Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan

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 <3 months), low platelet counts (OR, 0.495 per 10(5)/mu L; p = 0.022) or low CD4/CD8 ratios (

Automated summary

In order to determine the risk factors for CAR-T cell manufacturing failure, a nationwide cohort study was conducted in Japan on patients with DLBCL who underwent tisagenlecleucel production. The study found that previous treatment with bendamustine, low platelet counts, and low CD4/CD8 T-cell ratios were significant risk factors for manufacturing failure. Repeated use of bendamustine with short washout periods prior to apheresis, low platelet counts, and low CD4/CD8 ratios were all independently associated with an increased risk of manufacturing failure.