Comparative real-world outcomes of CD19-directed CAR T-cell therapies in large B-cell lymphoma

Although 3 commercial CD19-targeted chimeric antigen receptor (CAR) T-cell therapies are available for large B-cell lymphomas (LBCLs), no randomized clinical trials have compared their efficacy and safety. In this retrospective multicenter cohort study, we evaluated real-world clinical outcomes of patients with relapsed/refractory LBCL treated with axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel). Between April 2016 and July 2024, 624 patients received CD19-targeted CAR T-cell therapies (344 axi-cel, 142 tisa-cel, and 138 liso-cel). At a median follow-up of 20.9 months, the respective estimated 2-year progression-free survival (PFS) and overall survival (OS) rates were 46% and 63% for axi-cel, 30% and 45% for tisa-cel, and 45% and 58% for liso-cel. After adjusting for potential confounders in multivariate analyses, tisa-cel was associated with inferior PFS and OS compared to axi-cel. No significant survival differences were found between liso-cel and axi-cel. Propensity score and subanalyses of patients treated in the second-line vs third-line or later settings yielded similar outcomes. Compared to axi-cel, the objective response rate at 100 days was higher for liso-cel and lower for tisa-cel. Rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hematotoxicity, and febrile neutropenia were significantly higher with axi-cel. However, no significant differences in the cumulative incidence of infections or nonrelapse mortality were found. Axi-cel was associated with faster vein-to-vein time (axi-cel, 35 days; tisa-cel, 43 days; liso-cel, 41 days) and fewer out-of-specification products (axi-cel, 2%; tisa-cel, 4%; liso-cel, 11%). These results provide insights into potential differential outcomes depending on product selection.

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Publication Details

Journal
Blood Advances
Published
2025-08-15
DOI
https://doi.org/10.1182/bloodadvances.2025016778
Citations
5
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
5.23

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article

Comparative real-world outcomes of CD19-directed CAR T-cell therapies in large B-cell lymphoma

Maria Bromberg, Emma Rabinovich, Ronit Marcus, Gunjan L. Shah et al.
5 citations
Blood Advances
CAR-T cell therapy research
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article

Comparative real-world outcomes of CD19-directed CAR T-cell therapies in large B-cell lymphoma

Maria Bromberg, Emma Rabinovich, Ronit Marcus, Gunjan L. Shah, Richard J. Lin, Xavier Deschênes‐Simard, Andrew Ip, Magdalena Corona, Jennifer Kimberly Lue, Roni Shouval, Ofrat Beyar‐Katz, Sean M. Devlin, Parastoo Bahrami Dahi, Michael Scordo, Mithat Gönen, Alexander P. Boardman, Alfredo Rivas‐Delgado, Annamaria Ballweg, M. Lia Palomba, Mohammad Alhomoud, Alejandro Luna, Miguel‐Angel Perales, Gilles Salles, Lorenzo Falchi, Abraham Avigdor
article en
5 citations

Abstract

Although 3 commercial CD19-targeted chimeric antigen receptor (CAR) T-cell therapies are available for large B-cell lymphomas (LBCLs), no randomized clinical trials have compared their efficacy and safety. In this retrospective multicenter cohort study, we evaluated real-world clinical outcomes of patients with relapsed/refractory LBCL treated with axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel). Between April 2016 and July 2024, 624 patients received CD19-targeted CAR T-cell therapies (344 axi-cel, 142 tisa-cel, and 138 liso-cel). At a median follow-up of 20.9 months, the respective estimated 2-year progression-free survival (PFS) and overall survival (OS) rates were 46% and 63% for axi-cel, 30% and 45% for tisa-cel, and 45% and 58% for liso-cel. After adjusting for potential confounders in multivariate analyses, tisa-cel was associated with inferior PFS and OS compared to axi-cel. No significant survival differences were found between liso-cel and axi-cel. Propensity score and subanalyses of patients treated in the second-line vs third-line or later settings yielded similar outcomes. Compared to axi-cel, the objective response rate at 100 days was higher for liso-cel and lower for tisa-cel. Rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hematotoxicity, and febrile neutropenia were significantly higher with axi-cel. However, no significant differences in the cumulative incidence of infections or nonrelapse mortality were found. Axi-cel was associated with faster vein-to-vein time (axi-cel, 35 days; tisa-cel, 43 days; liso-cel, 41 days) and fewer out-of-specification products (axi-cel, 2%; tisa-cel, 4%; liso-cel, 11%). These results provide insights into potential differential outcomes depending on product selection.

Blood AdvancesVol. 9(21)
Robert Wood Johnson University Hospital (US), Hackensack University Medical Center (US), Memorial Sloan Kettering Cancer Center (US), Tel Aviv University (IL), Cornell University (US), Sheba Medical Center (IL), Rambam Health Care Campus (IL), Johnson University (US), Rappaport Family Institute for Research in the Medical Sciences (IL), Academic College of Tel Aviv-Yafo (IL), Centre Hospitalier de l’Université de Montréal (CA), Hackensack Meridian Health (US), Center for Discovery (US), Hospital Universitario Ramón y Cajal (ES), Université de Montréal (CA)
Amgen, Bristol-Myers Squibb, Sanofi, Gilead Sciences, Royal College of Physicians and Surgeons of Canada, Angiocrine Bioscience, Incyte, Omeros Corporation
Openalex Percentile: Top 4%
CAR-T cell therapy research
5.23
DOIOpen Access PDFOpenAlex
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