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Axicabtagene Ciloleucel CAR T-cell therapy for relapsed/refractory secondary CNS non-Hodgkin lymphoma: comparable outcomes and toxicities, but shorter remissions may warrant alternative consolidative strategies?

Bone Marrow Transplantation volume 56, pages 974–977 (2021)Cite this article

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CAR T-cell therapy has changed the treatment landscape for patients with relapsed/refractory (R/R) B-cell non-Hodgkin’s lymphoma (NHL). The FDA approvals for axicabtagene and tisagenlecleucel in NHL were based on two phase 2 clinical trials, ZUMA-1 and JULIET, that resulted in overall response rates (ORR) of 82% with axicabtagene [1] and 52% with tisagenlecleucel [2], respectively, in heavily pre-treated populations. Due to concerns that CNS involvement may increase risk and/or severity of CAR-T-related neurotoxicity, the trials excluded patients with secondary CNS lymphoma. With this selected population, neurotoxicity was observed in 67% with axicabtagene and 39% with tisagenlecleucel [2, 3]. Limited data suggests CAR-T is feasible and does not result in excess toxicity in patients with active secondary CNS lymphoma, including single-institution experience of 8 patients who received tisagenlecleucel and a study from the US Lymphoma CAR-T consortium that reported on 5 patients that received axicabtagene [4, 5]. There remains a paucity of data regarding efficacy and toxicity profile of CAR-T, particularly for use of axicabtagene, in patients with R/R B-cell NHL with secondary CNS involvement.

We report the institutional experience at UCLA Medical Center from 5 patients treated with axicabtagene between October 2017 and January 2020 for R/R NHL with secondary CNS involvement. The UCLA IRB approved this clinical study, and all patients provided written informed consent for CAR-T. Patients’ characteristics, toxicities and responses to CAR-T are shown in Table 1.

Table 1 Comprehensive table including patient characteristics, CAR-T related clinical course, and clinical responses to CAR-T therapy.
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Authors and Affiliations

  1. Department of Hematology Oncology, UCLA Medical Center, 757 Westwood Plaza, Los Angeles, CA, 90095, USA

    Sanaz Ghafouri

  2. UCLA Lymphoma Program, Division of Hematology & Oncology, Department of Medicine, UCLA Medical Center, 757 Westwood Plaza, Los Angeles, CA, 90095, USA

    John Timmerman

  3. Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, UCLA Medical Center, 757 Westwood Plaza, Los Angeles, CA, 90095, USA

    Sarah Larson

  4. Department of Hematology Oncology, UCLA Medical Center, 757 Westwood Plaza, Los Angeles, CA, 90095, USA

    Monica D. Mead

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  1. Sanaz Ghafouri
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Correspondence to Sanaz Ghafouri.

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SG and MM have no conflict of interest. JT received research funding form BMS, Kite, ImmunGene. SL is consultant for BMS.

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Ghafouri, S., Timmerman, J., Larson, S. et al. Axicabtagene Ciloleucel CAR T-cell therapy for relapsed/refractory secondary CNS non-Hodgkin lymphoma: comparable outcomes and toxicities, but shorter remissions may warrant alternative consolidative strategies?. Bone Marrow Transplant 56, 974–977 (2021). https://doi.org/10.1038/s41409-020-01099-4

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