Outcomes of <scp>CD19 CAR</scp>‐T therapy in central nervous system lymphoma: Insights from a multicentre experience
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.
Authors
- Efrat Luttwak (ORCID: https://orcid.org/0000-0003-0212-2135)
- Lori Ann Leslie (ORCID: https://orcid.org/0000-0002-7265-4076)
- Samantha Brown (ORCID: https://orcid.org/0000-0001-5352-974X)
- Christian Grommes
- Ronit Marcus
- Gunjan L. Shah (ORCID: https://orcid.org/0000-0002-9977-0456)
- Brandon S. Imber (ORCID: https://orcid.org/0000-0002-1281-5915)
- Andrew Ip (ORCID: https://orcid.org/0000-0003-0456-5618)
- Magdalena Corona (ORCID: https://orcid.org/0000-0002-6553-0171)
- Jennifer Kimberly Lue (ORCID: https://orcid.org/0000-0001-8153-1820)
- Giulio Cassanello (ORCID: https://orcid.org/0000-0002-2192-9930)
- Roni Shouval (ORCID: https://orcid.org/0000-0001-9827-8032)
- Ofrat Beyar‐Katz (ORCID: https://orcid.org/0000-0002-5631-4776)
- Michael Scordo (ORCID: https://orcid.org/0000-0002-9484-0240)
- Alfredo Rivas‐Delgado (ORCID: https://orcid.org/0000-0003-0385-3415)
- M. Lia Palomba
- Alejandro Luna (ORCID: https://orcid.org/0000-0003-2201-3091)
- Miguel‐Angel Perales (ORCID: https://orcid.org/0000-0002-5910-4571)
- Gilles Salles (ORCID: https://orcid.org/0000-0002-9541-8666)
- Jae H. Park (ORCID: https://orcid.org/0000-0002-2903-5130)
- Abraham Avigdor
- Sean Devlin
- Noa Golan Accav
- Jacopo Calabrese De Feo
Institutions
- Hackensack University Medical Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Humanitas University (IT)
- Tel Aviv University (IL)
- University of Milan (IT)
- Cornell University (US)
- Sheba Medical Center (IL)
- Rambam Health Care Campus (IL)
- Hospital Universitario 12 De Octubre (ES)
- Rappaport Family Institute for Research in the Medical Sciences (IL)
- Hospital Universitario Ramón y Cajal (ES)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1111/bjh.20234
- Citations
- 3
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 3.14