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Chimeric antigen receptors (CARs) are recombinant receptors for antigens that redirect the specificity and function of T lymphocytes or other immune cells in a single molecule. The concept of using CARs in cancer immunotherapy is that CARs, which are programmed to target tumor-associated antigens, can be replicated rapidly and homogeneously. Direct infusion of these armed tumor-targeting T cells bypasses the barriers and kinetics of active immunization. This activity describes the indications, contraindications, and complications of CART treatment and highlights the interprofessional team's role in managing cancer patients. Objectives: Identify the indications for CART therapy. Determine the complications of CART therapy. Assess the contraindications of CART therapy. Communicate some interprofessional team strategies for improving care coordination in patients who receive CART therapy. Access free multiple choice questions on this topic.

Chimeric antigen receptors (CARs) are recombinant receptors for antigens that redirect the specificity and function of T lymphocytes or other immune cells in a single molecule. The concept of using CARs in cancer immunotherapy is that CARs, which are programmed to target tumor-associated antigens, can be replicated rapidly and homogeneously. Direct infusion of these armed tumor-targeting T-cells bypass the barriers and kinetics of active immunization. Unlike general passive immunization using a direct antibody, CAR-modified T-cells with supraphysiologic activities work as an active medication, interacting with tumor-associated antigens, which results in both immediate and long-term effects of anti-neoplasm.[1][2]

Multiple side effects are associated with CAR T-cell therapy. The most common 2 are cytokine-release syndrome(CRS) and neurologic toxicities, also known as CAR-related encephalopathy syndrome (CRES). Cytokine-release syndrome is the most common adverse effect of CAR T-cell therapy. It presents with high fever, low blood pressure, and hypoxia, with or without multi-organ toxicities, including cardiovascular, gastrointestinal, respiratory, renal, hematological, and nervous system. The trigger for this condition is the activation of T-cells on the engagement of their T-cell receptors or CARs with cognate antigens expressed by the tumor cell. It typically occurs within the first week after CAR T-cell therapy and generally peaks within 1 to 2 weeks of cell administration. The management of cytokine-release syndrome is based on the grade, including temperature, systolic blood pressure, oxygen saturation, and possible toxicity to other organs. The primary points for management include supportive care (ie, acetaminophen and hypothermia blanket for fever; intravenous fluid for dehydration or hypotension; supplemental oxygen for hypoxia), corticosteroids, and Interleukin-6 antagonists. CAR-related encephalopathy syndrome is characterized by typical manifestations similar to toxic encephalopathy with early signs of diminished attention, language disturbance, and impaired handwriting. Other symptoms and signs include confusion, disorientation, agitation, aphasia, somnolence, and tremors. The pathogenesis of CRES is unclear for now. It typically happens within the first 5 days after administration. The management of CRES is also based on the grade of the components of the neurological assessment score by CARTOX-10 (CAR-T-cell-therapy-associated toxicity 10-point neurological assessment), intracranial pressure, and the presence of seizure or motor weakness. The management of CRES is similar to CRS, which primarily involves supportive care, corticosteroids, and Interleukin-6 antagonists. To minimize the risk of aspiration and increase cerebral venous flow, the head of the patient’s bed should be elevated. Neurology consultation and evaluation are also warranted.[9] Other reported adverse effects are summarized below based on the system.[10] Constitutional: Fever, rigor, malaise, fatigue, anorexia, arthralgia.

CAR-related encephalopathy syndrome is characterized by typical manifestations similar to toxic encephalopathy with early signs of diminished attention, language disturbance, and impaired handwriting. Other symptoms and signs include confusion, disorientation, agitation, aphasia, somnolence, and tremors. The pathogenesis of CRES is unclear for now. It typically happens within the first 5 days after administration. The management of CRES is also based on the grade of the components of the neurological assessment score by CARTOX-10 (CAR-T-cell-therapy-associated toxicity 10-point neurological assessment), intracranial pressure, and the presence of seizure or motor weakness. The management of CRES is similar to CRS, which primarily involves supportive care, corticosteroids, and Interleukin-6 antagonists. To minimize the risk of aspiration and increase cerebral venous flow, the head of the patient’s bed should be elevated. Neurology consultation and evaluation are also warranted.[9] Other reported adverse effects are summarized below based on the system.[10] Constitutional: Fever, rigor, malaise, fatigue, anorexia, arthralgia. Neurological: Headache, change in the level of consciousness, delirium, aphasia, apraxia, ataxia, hallucination, tremor, dysmetria, myoclonus, facial nerve palsy, seizure. Hepatic: Transaminitis, hyperbilirubinemia. Hematologic: Anemia, thrombocytopenia, neutropenia, febrile neutropenia, lymphocytopenia, B-cell aplasia, prolonged prothrombin time, prolonged activated partial thromboplastin time, elevated d-dimer, hypofibrinogenemia, disseminated intravascular coagulation, hemophagocytic lymphohistiocytosis. Cardiovascular: Tachycardia, widened pulse pressure, hypotension, arrhythmia, decreased left ventricular ejection fraction, troponinemia, QT prolongation. Pulmonary: Tachypnea, hypoxia. Renal: Acute kidney injury, hyponatremia, hypokalemia, hypophosphatemia, tumor lysis syndrome. Gastrointestinal: Nausea, emesis, diarrhea. Musculoskeletal: Myalgia, elevated creatine kinase, weakness.

Providing CAR T-cell treatment to the patient requires an interprofessional team of healthcare professionals, including physicians in different specialties, nurses, pharmacists, and laboratory technologists. CAR T-cell therapy preparation is from the patient's peripheral blood cells obtained via leukapheresis and infused into the patient for tumor attack. Clinicians are required to perform both leukapheresis and infusion. Different specialty clinicians may also be required; for example, in some facilities, the dialysis clinician performs leukapheresis, and an oncology clinician delivers immunotherapy. The clinician's significant role is to care for the patient, especially during and after the transfusion. Close attention is required to monitor adverse effects, including early symptoms and signs of cytokine-releasing syndrome and CAR-T-cell-related encephalopathy. Various physicians in different specialties are required, especially when adverse effects occur. Pharmacists are important before treatment because Interleukin-6 antagonists (ie, tocilizumab or siltuximab), corticosteroids, and emergent equipment are needed before infusion and during the recovery period in case of side effects. Critical care may also warranted if side effects are severe and need to stand by during and after the medication infusion. Neurology consultation and evaluation are required if neurotoxicity occurs. The adverse effect can happen in most organs or systems, interprofessional communication and opinion exchange are essential when taking care of a patient undergoing CAR-T cell therapy especially in the situation of any adverse effect.