Outcome of patients with mantle cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T study by LYSA Group

Brexucabtagene autoleucel (brexu-cel) is the anti-CD19 chimeric antigen receptor CAR T-cell (CAR-T) therapy approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL). Our study, conducted in the scope of the French DESCAR-T registry, aimed to analyze outcomes of MCL after brexu-cel failure. In the DESCAR-T registry, 178 patients with R/R MCL received brexu-cel. After a median follow-up (FU) of 14.5 months, 61 experienced failures. This study analyzes post- CAR-T failure progression-free survival (PFS2) and overall survival (OS2), according to clinical characteristics and salvage treatments. At infusion, 36% of patients had a high MCL International Prognostic Index score, 76.2% a Ki-67 index of ≥30%, 30.2% a TP53 mutation, and 31.6% a blastoid variant. After a median FU of 15 months following failure, median OS2 and PFS2 were 5.8 and 1.8 months, respectively. Patients experiencing early failure (<3 months) had a median OS2 of 1.8 months, compared with 6.7 and 9 months for those relapsing within 3 to 6 and after 6 months, respectively. Forty-nine patients received salvage therapy: 16 lenalidomide with/without rituximab (Len/R2), 13 immunochemotherapy (ICT), 8 Bruton tyrosine kinase inhibitor with/without venetoclax (BTKi/Ven), 7 bispecific T-cell engagers (TCEs), 3 another targeted therapy, and 2 received radiation. Overall, post salvage response rate (ORR) was 20%. One-year OS2 was 36% for patients treated with Len/R2 and ICT, 57% for TCEs, and 0% for other types of salvage. Notably, none of the TCE responders have relapsed to date (duration of response : 100%). Our series highlights the poor outcomes of patients with MCL after CAR-T failure and suggests a potential benefit of bispecific antibodies in this population.

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Publication Details

Journal
Blood Advances
Published
2025-09-30
DOI
https://doi.org/10.1182/bloodadvances.2025017234
Citations
2
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
2.09

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article

Outcome of patients with mantle cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T study by LYSA Group

Gabriel Brisou, Elodie Gat, Loïc Ysebaert, Steven Le Gouill et al.
2 citations
Blood Advances
CAR-T cell therapy research
2.09
article

Outcome of patients with mantle cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T study by LYSA Group

Gabriel Brisou, Elodie Gat, Loïc Ysebaert, Steven Le Gouill, Morgane Cheminant, Roch Houot, Catherine Thiéblemont, Clémentine Sarkozy, Charles Herbaux, Stéphanie Guidez, Amandine Fayard, Olivier Hermine, Krimo Bouabdallah, Alessandro Cuozzo, Benoît Tessoulin, Violaine Safar, Laure Ricard, Louise Roulin, M. Aymard
article en
2 citations

Abstract

Brexucabtagene autoleucel (brexu-cel) is the anti-CD19 chimeric antigen receptor CAR T-cell (CAR-T) therapy approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL). Our study, conducted in the scope of the French DESCAR-T registry, aimed to analyze outcomes of MCL after brexu-cel failure. In the DESCAR-T registry, 178 patients with R/R MCL received brexu-cel. After a median follow-up (FU) of 14.5 months, 61 experienced failures. This study analyzes post- CAR-T failure progression-free survival (PFS2) and overall survival (OS2), according to clinical characteristics and salvage treatments. At infusion, 36% of patients had a high MCL International Prognostic Index score, 76.2% a Ki-67 index of ≥30%, 30.2% a TP53 mutation, and 31.6% a blastoid variant. After a median FU of 15 months following failure, median OS2 and PFS2 were 5.8 and 1.8 months, respectively. Patients experiencing early failure (<3 months) had a median OS2 of 1.8 months, compared with 6.7 and 9 months for those relapsing within 3 to 6 and after 6 months, respectively. Forty-nine patients received salvage therapy: 16 lenalidomide with/without rituximab (Len/R2), 13 immunochemotherapy (ICT), 8 Bruton tyrosine kinase inhibitor with/without venetoclax (BTKi/Ven), 7 bispecific T-cell engagers (TCEs), 3 another targeted therapy, and 2 received radiation. Overall, post salvage response rate (ORR) was 20%. One-year OS2 was 36% for patients treated with Len/R2 and ICT, 57% for TCEs, and 0% for other types of salvage. Notably, none of the TCE responders have relapsed to date (duration of response : 100%). Our series highlights the poor outcomes of patients with MCL after CAR-T failure and suggests a potential benefit of bispecific antibodies in this population.

Blood AdvancesVol. 10(1)
Hôpital Necker-Enfants Malades (FR), Université de Bordeaux (FR), Université de Montpellier (FR), Institut National Polytechnique de Toulouse (FR), Saint Louis University Hospital (US), Centre Hospitalier Universitaire de Nantes (FR), Université de Poitiers (FR), Sorbonne Université (FR), Centre Hospitalier Universitaire de Montpellier (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Hospices Civils de Lyon (FR), Hôpital Saint-Antoine (FR), University of Clermont Auvergne (FR), Bordeaux Population Health (FR), The Lymphoma Academic Research Organisation (FR), Laboratoire de Thermique et Energie de Nantes (FR), Centre Hospitalier Universitaire de Poitiers (FR), Hôpital Lyon Sud (FR), Hôpital Pontchaillou (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Hôpitaux Universitaires Henri-Mondor (FR), Hôpital Saint-Louis (FR), Institut Paoli-Calmettes (FR), Laboratoire de Génétique Cellulaire (FR), Centre Hospitalier Universitaire de Rennes (FR), Institut Curie (FR), Nantes Université (FR)
Amgen, Bristol-Myers Squibb, Eli Lilly and Company, AstraZeneca, Sanofi, Gilead Sciences, Alexion Pharmaceuticals, Celgene, Regeneron Pharmaceuticals, BeiGene, Incyte, Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent, Genentech
Openalex Percentile: Top 10%
CAR-T cell therapy research
2.09
DOIOpen Access PDFOpenAlex
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