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. 2019 Sep 12;134(11):860-866.
doi: 10.1182/blood.2019001694. Epub 2019 Jul 18.

Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma

Matthew J Frigault  1   2 , Jorg Dietrich  1   3 , Maria Martinez-Lage  4 , Mark Leick  1 , Bryan D Choi  1   5 , Zachariah DeFilipp  1   2 , Yi-Bin Chen  1   2 , Jeremy Abramson  1   6 , Jennifer Crombie  7 , Philippe Armand  7 , Lakshmi Nayak  7 , Chris Panzini  1 , Lauren S Riley  1 , Kathleen Gallagher  1 , Marcela V Maus  1   2
Affiliations

Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma

Matthew J Frigault et al. Blood. .

Abstract

Chimeric antigen receptor (CAR) T cells targeting CD19 have emerged as a leading engineered T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma. The phase 1/2 clinical trials that led to US Food and Drug Administration approval excluded patients with central nervous system (CNS) involvement, due to strict eligibility criteria. Here, we report on our institutional experience with 8 secondary CNS lymphoma patients treated with commercial tisagenlecleucel. No patient experienced greater than grade 1 neurotoxicity, and no patient required tocilizumab or steroids for CAR T-cell-mediated toxicities. Biomarker analysis suggested CAR T-cell expansion, despite the absence of systemic disease, and early response assessments demonstrated activity of IV infused CAR T cells within the CNS space.

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Conflict of interest statement

Conflict-of-interest disclosure: M.J.F. has acted as a consultant for and received honoraria from Novartis, Kite/Gilead, Nkarta Therapeutics, Xenetic Biosciences, and Arcellx. Y.-B.C. has acted as a consultant for AbbVie, Magenta Therapeutics, Equillium, Takeda, Kiadis Pharma, and Incyte. J.A. has acted as a consultant for AbbVie, Bayer, Celgene, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Juno Therapeutics, Karyopharm Therapeutics, Kite Pharma, Merck, and Novartis. P.A. has acted as a consultant for Merck, BMS, Pfizer, Affimed, Adaptive, Infinity, and ADC Therapeutics; has received institutional research funding from Merck, Bristol-Myers Squibb, Affimed, Adaptive Biotechnologies, Roche, Tensha Therapeutics, Otsuka, Sigma-Tau Pharnmaceuticals, and Genentech; and has received honoraria from Merck. L.N. has acted as a consultant for Bristol-Myers Squibb. M.V.M. has acted as a consultant for Novartis and is an inventor on unrelated patents licensed to Novartis. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Biomarker and imaging correlates of patients treated with tisagenlecleucel. (A) CRP trends of secondary CNS lymphoma patients treated with tisagenlecleucel. Red, D+30 responders; blue, D+30 nonresponders/deceased. (B) Time-matched serum and CSF (via ommaya) on days 0, 7, 14, and 28 of tisagenlecleucel infusion, as measured by Luminex assay for patient 3. Error bars, SEM. Data are technical triplicates. (C) MRI of patient 3 during inflammatory flare on D+6 with linear enhancement along the lower thoracic cord, conus, and cauda equina nerve roots (left panel, denoted by arrows) with subsequent resolution by D+180 (right panel). (D) MRI of patient 8 demonstrating resolution of the left middle cranial fossa enhancing mass lesion with decreased expansile T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the left anterior temporal white matter.
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Comment in

References

    1. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. - PMC - PubMed
    1. Schuster SJ, Bishop MR, Tam CS, et al. ; JULIET Investigators . Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45-56. - PubMed
    1. Karschnia P, Jordan JT, Forst DA, et al. Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells. Blood. 2019;133(20):2212-2221. - PubMed
    1. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome [published correction appears in Blood. 2016;128(11):1533]. Blood. 2014;124(2):188-195. - PMC - PubMed
    1. US Department of Health and Human Services Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs.... Accessed 29 July 2019.

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