Outcomes and salvage strategies for large B‐cell lymphoma progressing after second‐line CAR T‐cell therapy: A DESCAR‐T study from the LYSA group

Relapse after chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) is associated with a dismal prognosis. Although Phase 3 trials have established CAR T-cells as standard second-line (2L) therapy, outcomes and optimal management after relapse in this setting remain unknown because no real-world data are currently available. We conducted a multicenter retrospective study using the French DESCAR-T registry, including patients with LBCL who relapsed after 2L CAR T-cell therapy with axicabtagene ciloleucel or lisocabtagene maraleucel. The objective was to describe postrelapse treatments, outcomes, and prognostic factors. Among the 893 patients treated with 2L CAR T-cells, 297 (33%) relapsed and were analyzed. Median time to relapse was 2.7 months, with 35% of these relapses occurring within 2 months. Among the 231 treated patients, bispecific antibody (BsAb)-based regimens were the most common type of salvage therapy (65%). The overall response rate after relapse was 39.1%, with a complete response rate of 27.6%. Notably, despite the use of BsAb-based therapy in 65% of patients, the median overall survival (OS2) after relapse was only 6.5 months (median progression-free survival [PFS2]: 3.4 months). Patients treated with BsAb monotherapy achieved a median OS of 7.1 months. Multivariate analysis revealed that early relapse (<6 months), an Eastern Cooperative Oncology Group (ECOG) ≥ 2, and an elevated C-reactive protein (≥30 mg/L) were independently associated with poor OS. This study represents the first real-world analysis of outcomes after relapse following 2L CAR T-cell therapy. Despite the more frequent incorporation of BsAbs into the therapeutic landscape, overall prognosis and treatment efficacy remain dismal, highlighting the urgent need for innovative therapeutic strategies and dedicated prospective trials in this emerging double-refractory population.

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Journal
HemaSphere
Published
2026-05-01
DOI
https://doi.org/10.1002/hem3.70356
Primary Topic
CAR-T cell therapy research
Type
article
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article

Outcomes and salvage strategies for large B‐cell lymphoma progressing after second‐line CAR T‐cell therapy: A DESCAR‐T study from the LYSA group

Jérôme Paillassa, Emelie Van Zele, Steven Le Gouill, Pierre Bories et al.
HemaSphere
CAR-T cell therapy research
article

Outcomes and salvage strategies for large B‐cell lymphoma progressing after second‐line CAR T‐cell therapy: A DESCAR‐T study from the LYSA group

Jérôme Paillassa, Emelie Van Zele, Steven Le Gouill, Pierre Bories, Luc‐Matthieu Fornecker, Adrien Chauchet, Antoine Capes, Guillaume Manson, Fabien Claves, Laura Herbreteau, Benoît Tessoulin, Justine Decroocq, Axel André, François‐Xavier Gros, Julie Abraham, Ludovic Fouillet, Laurianne Drieu La Rochelle, Vivien Dupont, C Thieblemont, Michael Loschi, Cedric Rossi, Stephanie Guidez, Jacques‐Olivier Bay, Roch Houot, Jean‐Valère Malfuson, Pierre Sesques, Gandhi Damaj, Marie‐Thérèse Rubio, Hadia Hafirassou, Magalie Joris, Sylvain Choquet, Olivier Hermine, Vincent Camus, Gabriel Brisou, Guillaume Cartron, Franck Morschhauser, Laure Lebras, Cristina Castilla‐Llorente
article en

Abstract

Relapse after chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) is associated with a dismal prognosis. Although Phase 3 trials have established CAR T-cells as standard second-line (2L) therapy, outcomes and optimal management after relapse in this setting remain unknown because no real-world data are currently available. We conducted a multicenter retrospective study using the French DESCAR-T registry, including patients with LBCL who relapsed after 2L CAR T-cell therapy with axicabtagene ciloleucel or lisocabtagene maraleucel. The objective was to describe postrelapse treatments, outcomes, and prognostic factors. Among the 893 patients treated with 2L CAR T-cells, 297 (33%) relapsed and were analyzed. Median time to relapse was 2.7 months, with 35% of these relapses occurring within 2 months. Among the 231 treated patients, bispecific antibody (BsAb)-based regimens were the most common type of salvage therapy (65%). The overall response rate after relapse was 39.1%, with a complete response rate of 27.6%. Notably, despite the use of BsAb-based therapy in 65% of patients, the median overall survival (OS2) after relapse was only 6.5 months (median progression-free survival [PFS2]: 3.4 months). Patients treated with BsAb monotherapy achieved a median OS of 7.1 months. Multivariate analysis revealed that early relapse (<6 months), an Eastern Cooperative Oncology Group (ECOG) ≥ 2, and an elevated C-reactive protein (≥30 mg/L) were independently associated with poor OS. This study represents the first real-world analysis of outcomes after relapse following 2L CAR T-cell therapy. Despite the more frequent incorporation of BsAbs into the therapeutic landscape, overall prognosis and treatment efficacy remain dismal, highlighting the urgent need for innovative therapeutic strategies and dedicated prospective trials in this emerging double-refractory population.

HemaSphereVol. 10(5)
Hôpital Necker-Enfants Malades (FR), Inserm (FR), Université de Versailles Saint-Quentin-en-Yvelines (FR), Centre Hospitalier Universitaire de Grenoble (FR), Institut Gustave Roussy (FR), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Université de Poitiers (FR), Sorbonne Université (FR), Centre Hospitalier Universitaire de Besançon (FR), Institut de Cancérologie Strasbourg (FR), Hôpital Cochin (FR), Centre Hospitalier Universitaire de Montpellier (FR), Centre Hospitalier Universitaire de Tours (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Hôpital Bretonneau (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hôpital Saint-Antoine (FR), Centre Léon Bérard (FR), The Lymphoma Academic Research Organisation (FR), Centre Hospitalier Universitaire de Poitiers (FR), Centre Hospitalier Universitaire d'Angers (FR), Centre Hospitalier Universitaire de Caen Normandie (FR), CHU Dijon Bourgogne (FR), Hôpital l'Archet (FR), Pitié-Salpêtrière Hospital (FR), Hôpital Pontchaillou (FR), Neurocentre Magendie (FR), Centre d'Investigation Clinique de Nantes (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Hôpitaux Universitaires Henri-Mondor (FR), Centre Hospitalier Régional Universitaire de Brest (FR), Hôpital d'instruction des Armées Percy (FR), Hôpital Saint-Louis (FR), Institut Paoli-Calmettes (FR), Hôpital Claude Huriez (FR), Centre Hospitalier Universitaire de Rennes (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), Hôpital Dupuytren (FR), Hôpital Albert Michallon (FR), Centre Henri Becquerel (FR), Université d'Angers (FR), Institut Curie (FR), Université de Caen Normandie (FR)
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