Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan
Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan
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DOI：
10.1111/bjh.18831
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发表时间：
2023-04-25
影响因子：
6.5
通讯作者：
Arai, Yasuyuki
中科院分区：
文献类型：
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作者：
Jo, Tomoyasu;Yoshihara, Satoshi;Arai, Yasuyuki
对于成功的嵌合抗原受体T(CAR-T)细胞治疗，CAR-T细胞的制造必须不会因次优扩增而导致失败。为了确定CAR-T细胞生产失败的危险因素，我们在日本进行了一项全国性的队列研究，并分析了接受组织集落细胞生产的弥漫性大B细胞淋巴瘤(DLBCL)患者。我们比较了30例失败(7.4%)和378例成功(n=378)的临床因素。在失败患者中，曾接受苯达莫司汀治疗的患者比例(43.3%vs.14.8%；p<；0.001)显著高于成功组，其外周血中血小板计数(12.0vs.17.0×10(4)/亩L；p=0.01)和CD_4/CD_8T细胞比率(0.30vs.0.56；p<；0.01)显著低于成功组。多因素分析显示，换血前重复使用苯达莫司汀的洗脱期较短(OR值为5.52；P=0.013，洗脱期为3-24个月的6个周期；洗脱期为3-24个月的OR57.09；P=0.005
For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 x 10(4)/mu L; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for >= 6 cycles with washout period of 3-24 months; OR, 57.09; p = 0.005 for >= 3 cycles with washout period of