Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline

Abstract

PURPOSE To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric antigen receptor (CAR) T-cell therapy. METHODS A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021. RESULTS The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell–related toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell–associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell–associated neurotoxicity syndrome should be managed with corticosteroids and supportive care. Additional information is available at www.asco.org/supportive-care-guidelines .

Cytokine Release Syndrome and Immune-Related Pneumonitis Associated With Tumor Progression in a Pulmonary Pleomorphic Carcinoma Treated With Nivolumab Plus Ipilimumab Treatment: A Case Report

“…CRS has been reported to occur relatively early after immunotherapy. 1 , 7 Nevertheless, the onset of CRS in the present case was delayed possibly owing to its association with tumor growth. The use of G-CSF receptor blocker 8 for G-CSF–producing tumors may reduce the risk of irAE development in patients with the tumors.…”

“…CRS is recommended to be primarily managed with tocilizumab. 1 The symptoms associated with CRS in this case were nausea, severe hypotension, and respiratory failure. 1 , 7 Although the blood pressure immediately responded to steroid pulse therapy, the infiltrative shadow in the lung field did not improve, and tocilizumab was administered considering CRS.…”

“… 1 The symptoms associated with CRS in this case were nausea, severe hypotension, and respiratory failure. 1 , 7 Although the blood pressure immediately responded to steroid pulse therapy, the infiltrative shadow in the lung field did not improve, and tocilizumab was administered considering CRS. Within 2 days, expansion of the pulmonary infiltrative shadow and deterioration of oxygenation were observed ( Supplementary Fig.…”

“…CRS occurs either in the hyperacute phase, minutes to hours after the administration of these drugs, or in some days to 2 weeks after the proliferation of the administered T-cells. 1 Here, we present a case of a patient with pulmonary pleomorphic carcinoma treated with nivolumab plus ipilimumab who developed CRS with tumor progression. Tocilizumab, an antihuman interleukin (IL)-6 monoclonal antibody, was effective in controlling CRS, whereas infliximab, an antihuman tumor necrosis factor α monoclonal antibody, was necessary for controlling complicated pneumonitis.…”

Cancer-Homing CAR-T Cells and Endogenous Immune Population Dynamics

“…This frequently leads to multiorgan dysfunction, pulmonary failure, and death [ 59 ]. Consequent therapeutic intervention requires the intense management of treated patients [ 60 , 61 ].…”