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.

in British journal of haematology by Federico Stella, Annalisa Chiappella, Martina Magni, Francesca Bonifazi, Chiara De Philippis, Maurizio Musso, Ilaria Cutini, Silva Ljevar, Anna Maria Barbui, Mirko Farina, Massimo Martino, Massimo Massaia, Giovanni Grillo, Piera Angelillo, Barbara Botto, Francesca Patriarca, Mauro Krampera, Luca Arcaini, Maria Chiara Tisi, Pierluigi Zinzani, Federica Sorà, Stefania Bramanti, Martina Pennisi, Cristiana Carniti, Paolo Corradini

TLDR

  • The study evaluated the clinical outcomes and predictors of survival in patients with mantle cell lymphomas treated with brexucabtagene autoleucel (brexu-cel) and found that monitoring the treatment's expansion could help identify patients at high risk of early relapse.
  • The study's findings suggest that BTKi refractoriness, platelet count, and brexu-cel expansion monitoring could be useful tools in predicting patient outcomes and informing treatment decisions.

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.

Overview

  • The study evaluated 106 patients with mantle cell lymphomas treated with brexucabtagene autoleucel (brexu-cel) and investigated its clinical outcomes, toxicities, and predictors of survival.
  • The study aimed to assess the feasibility of in-vivo monitoring of brexu-cel expansion and its correlation with clinical outcomes and toxicities.
  • The primary objective of the study was to identify predictors of survival, including established poor prognostic factors and newly emerged predictors.

Comparative Analysis & Findings

  • The study found that BTKi refractoriness and platelet count were significant predictors of survival, with a 1-year overall survival rate of 56% in BTKi-refractory patients compared to 92% in BTKi-relapsed patients.
  • In-vivo monitoring of brexu-cel expansion correlated with progression-free survival and toxicities, with strong expanders having a 1-year progression-free survival rate of 74% compared to 54% in poor expanders.
  • The study identified a high-risk group of non-responders characterized by progressive or stable disease at the 90-day post-infusion evaluation, which had dismal outcomes (OR = 4.7, 95% CI = 1.1-34, p = 0.04).

Implications and Future Directions

  • The study's findings suggest that monitoring brexu-cel expansion could help identify patients at high risk of early relapse, allowing for early intervention and personalized treatment.
  • Further research is needed to validate the results and explore the use of brexu-cel expansion monitoring as a predictive marker for treatment response and survival.
  • The study's findings could inform the development of new treatment strategies for mantle cell lymphomas, including the use of combination therapies and personalized treatment approaches.
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