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