Response kinetics following CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry

Response kinetics after CAR T-cell therapy remain poorly characterized. In this nationwide real-world evidence study using the French DESCAR-T registry (NCT04328298), we analyzed outcomes in 1542 adults with large B-cell lymphoma treated with CAR T cells after ≥2 prior therapies. At one month (M1), 49.1% achieved complete remission (CR), 28.9% partial response (PR), 6.1% stable disease (SD), and 15.9% progressive disease. Median event-free survival (EFS) at M1 was 22.3 months for CR, 3.5 for PR, and 2.3 for SD (p < 0.001). Among 484 patients with incomplete response (PR/SD) at M1, 35.5% subsequently converted to CR, mostly within 6 months. These conversions were associated with response duration and overall survival (OS) comparable to sustained early CR. Multivariate analyses identified age >65 years, lack of response to bridging therapy, and tisagenlecleucel use as independent predictors of lower CR conversion, shorter EFS, and reduced OS. A prognostic score combining these factors stratified PR/SD patients into four risk groups with distinct outcomes. In conclusion, an incomplete response at M1 should not automatically prompt watch-and-wait. Although over one-third convert to CR with favorable outcomes, most progress or die and may require early intervention. These findings support risk-adapted post-infusion management and inform future prospective trials. CLINICAL TRIAL REGISTRATION: The DESCAR-T registry is registered under ClinicalTrials.gov identifier NCT04328298.