Outcomes of CD19 CAR-T therapy in central nervous system lymphoma: Insights from a multicentre experience.

in British journal of haematology by Giulio Cassanello, Efrat Luttwak, Samantha Brown, Sean M Devlin, Brandon Imber, Andrew Ip, Lori A Leslie, Noa Golan Accav, Abraham Avigdor, Ronit Marcus, Ofrat Beyar-Katz, Magdalena Corona, Alejandro Luna De Abia, Jacopo Calabrese De Feo, Alfredo Rivas Delgado, Jennifer K Lue, Christian Grommes, Gunjan L Shah, Jae Park, Miguel-Angel Perales, Gilles Salles, Roni Shouval, Michael Scordo, M Lia Palomba

TLDR

  • Anti-CD19 CAR-T therapy demonstrates feasibility and safety in central nervous system lymphoma patients, with the specific CAR-T product infused emerging as a factor influencing outcomes.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has reshaped the treatment paradigm for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, its role in central nervous system lymphoma (CNSL) remains uncertain. We conducted a multicentre, retrospective study on 54 adult R/R CNSL patients treated at four international institutions with commercial (axi-cel, tisa-cel, liso-cel) or a point of care (POC) CD19-CAR T-cell products. At day 100 post CAR-T infusion, 65% of patients attained a complete response as their best response in both systemic and central nervous system compartments. The median progression-free survival (PFS) was 7.5 months, with a 1-year PFS of 35%. The median overall survival (OS) was 19 months, with a 1-year OS of 63%. In multivariable analyses, CAR-T product was significantly associated with PFS (p = 0.009) and OS (p = 0.013), with patients receiving tisa-cel exhibiting poorer outcomes than axi-cel and patients receiving liso-cel or POC CAR-T product demonstrating better outcomes than axi-cel. Toxicity profiles were consistent with pivotal trials in R/R DLBCL. Grade ≥3 cytokine release syndrome occurred in 11% of patients, while grade ≥3 immune-effector cell-associated neurotoxicity syndrome was observed in 28%. Our study supports the feasibility and safety of anti-CD19 CAR-T therapy in CNSL. The specific CAR-T product infused emerged as a factor influencing outcomes.

Overview

  • The study retrospectively analyzed 54 adult relapsed/refractory central nervous system lymphoma (CNSL) patients treated with CD19-chimeric antigen receptor (CAR) T-cell products at four international institutions.
  • The study aimed to evaluate the feasibility, safety, and efficacy of anti-CD19 CAR-T therapy in CNSL patients.
  • The primary objective was to assess the complete response rate, progression-free survival (PFS), and overall survival (OS) of CNSL patients receiving CAR-T therapy.

Comparative Analysis & Findings

  • At day 100 post-CAR-T infusion, 65% of patients achieved a complete response as their best response in both systemic and central nervous system compartments
  • The median PFS was 7.5 months, with a 1-year PFS of 35%, and median OS was 19 months, with a 1-year OS of 63%.
  • Multivariable analyses showed that CAR-T product was significantly associated with PFS and OS, with patients receiving tisa-cel exhibiting poorer outcomes than axi-cel and patients receiving liso-cel or POC CAR-T product demonstrating better outcomes than axi-cel

Implications and Future Directions

  • The study demonstrates the feasibility and safety of anti-CD19 CAR-T therapy in CNSL patients
  • The findings support the need for further investigation into the optimal CAR-T product for CNSL patients and the potential for improved outcomes with alternative products
  • Future studies should focus on identifying factors influencing outcomes and optimizing treatment regimens for CNSL patients
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