DLBCL 患者中 CAR-T 细胞生产失败的风险因素：日本全国性调查

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 10 4 / 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 <3 months), low platelet counts (OR, 0. 495 per 10 5 / L; p = 0. 022) or low CD4/CD8 ratios (<one third) (OR, 3. 249; p = 0. 011) in peripheral blood at apheresis increased the risk of manufacturing failure.

Manufacturing failure remains an obstacle to CAR-T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk-adapted strategies may help to optimize CAR-T cell therapy for DLBCL patients.