How I treat refractory CRS and ICANS after CAR T-cell therapy

Michael D Jain, Melody Smith, Nirali N Shah, Michael D Jain, Melody Smith, Nirali N Shah

Abstract

The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly because of the expanding indications for standard-of-care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), alongside the steady use of both tocilizumab and corticosteroids for treatment, have been essential in facilitating the widespread use. Preemptive interventions to prevent more severe toxicities have improved safety, facilitating CAR T-cell therapy in medically frail populations and in those at high risk of severe CRS/ICANS. Nonetheless, the development of persistent or progressive CRS and ICANS remains problematic because it impairs patient outcomes and is challenging to treat. In this case-based discussion, we highlight a series of cases of CRS and/or ICANS refractory to front-line interventions. We discuss our approach to managing refractory toxicities that persist or progress beyond initial tocilizumab or corticosteroid administration, delineate risk factors for severe toxicities, highlight the emerging use of anakinra, and review mitigation strategies and supportive care measures to improve outcomes in patients who develop these refractory toxicities.

Conflict of interest statement

Conflict-of-interest disclosure: M.D.J. declares a consultancy/advisory role for Kite/Gilead, BMS, Novartis, and MyeloidTx and research funding from Kite/Gilead and Incyte. N.N.S. receives royalties from CARGO Therapeutics and has participated in advisory boards for Sobi and VOR. M.S. declares a consultancy/advisory role for BMS.

© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Approach to mitigate severe CRS/ICANS and progressive toxicities despite the optimal use of first-line therapies.

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