TY - JOUR
T1 - Outcomes of CD19 CAR-T therapy in central nervous system lymphoma
T2 - Insights from a multicentre experience
AU - Cassanello, Giulio
AU - Luttwak, Efrat
AU - Brown, Samantha
AU - Devlin, Sean M.
AU - Imber, Brandon
AU - Ip, Andrew
AU - Leslie, Lori A.
AU - Accav, Noa Golan
AU - Avigdor, Abraham
AU - Marcus, Ronit
AU - Beyar-Katz, Ofrat
AU - Corona, Magdalena
AU - Luna De Abia, Alejandro
AU - Calabrese De Feo, Jacopo
AU - Rivas Delgado, Alfredo
AU - Lue, Jennifer K.
AU - Grommes, Christian
AU - Shah, Gunjan L.
AU - Park, Jae
AU - Perales, Miguel Angel
AU - Salles, Gilles
AU - Shouval, Roni
AU - Scordo, Michael
AU - Palomba, M. Lia
N1 - Publisher Copyright:
© 2025 British Society for Haematology and John Wiley & Sons Ltd.
PY - 2025/8
Y1 - 2025/8
N2 - 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.
AB - 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.
KW - cellular therapies
KW - haematological oncology
KW - immunotherapy
KW - lymphoma
UR - https://www.scopus.com/pages/publications/105009485105
U2 - 10.1111/bjh.20234
DO - 10.1111/bjh.20234
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C2 - 40589238
AN - SCOPUS:105009485105
SN - 0007-1048
VL - 207
SP - 525
EP - 534
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 2
ER -