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

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). This work is, to our knowledge, the first study describing LBCL patients with LF after CAR T-cells. bsAb seem to be more effective compared with other strategies in the LF setting and this should be considered in the design of new clinical trials.

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Journal
Blood Advances
Published
2025-10-22
DOI
https://doi.org/10.1182/bloodadvances.2025016727
Citations
1
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
1.05

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article

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

Elodie Gat, Gabriel Brisou, Blandine Guffroy, Aline Schmidt et al.
1 citations
Blood Advances
CAR-T cell therapy research
1.05
article

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

Elodie Gat, Gabriel Brisou, Blandine Guffroy, Aline Schmidt, Fabrice Jardin, Michael L. Loschi, Sylvain Choquet, Steven Le Gouill, Roberta Di Blasi, Pierre Bories, Magalie Joris, Gaëlle Guillerm, Adrien Chauchet, Roch Houot, Guillaume Cartron, Cristina Castilla‐Llorente, Stéphanie Guidez, Franck Morschhauser, Arnaud Campidelli, Olivier Tournilhac, Emmanuel Bachy, Guillaume Manson, Olivier Casasnovas, Fabien Claves, Federico Erbella, Olivier Hermine, Sylvain Carras, Benoît Tessoulin, Emmanuel Gyan, Laure Ricard, Justine Decroocq, Louise Roulin, François‐Xavier Gros, Julie Abraham
article en
1 citations

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). This work is, to our knowledge, the first study describing LBCL patients with LF after CAR T-cells. bsAb seem to be more effective compared with other strategies in the LF setting and this should be considered in the design of new clinical trials.

Blood AdvancesVol. 10(2)
Université Claude Bernard Lyon 1 (FR), Hôpital Necker-Enfants Malades (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université de Bourgogne (FR), Université Paris Cité (FR), Institut National Polytechnique de Toulouse (FR), Université de Lille (FR), Centre Hospitalier Universitaire de Grenoble (FR), Institut Gustave Roussy (FR), Saint Louis University Hospital (US), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire de Nantes (FR), Université Rennes 2 (FR), Sorbonne Université (FR), Institut de Chimie de Nice (FR), Centre Hospitalier Universitaire de Besançon (FR), Institut de Cancérologie Strasbourg (FR), Lille’s Cardiology Hospital (FR), Hôpital Cochin (FR), Centre Hospitalier Universitaire de Montpellier (FR), Centre Hospitalier Universitaire de Tours (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hospices Civils de Lyon (FR), Hôpital Saint-Antoine (FR), University of Clermont Auvergne (FR), Institut de Cancérologie de l'Ouest (FR), The Lymphoma Academic Research Organisation (FR), Centre Hospitalier Universitaire de Poitiers (FR), Centre Hospitalier Universitaire d'Angers (FR), Hôpital Lyon Sud (FR), CHU Dijon Bourgogne (FR), Centre Hospitalier Universitaire de Limoges (FR), Pitié-Salpêtrière Hospital (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Hôpitaux Universitaires Henri-Mondor (FR), Centre Hospitalier Régional Universitaire de Brest (FR), Centre de Recherche Saint-Antoine (FR), Laboratoire National Henri Becquerel (FR), Institut Cochin (FR), Hôpital Universitaire Dupuytren (FR), Hôpital Saint-Louis (FR), Institut des Hautes Études du Ministère de l'Intérieur (FR), Lymphoma Study Association (FR), Institut Paoli-Calmettes (FR), Centre Hospitalier Universitaire de Rennes (FR), Centre Henri Becquerel (FR), Université Paris 1 Panthéon-Sorbonne (FR), Université de Rennes (FR), Institut Curie (FR), Université Grenoble Alpes (FR), Nantes Université (FR)
Amgen, Bristol-Myers Squibb, Gilead Sciences, Celgene, Incyte
Openalex Percentile: Top 17%
CAR-T cell therapy research
1.05
DOIOpen Access PDFOpenAlex
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