Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Feb;206(2):644-651.
doi: 10.1111/bjh.19961. Epub 2024 Dec 22.

Brexucabtagene autoleucel in-vivo expansion and BTKi refractoriness have a negative influence on progression-free survival in mantle cell lymphoma: Results from CART-SIE study

Federico Stella  1   2 , Annalisa Chiappella  2 , Martina Magni  2 , Francesca Bonifazi  3 , Chiara De Philippis  4 , Maurizio Musso  5 , Ilaria Cutini  6 , Silva Ljevar  7 , Anna Maria Barbui  8 , Mirko Farina  9 , Massimo Martino  10 , Massimo Massaia  11 , Giovanni Grillo  12 , Piera Angelillo  13 , Barbara Botto  14 , Francesca Patriarca  15 , Mauro Krampera  16 , Luca Arcaini  17   18 , Maria Chiara Tisi  19 , Pierluigi Zinzani  3 , Federica Sorà  20 , Stefania Bramanti  4 , Martina Pennisi  2 , Cristiana Carniti  2 , Paolo Corradini  1   2
Affiliations
Observational Study

Brexucabtagene autoleucel in-vivo expansion and BTKi refractoriness have a negative influence on progression-free survival in mantle cell lymphoma: Results from CART-SIE study

Federico Stella et al. Br J Haematol. 2025 Feb.

Abstract

Brexucabtagene autoleucel (brexu-cel) has revolutionized the treatment of patients affected by mantle cell lymphomas. In this prospective, observational multicentre study, we evaluated 106 patients, with longitudinal brexu-cel kinetics in peripheral blood monitored in 61 of them. Clinical outcomes and toxicities are consistent with previous real-world evidence studies. Notably, beyond established poor prognostic factors-such as blastoid variant and elevated lactate dehydrogenase-Bruton tyrosine-kinase inhibitors (BTKi) refractoriness and platelet count emerged as significant predictors of survival. Specifically, the 1-year overall survival was 56% in BTKi-refractory patients compared to 92% in BTKi-relapsed patients (p = 0.0001). Our study also demonstrated that in-vivo monitoring of brexu-cel expansion is feasible and correlates with progression-free survival and toxicities. Progression-free survival at 1 year was 74% in patients categorized as strong expanders, based on brexu-cel peak concentration, versus 54% in poor expanders (p = 0.02). Furthermore, in-vivo expansion helped identify a high-risk group of non-responders, those with progressive or stable disease at the 90-day post-infusion evaluation (OR = 4.7, 95% CI = 1.1-34, p = 0.04) characterized by dismal outcomes. When integrated with other clinical factors, monitoring brexu-cel expansion could assist in recognizing patients at high risk of early relapse.

Keywords: CAR T‐cell; brexu‐cel; in vivo expansion; mantle cell lymphoma; real world.

PubMed Disclaimer

Conflict of interest statement

Federico Stella—nothing to disclose; Annalisa Chiappella—reports other support from Gilead Sciences, Ideogen, Roche, Secura Bio, Takeda, AbbVie, Eli Lilly and Company, Incyte, Janssen‐Cilag, and Novartis outside the submitted work; Martina Magni—nothing to disclose; Francesca Bonifazi—fees from Novartis and Kite‐Gilead; Chiara De Philippis—nothing to disclose; Maurizio Musso—advisory board Kite/Gilead; Novartis; BMS. Speakers bureau: Kite/Gilead; Novartis; BMS; Ilaria Cutini—nothing to disclose, Silva Ljevar—nothing to disclose; Anna Maria Barbui—nothing to disclose; Mirko Farina—nothing to disclose; Massimo Martino—advisory board Kite/Gilead; Novartis; BMS. Speakers bureau: Kite/Gilead; Novartis; BMS; Massimo Massaia—nothing to disclose; Giovanni Grillo—nothing to disclose; Piera Angelillo—Incyte, Barbara Botto—nothing to disclose, Francesca Patriarca—Sanofi, Menarini, Novartis, BMS; Mauro Krampera—Advisory boards and honoraria for lectures/educational events: Kite Gilead, Novartis, Janssen‐Cilag, Incyte, AbbVie, BeiGene, Menarini StemLine, Roche; Luca Arcaini—Honoraria: EUSA Pharma, Novartis. Advisory boards for Roche, Janssen‐Cilag, Verastem, Incyte, EUSA Pharma, Celgene/Bristol Myers Squibb, Kite/Gilead, ADC Therapeutics, Novartis; Maria Chiara Tisi—personal fees from Novartis, Gilead, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Sobi and Incyte; Pierluigi Zinzani—Consultant: MSD, Eusapharma, Novartis; Advisory boards: ADC Therapeutics, Astrazeneca, BeiGene, BMS, Celltrion, Eusapharma, Gilead, Incyte, Janssen‐Cilag, KyowaKirin, MSD, Novartis, Roche, Sandoz, SecuraBio, Servier, Takeda; speakers bureau: Astrazeneca, Beigene, BMS, Celltrion, Eusapharma, Gilead, Incyte, Janssen‐Cilag, Kyowa‐Kirin, MSD, Novartis, Roche, Servier, Takeda; Federica Sorà—nothing to disclose; Stefania Bramanti—Speaker bureau: Bms; Gilead, Novartis, Advisory Board Novartis, Travel Accomodation Novartis, Roche, Martina Pennisi—nothing to disclose, Cristiana Carniti—nothing to disclose, Paolo Corradini—Advisory boards: AbbVie, ADC Therapeutics, Amgen, BeiGene, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda; honoraria for lectures: AbbVie, Amgen, Celgene, Gilead/Kite, Janssen, Novartis, Roche, Sanofi, Takeda.

Figures

FIGURE 1
FIGURE 1
Overall and progression‐free survival: Global (A and B) and according to BTKi refractoriness (C and D). [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
In‐vivo brexu‐cel expansion—(A) Expansion kinetics; (B) Day 90 response according to expansion; (C) ROC curve to identify a CMAX cut‐off with higher sensitivity (sens) and specificity (spec) in predicting day 90 response; (D) progression‐free survival according to the CMAX [Colour figure can be viewed at wileyonlinelibrary.com].
See this image and copyright information in PMC

References

    1. Martin P, Maddocks K, Leonard JP, Ruan J, Goy A, Wagner‐Johnston N, et al. Postibrutinib outcomes in patients with mantle cell lymphoma. Blood. 2016;127(12):1559–1563. https://ashpublications.org/blood/article/127/12/1559/35048/Postibrutini... - PubMed
    1. Cheah CY, Seymour JF, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34(11):1256–1269. 10.1200/JCO.2015.63.5904 - DOI - PubMed
    1. Jain P, Romaguera J, Srour SA, Lee HJ, Hagemeister F, Westin J, et al. Four‐year follow‐up of a single arm, phase II clinical trial of ibrutinib with rituximab (IR) in patients with relapsed/refractory mantle cell lymphoma (MCL). Br J Haematol. 2018;182(3):404–411. 10.1111/bjh.15411 - DOI - PubMed
    1. Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, et al. KTE‐X19 CAR T‐cell therapy in relapsed or refractory mantle‐cell lymphoma. N Engl J Med. 2020;382(14):1331–1342. 10.1056/NEJMoa1914347 - DOI - PMC - PubMed
    1. Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, et al. Three‐year follow‐up of KTE‐X19 in patients with relapsed/refractory mantle cell lymphoma, including high‐risk subgroups, in the ZUMA‐2 study. J Clin Oncol. 2023;41(3):555–567. 10.1200/JCO.21.02370 - DOI - PMC - PubMed

Publication types

Substances