Guillaume Manson, Roberta Di Blasi, Roch Houot, Franck Morschhauser, Guillaume Cartron, Thomas Gastinne, Didier Blaise, François-Xavier Gros, Pierre Bories, Fabien Le Bras, Marie-Thérèse Rubio, Mohammad Mohty, Jacques-Olivier Bay, Stéphanie Guidez, Cristina Castilla Llorente, Fabrice Jardin, Amandine Durand, Blandine Guffroy, Michaël Loschi, Laurianne Drieu La Rochelle, Julie Abraham, Adrien Chauchet, Laura Herbreteau, Sylvain Choquet, Magalie Joris, Sylvain Carras, Gandhi-Laurent Damaj, Justine Decroocq, Tanguy-Schmidt Aline, Olivier Hermine, Emmanuelle Nicolas-Virelizier, Elodie Gat, Steven Le Gouill, Emmanuel Bachy, Remy Dulery
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.