Short ramp-up glofitamab halves mortality risk after anti-CD19 CAR T-cell therapy failure in patients with diffuse large B-cell lymphoma: final results of the LYSA BiCAR phase 2 trial with a pre-specified external control arm
Abstract
Background: Failure after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in diffuse large B-cell lymphoma (DLBCL) is associated with poor survival and there is no established standard of care. We previously reported the phase 2 LYSA BiCAR trial of short-ramp-up glofitamab after CAR T-cell failure. Here, we present the final survival results and a pre-specified external comparative effectiveness analysis against a contemporary control arm constructed from academic data. Methods: BiCAR is a multicenter, single-arm trial in adults with CD20-positive DLBCL refractory to, or in first relapse/progression after anti-CD19 CAR T-cell therapy. Participants received obinutuzumab pretreatment followed by intravenous glofitamab with an accelerated step-up to 30 mg within 8 days, then 30 mg every 21 days for up to 11 cycles. For comparative analyses, we constructed an external control arm from patients included in the French DESCAR-T registry and the ALYCANTE phase 2 trial who experienced CAR T-cell failure, who subsequently started non-bispecific systemic therapy, met key BiCAR eligibility criteria, and initiated treatment within a ±1-month window around the BiCAR treatment period. To minimise datasource bias, both arms, glofitamab (BICAR) and control, were constructed from individual patient data from the DESCAR-T registry and the ALYCANTE trial. A propensity score including major prognostic variables was estimated and applied using stabilized inverse probability of treatment weighting with multiple imputation. Additional weighting schemes and restrictions were applied in sensitivity analyses, and restricted mean survival time (RMST) was evaluated by treatment arm. Results: Among 47 enrolled BiCAR patients, 46 received glofitamab. At a median follow-up of 30.4 months, median overall survival (OS) was 17.3 months, and the 2-year OS rate was 38.3%. For comparative effectiveness, 45 glofitamab-treated patients and 133 controls formed the analysis cohort. In the primary weighted analysis, median OS was 19.6 months for glofitamab and 7.6 months for controls, with a hazard ratio for death of 0.49 (95% CI, 0.31-0.79; P = 0.007). Multiple sensitivity analyses yielded consistent estimates. Glofitamab significantly improved the RMST of 5 months (P = 0.007) over a 2-year follow-up. Conclusions: In this robust comparative effectiveness study, short-ramp-up glofitamab administered at first relapse or progression after CAR T-cell failure significantly increases the chance of survival compared to contemporaneous non-bispecific salvage therapies, supporting its use as a preferred option for eligible patients with DLBCL who fail anti-CD19 CAR T-cell therapy. Trial registration: ClinicalTrials.gov identifier NCT04703686.
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BibTeX
@article{cartron2026short,
title = {{Short ramp-up glofitamab halves mortality risk after anti-CD19 CAR T-cell therapy failure in patients with diffuse large B-cell lymphoma: final results of the LYSA BiCAR phase 2 trial with a pre-specified external control arm}},
author = {Guillaume Cartron and Isabelle Chaillol and Roch Houot and Yassine Al Tabaa and Fabien Le Bras and Loic Ysebaert and Sylvain Choquet and Fabrice Jardin and Jacques-Olivier Bay and François-Xavier Gros and Franck Morschhauser and Cédric Rossi and Thomas Gastinne and Catherine Thieblemont and Magalie Joris and Laure Ricard and Caroline Régny and Laurianne Drieu La Rochelle and Pierre Feugier and Ambroise Marçais and Romain Ould-Ammar and Karin Tarte and Camille Laurent and Pierre Sesques},
journal = {Journal of Hematology and Oncology},
year = {2026},
month = sep,
doi = {10.1186/s13045-026-01816-4},
url = {https://hal.science/hal-05754445v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Short ramp-up glofitamab halves mortality risk after anti-CD19 CAR T-cell therapy failure in patients with diffuse large B-cell lymphoma: final results of the LYSA BiCAR phase 2 trial with a pre-specified external control arm
AU - Guillaume Cartron
AU - Isabelle Chaillol
AU - Roch Houot
AU - Yassine Al Tabaa
AU - Fabien Le Bras
AU - Loic Ysebaert
AU - Sylvain Choquet
AU - Fabrice Jardin
AU - Jacques-Olivier Bay
AU - François-Xavier Gros
AU - Franck Morschhauser
AU - Cédric Rossi
AU - Thomas Gastinne
AU - Catherine Thieblemont
AU - Magalie Joris
AU - Laure Ricard
AU - Caroline Régny
AU - Laurianne Drieu La Rochelle
AU - Pierre Feugier
AU - Ambroise Marçais
AU - Romain Ould-Ammar
AU - Karin Tarte
AU - Camille Laurent
AU - Pierre Sesques
PY - 2026
DA - 2026/09/18
JO - Journal of Hematology and Oncology
DO - 10.1186/s13045-026-01816-4
UR - https://hal.science/hal-05754445v1
AB - Background: Failure after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in diffuse large B-cell lymphoma (DLBCL) is associated with poor survival and there is no established standard of care. We previously reported the phase 2 LYSA BiCAR trial of short-ramp-up glofitamab after CAR T-cell failure. Here, we present the final survival results and a pre-specified external comparative effectiveness analysis against a contemporary control arm constructed from academic data. Methods: BiCAR is a multicenter, single-arm trial in adults with CD20-positive DLBCL refractory to, or in first relapse/progression after anti-CD19 CAR T-cell therapy. Participants received obinutuzumab pretreatment followed by intravenous glofitamab with an accelerated step-up to 30 mg within 8 days, then 30 mg every 21 days for up to 11 cycles. For comparative analyses, we constructed an external control arm from patients included in the French DESCAR-T registry and the ALYCANTE phase 2 trial who experienced CAR T-cell failure, who subsequently started non-bispecific systemic therapy, met key BiCAR eligibility criteria, and initiated treatment within a ±1-month window around the BiCAR treatment period. To minimise datasource bias, both arms, glofitamab (BICAR) and control, were constructed from individual patient data from the DESCAR-T registry and the ALYCANTE trial. A propensity score including major prognostic variables was estimated and applied using stabilized inverse probability of treatment weighting with multiple imputation. Additional weighting schemes and restrictions were applied in sensitivity analyses, and restricted mean survival time (RMST) was evaluated by treatment arm. Results: Among 47 enrolled BiCAR patients, 46 received glofitamab. At a median follow-up of 30.4 months, median overall survival (OS) was 17.3 months, and the 2-year OS rate was 38.3%. For comparative effectiveness, 45 glofitamab-treated patients and 133 controls formed the analysis cohort. In the primary weighted analysis, median OS was 19.6 months for glofitamab and 7.6 months for controls, with a hazard ratio for death of 0.49 (95% CI, 0.31-0.79; P = 0.007). Multiple sensitivity analyses yielded consistent estimates. Glofitamab significantly improved the RMST of 5 months (P = 0.007) over a 2-year follow-up. Conclusions: In this robust comparative effectiveness study, short-ramp-up glofitamab administered at first relapse or progression after CAR T-cell failure significantly increases the chance of survival compared to contemporaneous non-bispecific salvage therapies, supporting its use as a preferred option for eligible patients with DLBCL who fail anti-CD19 CAR T-cell therapy. Trial registration: ClinicalTrials.gov identifier NCT04703686.
SN - 1756-8722
ER -