Fatal late-onset CAR T-cell-mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma

• Verfasst von: Jung, Susanne Claudia [VerfasserIn]
• Verfasst von: Greiner, Jochen [VerfasserIn]
• Verfasst von: Harsdorf, Stephanie von [VerfasserIn]
• Verfasst von: Popović, Pavle [VerfasserIn]
• Verfasst von: Moll, Roland [VerfasserIn]
• Verfasst von: Schittenhelm, Jens Florian [VerfasserIn]
• Verfasst von: Kandilaris, Kosmas [VerfasserIn]
• Verfasst von: Daniel, Volker [VerfasserIn]
• Verfasst von: Kunz, Alexander [VerfasserIn]
• Verfasst von: Schmitt, Michael [VerfasserIn]
• Verfasst von: Dreger, Peter [VerfasserIn]
• Titel: Fatal late-onset CAR T-cell-mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma
• Verf.angabe: Susanne Jung, Jochen Greiner, Stephanie von Harsdorf, Pavle Popovic, Roland Moll, Jens Schittenhelm, Kosmas Kandilaris, Volker Daniel, Alexander Kunz, Michael Schmitt, and Peter Dreger
• E-Jahr: 2021
• Jahr: October 4, 2021
• Umfang: 5 S.
• Fussnoten: Gesehen am 15.12.2021
• Titel Quelle: Enthalten in: Blood advances
• Ort Quelle: Washington, DC : American Society of Hematology, 2016
• Jahr Quelle: 2021
• Band/Heft Quelle: 5(2021), 19, Seite 3789-3793
• ISSN Quelle: 2473-9537
• DOI: doi:10.1182/bloodadvances.2021004889
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1782237739

Abstract

Treatment with CD19-directed (CAR) T cells has evolved as a standard of care for multiply relapsed or refractory large B-cell lymphoma (r/r LBCL). A common side effect of this treatment is the immune effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can occur in up to 30% to 40% of patients treated with axicabtagene-ciloleucel (axi-cel), usually within the first 4 weeks after administration of the dose and usually responding well to steroids. We describe a case of progressive central neurotoxicity occurring 9 months after axi-cel infusion in a patient with r/r LBCL who had undergone a prior allogeneic hematopoietic cell transplant. Despite extensive systemic and intrathecal immunosuppression, neurological deterioration was inexorable and eventually fatal within 5 months. High CAR T-cell DNA copy numbers and elevated levels of interleukin-1 (IL-1) and IL-6 were found in the cerebral spinal fluid as clinical symptoms emerged, and CAR T-cell brain infiltration was observed on autopsy, suggesting that CAR T cells played a major pathogenetic role. This case of unexpected, devastating, late neurotoxicity warrants intensified investigation of neurological off-target effects of CD19-directed CAR T cells and highlights the need for continuous monitoring for late toxicities in this vulnerable patient population.