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

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.

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Publication Details

Journal
British Journal of Haematology
Published
2024-12-22
DOI
https://doi.org/10.1111/bjh.19961
Citations
7
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
2.97

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article

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

Martina Pennisi, Anna Maria Barbui, Ilaria Cutini, Massimo Massaia et al.
7 citations
British Journal of Haematology
Lymphoma Diagnosis and Treatment
2.97
article

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

Martina Pennisi, Anna Maria Barbui, Ilaria Cutini, Massimo Massaia, Fabrizio Patriarca, Luca Arcaini, Silva Ljevar, Mauro Krampera, Piera Angelillo, Maria Chiara Tisi, Giovanni Grillo, Massimo Martino, Mirko Farina, Chiara De Philippis, Martina Magni, Federica Sorà, Stéfania Bramanti, Paolo Corradini, Annalisa Chiappella, Barbara Botto, Francesca Bonifazi, Federico Stella, Cristiana Carniti, Pier Luigi Zinzani, Maurizio Musso
article en
7 citations

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.

British Journal of HaematologyVol. 206(2)
Università Cattolica del Sacro Cuore (IT), University of Verona (IT), University of Milan (IT), University of Pavia (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Azienda ospedaliera "Bianchi-Melacrino-Morelli" (IT), Azienda Unità Sanitaria Locale di Ferrara (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale Papa Giovanni XXIII (IT), Istituto di Ematologia di Bologna (IT), IRCCS Ospedale San Raffaele (IT), Policlinico San Matteo Fondazione (IT), Ospedale San Bortolo (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), IRCCS Humanitas Research Hospital (IT), La Maddalena (IT), University of Turin (IT), University of Brescia (IT)
Eli Lilly and Company, Gilead Sciences, Incyte, Ministero della Salute, Associazione Italiana per la Ricerca sul Cancro, Associazione Italiana Contro le Leucemie - Linfomi e Mieloma, Associazione Italiana Contro le Leucemie-Linfomi e Mieloma, Cilag
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Openalex Percentile: Top 8%
Lymphoma Diagnosis and Treatment
2.97
DOIOpen Access PDFOpenAlex
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