Critical Care Management of Chimeric Antigen Receptor T Cell–related Toxicity. Be Aware and Prepared

Abstract

CAR (chimeric antigen receptor) T cells (CARTs) are genetically engineered T cells that express CARs, with impressive clinical activity in relapsed and refractory hematologic malignancies, primarily acute lymphoblastic leukemia and diffuse large B-cell lymphoma. The most frequent life-threatening adverse events after CART infusion are cytokine release syndrome and CAR-related encephalopathy syndrome, which can occur within hours or days after administration. IL-6 released by macrophages and monocytes plays a major role in the pathogenesis of cytokine release syndrome and CAR-related encephalopathy syndrome, and IL-6 blockade and steroids contribute to fast resolution of symptoms. Critical care management plays an important role in patients receiving CARTs, as up to half of patients might need an admission to the ICU and lifesaving interventions. As new treatment indications and CART constructs enter the clinic, the number of patients requiring ICU admission will rapidly increase, with profound consequences for the use of ICU resources, training requirements, clinical expertise, multidisciplinary collaboration, and hospital organization. Research is also needed to validate at large scale biomarkers that allow doctors to risk-stratify patients for both their risk to develop severe toxicity and their likelihood to respond to therapy.