1. Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China 2. Nanjing Legend Biotech Inc., Nanjing 210000, China
Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5–10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
Symptoms, e.g., fever, nausea, fatigue, headache, myalgia, and malaise, requiring only symptomatic management
II
Symptoms responding to moderate intervention, including oxygen requirement<40%, grade 2 organ toxicity, or hypotension responding to IV fluids or low doses of one vasopressor (e.g.,<20 mg/min of norepinephrine)
III
Oxygen requirement>40%, hypotension requiring high-dose or multiple vasopressors, grade 4 transaminitis, and grade 3 organ toxicity at other sites
IV
Life-threatening symptoms requiring ventilator support or grade 4 organ toxicity other than transaminitis
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