Introduction: The prognosis of patients (pts) with relapsed or refractory (r/r) large B cell lymphoma (LBCL) and central nervous system (CNS) involvement is dismal. Standard treatment for pts with r/r LBCL are anti-CD19 chimeric antigen receptor T-cells (CART). Several reports with limited numbers of patients suggest that CART might also be an effective treatment for pts with CNS lymphoma. This EBMT registry study aimed at compiling data to investigate the potential of CART in pts with primary (PCNSL) or secondary CNS lymphoma (SCNCL).

Methods: Centers contributing to the EBMT database were asked for cases of PCNSL and SCNSL, treated with CART between 01/ 2018 and 07/ 2022. Reported pts were identified in the database, patient characteristics and pre-treatment retrieved, and major clinical endpoints analyzed. To calculate overall survival (OS) and progression-free survival (PFS) from date of CART infusion Kaplan Meier estimates were used, whereas cumulative incidence was used for relapse incidence (RI) and non-relapse mortality (NRM).

Results: 88 pts with PCNSL (n=10) or SCNSL (n=78) with complete information on major endpoints were analyzed. Median follow-up was 20.3 months [95% CI: 16-27]. Median age was 63 years (range 31-80), 52 pts (59%) were male. ECOG was ≥ 2 in 19 of 86 pts (22%). 41 of 65 pts (63%) had undergone ≥3 prior treatment lines, 56 of 82 pts (68%) were refractory to at least one previous line of chemotherapy. 29 of 86 pts (34%) had received autologous stem-cell transplantation (ASCT). Of 84 patients 68% were not in remission at time of CART, 8% were in complete remission (CR) and 24% in partial remission (PR). Information on disease status was missing for four patients. 49 pts were treated with axicabtagene ciloleucel, 39 pts received tisagenlecleucel. OS- and PFS-rates at 24 months were 47% [95% CI: 37-61] and 32% [CI: 23-45] for the whole cohort (figure 1). RI at 24 months was 58% [CI: 47-68], NRM 10% [CI: 4-19]. OS and PFS for pts in CR/PR were 58% [CI 40-85] and 51% [CI: 33-77]. For 57 pts not in remission at CART infusion OS and PFS were 42% [CI: 30-59] and 24% [CI: 14-39], respectively.

Conclusion: With a 47% OS rate at 24 months CART seem to be a very effective therapeutic option in heavily pre-treated r/r LBCL with CNS manifestation. These results compare favorably with those reported for conventional treatment including pts treated with ASCT. Indeed, these results are similar to those reported by real-world analyses of CART in LBCL without CNS manifestation (Bethge et al., 2021, Le Gouill et al., 2021). Based on these promising early results, we consider treatment with CART for pts with CNS involvement and r/r LBCL as the preferred treatment option.

Fuhrmann:BMS: Honoraria. Novak:BMS: Other: Advisory Board; Novartis: Other: Advisory Boards; Gilead: Other: Advisory Boards. Beauvais:BMS: Honoraria, Other: Advisory Board; Kite/Gilead: Honoraria, Other: Advisory Board. Vandenberghe:Celgene/BMS: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Other: Travel support; Janssen Biotech: Consultancy, Research Funding; Miltenyi Biotec: Consultancy; Gilead Sciences: Consultancy, Other: Travel Support; Pfizer: Research Funding. Kröger:Takeda: Consultancy; Sanofi: Honoraria; Kite: Honoraria; Neovii: Honoraria; BMS: Honoraria; Novartis: Honoraria, Research Funding; Jazz: Honoraria; Riemser: Research Funding; DKMS: Research Funding; Amgen: Research Funding; BMS: Research Funding. Ram:BMS, Takeda, Sanofi, Pfizer: Honoraria; Novartis: Honoraria, Research Funding; Gilead: Honoraria; MSD: Honoraria. Finke:Gilead Sciences: Current holder of stock options in a privately-held company; AbbVie: Current holder of stock options in a privately-held company; Roche: Current holder of stock options in a privately-held company; Riemser: Honoraria, Research Funding, Speakers Bureau; Neovii: Honoraria, Research Funding, Speakers Bureau; Medac: Honoraria, Research Funding. Wulf:Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. von Bonin:BMS: Other: Advisory Board; Novartis: Other: Advisory Board; Janssen: Research Funding; Kite: Other: Advisory Board. Bug:BMS: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Jazz: Honoraria, Research Funding. Kuhnl:Kite Gilead: Honoraria; BMS: Honoraria; Abbvie: Honoraria; Novartis: Honoraria, Research Funding. Stoelzel:Medscape: Consultancy, Honoraria, Other: travel support; medac GmbH: Consultancy, Honoraria, Other: travel support. von Tresckow:Gilead Kite: Consultancy, Other: Travel Support; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel Support, Research Funding; IQVIA: Consultancy; Miltenyi: Consultancy; Allogene: Consultancy; BMS/Celgene: Consultancy, Honoraria; Cerus: Consultancy; Roche: Consultancy, Honoraria, Other: Travel Support; Noscendo: Consultancy; Pentixapharm: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel Support, Research Funding; MSD: Consultancy, Honoraria, Other: Travel Support, Research Funding; AbbVie: Other: Travel Support; AstraZeneca: Honoraria, Other: Travel Support; Lilly: Consultancy, Honoraria, Other: Travel Support; Pierre Fabre: Other: Travel support. Sureda Balari:Astra Zeneca: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; MSD: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria; Jannsen: Consultancy, Honoraria; Pierre Fabre: Consultancy, Honoraria; GenMab: Consultancy, Honoraria; Kite: Consultancy, Honoraria. Dreger:AbbVie: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Honoraria; bluebird bio: Consultancy; Novartis: Consultancy, Honoraria; Miltenyi: Consultancy; Riemser: Honoraria; MD Kompetenz-Centrum Onkologie: Honoraria. Schmitz:BMS: Current holder of stock options in a privately-held company; Miltenyi: Other: Travel Support; Roche: Research Funding; Allogene: Honoraria, Other: Travel Support; Jansen: Research Funding; Astra Zeneca: Research Funding. Glass:Roche: Consultancy, Honoraria, Research Funding; Gilead/Kite: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Miltenyi: Consultancy, Honoraria; Lonca: Consultancy; Jazz: Consultancy.

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2023
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