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL.
发表日期：2023 Aug 16
作者：
Kai Rejeski, Yucai Wang, Omar Albanyan, Javier Munoz, Pierre Sesques, Gloria Iacoboni, Lucia Lopez-Corral, Isabelle Ries, Veit L Bücklein, Razan Mohty, Martin Dreyling, Aliyah Baluch, Bijal Shah, Frederick L Locke, Georg Hess, Pere Barba, Emmanuel Bachy, Yi Lin, Marion Subklewe, Michael D Jain
来源：
AMERICAN JOURNAL OF HEMATOLOGY
摘要：
CD19靶向的CAR T细胞疗法通过使用brexucabtagene autoleucel（brexu-cel）显著改善了复发/难治性Ⅱ期缀合细胞淋巴瘤（r / r MCL）患者的治疗效果。长期的细胞减少和感染是常见且临床相关的副作用。在这项多中心观察性研究中，我们描述了103名接受brexu-cel治疗的r / r MCL患者的细胞减少和感染情况。此外，我们报告了基线CAR-HEMATOTOX（HT）评分与毒性事件、非复发性死亡率（NRM）以及无进展生存期/总生存期（PFS / OS）之间的关联。在淋巴去除治疗时，有56名患者为HTlow（评分0-1），而47名患者为HThigh（评分≥2）。HThigh队列表现出持续性的中性粒细胞减少（中位数14天 vs. 6天，p＜.001）和增加的严重感染率（30% vs. 5%，p＝.001）。总体而言，1年NRM率为10.4%，主要归因于感染，并且基线HT评分不同（高vs低：17% vs. 4.6%，p＝.04）。HThigh患者的90天完全缓解率（68% vs. 93%，p＝.002），PFS（中位数9个月 vs. 未达到，p＜.0001）和OS（中位数26个月 vs. 未达到，p＜.0001）较低。多变量分析显示，高HT评分与严重血液毒性、感染和不良的PFS / OS独立相关。总之，brexu-cel治疗后感染和血液毒性是常见的，并导致NRM。基线HT评分可以识别出治疗效果差的高风险患者。© 2023年作者。美国血液学杂志由Wiley Periodicals LLC发表。
CD19-directed CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel) has substantially improved treatment outcomes for patients with relapsed/refractory mantle cell lymphoma (r/r MCL). Prolonged cytopenias and infections represent common and clinically relevant side effects. In this multicenter observational study, we describe cytopenias and infections in 103 r/r MCL patients receiving brexu-cel. Furthermore, we report associations between the baseline CAR-HEMATOTOX (HT) score and toxicity events, non-relapse mortality (NRM), and progression-free/overall survival (PFS/OS). At lymphodepletion, 56 patients were HTlow (score 0-1) while 47 patients were HThigh (score ≥2). The HThigh cohort exhibited prolonged neutropenia (median 14 vs. 6 days, p < .001) and an increased rate of severe infections (30% vs. 5%, p = .001). Overall, 1-year NRM was 10.4%, primarily attributed to infections, and differed by baseline HT score (high vs. low: 17% vs. 4.6%, p = .04). HThigh patients experienced inferior 90-day complete response rate (68% vs. 93%, p = .002), PFS (median 9 months vs. not-reached, p < .0001), and OS (median 26 months vs. not-reached, p < .0001). Multivariable analyses showed that high HT scores were independently associated with severe hematotoxicity, infections, and poor PFS/OS. In conclusion, infections and hematotoxicity are common after brexu-cel and contribute to NRM. The baseline HT score identified patients at increased risk of poor treatment outcomes.© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.