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Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL

Bone Marrow Transplantation volume 56, pages 552–566 (2021)Cite this article

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Abstract

Treatment with CD19 or CD22-targeted chimeric antigen receptor-engineered T (CD19/CD22 CAR-T) cells achieve complete responses in 60–90% of adults and children with refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL). This led to the approval of tisagenlecleucel (Kymriah) by the FDA and several European regulatory agencies in ALL patients up to 25 years of age. Although CAR T-cell therapy is likely to transform the ALL therapeutic landscape, its development and wide dissemination have been impacted by the occurrence of significant toxicities; namely, cytokine release syndrome (CRS) and Immune effector cell-Associated Neurotoxicity Syndrome (ICANS) have been reported at higher rates in ALL patients compared to other B cell malignancies, particularly in the adult population. Here, we review recent data suggesting a significant proportion of ALL patients are at risk of developing severe, sometimes life-threatening, CRS, and ICANS after CD19 and CD22 CAR T-cell therapy. After describing the key clinical and laboratory features of severe CRS and ICANS, we explore the disease and treatment-related factors that may predict the severity of these toxicities. Last, we review strategies under investigation in the prophylactic and therapeutic settings to improve the safety of CAR T-cells for ALL.

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Fig. 1: Incidences of severe CRS and ICANS after CD19 CAR T-cell therapy for ALL.
Fig. 2: Prediction of dose-outcomes relationships after CD19 CAR T cell therapy (adapted from Hay et al, Blood 2017).

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Acknowledgements

J.G. acknowledges the FHCRC/UW Cancer Consortium Cancer Center Support Grant Clinical Scholar Support (NCI / P30 CA015704).

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  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Vipul S Sheth MD & Jordan Gauthier

  2. Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Jordan Gauthier

  3. Division of Medical Oncology, University of Washington, Seattle, WA, USA

    Jordan Gauthier

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Sheth, V.S., Gauthier, J. Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL. Bone Marrow Transplant 56, 552–566 (2021). https://doi.org/10.1038/s41409-020-01134-4

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