Late failure of aggressive B-cell lymphoma after CAR T-cell therapy: a LYSA study from the DESCAR-T registry

作者：Federico Erbella, Emmanuel Bachy, Guillaume Cartron, Elodie Gat, Guillaume Manson, Franck Morschhauser, François‐Xavier Gros, Louise Roulin, Benoît Tessoulin, Pierre Bories, Olivier Tournilhac, Laure Ricard, Stéphanie Guidez, Sylvain Choquet, Olivier Casasnovas, Gabriel Brisou, Arnaud Campidelli, Cristina Castilla‐Llorente, Fabrice Jardin, Emmanuel Gyan, Blandine Guffroy, Julie Abraham, Justine Decroocq, Adrien Chauchet, Magalie Joris, Fabien Claves, Sylvain Carras, Gaëlle Guillerm, Michaël Loschi, Olivier Hermine, Aline Taguy-Schimidt, Steven Le Gouill, Roch Houot, Roberta Di Blasi · 发表于：Blood Advances · 年份：2025 · DOI：10.1182/bloodadvances.2025016727 · 被引用次数：7 · 研究领域：CAR-T cell therapy research、Silicon Carbide Semiconductor Technologies、Integrated Circuits and Semiconductor Failure Analysis

ABSTRACT: Large B-cell lymphoma (LBCL) patients failing anti-CD19 chimeric antigen receptor (CAR) T-cell therapy exhibit poor prognosis. Most progressions/relapses occur within 3 months from infusion whereas only a few events occur thereafter (late failure, [LF]). We analyze features, treatments, and outcomes of patients with LF from DESCAR-T, a nationwide registry collecting real-life data for patients treated with approved CAR T-cell therapy in France. Between July 2018 and March 2024, 298 (39.9%) LBCL LF patients (median age, 62 years [range, 18-79]; male, 61.7%) were collected from DESCAR-T. Most patients had diffuse LBCL (n = 205 [68.8%]), advanced stage disease (84.6%), and age-adjusted International Prognostic Index of 2 to 3 (59.3%) at CAR T-cell eligibility. After failure, 76.5% of patients received a systemic therapy and overall response rate was 22.6% (complete response, 18%). At a median follow-up since first LF event of 13.8 months (95% confidence interval [CI], 12.1-15.4), the median overall survival and progression-free survival 2 (PFS-2) were 4.4 (95% CI, 3.8-5.8) and 13.2 (95% CI, 9.6-18) months, respectively. Compared with chemotherapy (hazard ratio [HR], 0.350; 95% CI, 0.193-0.633) and with pooled other treatment groups (HR, 0.483; 95% CI, 0.290-0.805), salvage treatment with bispecific antibodies (bsAb) after CAR T-cell failure showed better PFS-2. Radiotherapy obtained prolonged responses in some patients with 12-month PFS-2 of 41.5% (95% CI, 22.5-59.5). ...