Toxicities of CAR T-Cell Therapy and the Role of the Consultation-Liaison Psychiatrist

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapy is a promising novel T-cell immunotherapy in cancer treatment that has shown clinical efficacy in treating refractory CD19+ B-cell malignancies. However, its use is associated with severe immune-mediated toxicities, including cytokine release syndrome (CRS) and CAR T-cell-related encephalopathy syndrome (CRES). CRS is a systemic inflammatory immune response resulting in symptoms ranging from constitutional to profound organ dysfunction; CRES is a neurotoxicity that can occur concurrently or separately from CRS. Objective This case report and discussion provide an overview of CRES and CRS and highlight special considerations for consultation-liaison (CL) psychiatrists. Method We describe a case of a woman treated with CAR T-cell therapy who developed CRES and CRS, including neuropsychiatric manifestations. We reviewed the literature using “Pubmed” search terms of “CAR T-cell therapy” and “CRS” or “CRES”. Discussion We provide an overview of CRS and CRES. We also highlight special considerations for the CL psychiatrist including completing a delirium workup, weighing risks/benefits of psychotropic agents to treat neuropsychiatric manifestations of CRES, and recognizing the potential for long-term behavioral health symptoms related to CRES, CRS, or their treatments. Conclusion CAR T-cell immunotherapy is becoming more prevalent. It is imperative that CL psychiatrists become familiar with this immunotherapy's toxicities including pathophysiology, neuropsychiatric manifestations, and evaluation and management to ensure optimal patient care. Finally, since immune activation, inflammation, and cytokine activation - as occurs with CRES - are known to affect cognitive and/or emotional functioning, CL psychiatrists must remain vigilant for these potential long-term psychiatric complications.