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Publications

Journal Article Epublish

PubMed: 42099680 DOI: 10.1002/hem3.70356

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.

Hemasphere 10(5):e70356

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

Affiliations

  • CHU de Lyon Lyon France.
  • CHU de Rennes - Hôpital Pontchaillou Rennes France.
  • CHU de Montpellier Montpellier France.
  • CHU de Bordeaux - Centre François Magendie Bordeaux France.
  • CHU de Lille - Hôpital Claude Huriez Lille France.
  • Institut Gustave Roussy Villejuif France.
  • Institut Paoli-Calmettes, Marseille Marseille France.
  • Institut Universitaire du Cancer de Toulouse - Oncopole Toulouse France.
  • AP-HP - Hôpital Saint-Louis Paris France.
  • CHU de Tours - Hôpital Bretonneau Tours France.
  • CHU de Nantes - Hôtel-Dieu, Nantes Nantes France.
  • AP-HP - Hôpital Henri Mondor Créteil France.
  • CHU de Dijon - Hôpital François Mitterrand Dijon France.
  • CHU d'Angers, Angers Angers France.
  • CHU de Poitiers, Poitiers Poitiers France.
  • AP-HP - Hôpital Saint-Antoine Paris France.
  • CHU de Brest - Hôpital Morvan Brest France.
  • AP-HP - Hôpital Pitié-Salpêtrière Paris France.
  • CHU Estaing, Clermont-Ferrand, Clermont-Ferrant France.
  • CHU de Besançon - Hôpital Jean Minjoz Besancon France.
  • Centre Léon Bérard, Lyon Lyon France.
  • CHU de Grenoble - HôpitalAlbert Michallon Grenoble France.
  • CHU de Limoges - Hôpital Dupuytren Limoges France.
  • Hôpital d'Instruction des Armées Percy, Clamart Clamart France.
  • CHU de Nancy - Hôpital de Brabois Nancy France.
  • AP-HP - Hôpital Cochin Paris France.
  • Institut de Cancérologie Strasbourg Europe (ICANS) Strasbourg France.
  • CHU de Caen - Côte de Nacre - Institut d'Hématologie de Basse-Normandie (IHBN) Caen France.
  • Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne (I.CHU.SE) St Etienne France.
  • CHU d'Amiens - Hôpital Sud Amiens France.
  • CHU de Nice - Hôpital de l'Archet Nice France.
  • AP-HP - Hôpital Necker Paris France.
  • LYSARC Lyon France.
  • Service d'hématologie, Institut Curie Saint Cloud France.
  • Université de Versailles Saint-Quentin Versailles France.
  • Laboratoire d'Imagerie Translationnelle en Oncologie, U1288 INSERM/Institut Curie Centre de Recherche Paris France.
  • Centre Henri Becquerel Rouen France.

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.

MeSH

Cells, Lymphoma, B-Cell, Lymphoma, Therapeutics, T-Lymphocytes, B-Lymphocytes, Prognosis, Car-T Cell