Critical Care Medicine-Infections and Immunologic Disease>>>>>Immune Suppression: Congenital, Acquired, Drugs
Question 5#

A 62-year-old man with refractory non-Hodgkin lymphoma is admitted to hospital for infusion of chimeric antigen receptor T cells (CAR T). On day 3 following the infusion of CAR T cells, he becomes febrile to 38.9°C, hypotensive, and somnolent. Neurological examination is nonfocal. His blood pressure remains 75/40 mm Hg despite quick administration of 2 L lactated Ringer’s, and he is transferred to the ICU for further management. The infusion of norepinephrine is initiated. He now requires 6 L/min O2 via nasal cannula to maintain oxygen saturation >90%.

Which of the following is the next BEST step in management?

A. Administration of tocilizumab while ruling out infection
B. Immediate administration of empiric vancomycin and cefepime
C. Fluid and vasopressor management to support hemodynamics while cytokine release syndrome resolves
D. IV hydrocortisone

Correct Answer is B


Correct Answer: B

This patient most likely has cytokine release syndrome or sepsis, which are difficult to distinguish clinically. 

Cytokine release syndrome (CRS) is a known complication of CAR T cell therapy. This syndrome is a result of the release of proinflammatory cytokines (interleukins 6 and 10 and interferon gamma) during the interaction between genetically engineered CAR T cells and target tumor cells. CRS is reported to occur in up to 50% to 100% of patients receiving CAR T therapy. CRS has many clinical manifestations ranging from minor (fever, fatigue, rash) to severe (hypotension, respiratory failure, coagulopathy, multisystem organ failure, death). Interleukin 6 (IL-6) is thought to be the main inflammatory cytokine in the pathophysiology of CRS. Elevated IL-6 levels are associated with increased vascular leakage, activation of complement, and coagulation cascade as well as myocardial dysfunction. Administration of tocilizumab (IL-6 receptor monoclonal antibody) should be considered in patients with high-grade CRS (requiring vasopressors, FiO2 > 40%).

Distinguishing CRS from other syndromes with similar presentations, such as septic shock, is challenging. Therefore, broad-spectrum antibiotics should be the first-line therapy administered to each CAR T patients with new-onset hemodynamic or respiratory instability. Delaying antibiotic treatment while awaiting the clinical benefit of tocilizumab or confirming infection results in high mortality rates. Corticosteroids are the mainstay of treatment for high-grade CAR T neurotoxicity. In this patient, somnolence is likely related to hypotension, fever, and CRS, and if improved with fluid, vasopressors, and antibiotics, treatment with corticosteroids is not indicated. 


  1. Le RQ, Li L, Yuan W, et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or lifethreatening cytokine release syndrome. Oncologist. 2018;23(8):943-947.
  2. Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor Tcell therapy—assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47-62.
  3. Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018;11(35):e1-e12.