肿瘤细胞治疗研究
英文原题：Impact of Prior Bendamustine Exposure on Chimeric Antigen Receptor T-Cell Therapy Outcomes in Follicular Lymphoma.
Impact of Prior Bendamustine Exposure on Chimeric Antigen Receptor T-Cell Therapy Outcomes in Follicular Lymphoma.
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既往苯达莫司汀暴露会损害T细胞适应性，并已在大B细胞淋巴瘤中与较差的CAR-T 细胞治疗结局相关，但缺乏滤泡性淋巴瘤（FL）特异性数据。利用TriNetX研究网络（107家医疗机构），我们对接受CD19靶向CAR-T 细胞治疗（axicabtagene ciloleucel、lisocabtagene maraleucel或tisagenlecleucel）的复发/难治性FL成人患者进行了一项回顾性队列研究。倾向评分匹配比较按苯达莫司汀暴露时间分层评估总生存期（OS）。与未暴露于苯达莫司汀的患者相比，任何既往苯达莫司汀暴露均与较差的2年OS相关（58.99%对76.73%；HR 1.855，95% CI 1.003至3.432，P = .046，n = 89）。
关键的是，与暴露时间超过1年前相比，CAR-T 细胞输注前1年内苯达莫司汀暴露与显著更差的2年OS相关（40%对68%；HR 2.277，95% CI 1.117至4.644；P = .020，n = 46）。相比之下，CAR-T 细胞治疗前苯达莫司汀暴露超过1年的患者与未暴露于苯达莫司汀的患者OS相同（71%对72%；HR 1.045；P = .914）。剂量-反应分析表明，随着苯达莫司汀暴露时间接近CAR-T 细胞输注，死亡风险在所有3项关联指标中均呈现一致且具有统计学意义的增加（P < .05）。近期苯达莫司汀暴露的患者在CAR-T 细胞治疗后30、60和90天内的住院率显著更高。这些发现具有假设生成性，提示一个临床上可操作的12个月洗脱间期，并支持在可能未来需要CAR-T 细胞治疗的FL患者中优先使用不含苯达莫司汀的方案而非以苯达莫司汀为基础的方案。
Prior bendamustine exposure impairs T-cell fitness and has been associated with inferior CAR T-cell therapy outcomes in large B-cell lymphoma, but follicular lymphoma (FL)-specific data are lacking. Using the TriNetX Research Network (107 healthcare organizations), we conducted a retrospective cohort study of adult patients with relapsed/refractory FL who received CD19-directed CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, or tisagenlecleucel). Propensity score-matched comparisons evaluated overall survival (OS) stratified by bendamustine exposure timing. Any prior bendamustine exposure was associated with inferior 2-yr OS compared with bendamustine-naive patients (58. 99% versus 76. 73%; HR 1. 855, 95% CI 1. 003 to 3. 432, P = .
046, n = 89). Critically, bendamustine exposure within 1 yr of CAR T-cell infusion was associated with significantly worse 2-yr OS compared with exposure more than 1 yr prior (40% versus 68%; HR 2. 277, 95% CI 1. 117 to 4. 644; P = . 020, n = 46). In contrast, patients with bendamustine exposure more than 1 yr before CAR T-cell had the same OS as bendamustine-naive patients (71% versus 72%; HR 1.
045; P = . 914). A dose-response analysis demonstrated a consistent, statistically significant increase in mortality risk as bendamustine exposure approached the time of CAR T-cell infusion across all 3 measures of association (P < . 05). Inpatient admission within 30, 60, and 90 days of CAR T-cell was significantly higher in patients with recent bendamustine exposure.
These findings are hypothesis-generating and suggest a clinically actionable 12-mo washout interval and support preferential use of nonbendamustine-containing regimens over bendamustine-based regimens in patients with FL who may require future CAR T-cell therapy.
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