Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Rawan FaramandMarco L Davila

Abstract

One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel). Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression. We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity. These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strateg...Continue Reading

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Citations

Jan 20, 2021·The Journal of Clinical Investigation·Emiliano RoselliMarco L Davila
Feb 9, 2021·Expert Opinion on Biological Therapy·Christina A BachmeierMarco L Davila
Oct 27, 2020·Frontiers in Immunology·Eleonora PonterioTobias Longin Haas
Mar 2, 2021·Frontiers in Immunology·Lorenzo LindoKevin Anthony Hay
May 14, 2021·Blood·Paolo Strati, Sattva S Neelapu
Jun 17, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Matthew J FrankDavid B Miklos
Sep 1, 2021·Expert Opinion on Biological Therapy·Massimo MartinoBenedetto Bruno
Sep 2, 2021·Journal of Blood Medicine·Omar Castaneda-Puglianini, Julio C Chavez

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