Cytokine release syndrome after CAR T-cell therapy: a review of the literature and our experience

Cytokine release syndrome is an acute systemic inflammatory response triggered by overactivation of the immune system that may be initiated by a variety of factors. The incidence of cytokine release syndrome is high, especially after immunotherapy with chimeric antigen receptor T-cells, which is effective for refractory or recurrent B cell hematological malignancies. Cytokine release syndrome occurs due to a high level of immune activation of lymphocytes, macrophages, or myeloid cells with a subsequent massive release of inflammatory cytokines. After chimeric antigen receptor T-cell therapy, symptoms appear within days of infusion, which correlates with the maximum T-cells expansion. The monocyte-macrophage system, which is the main source of the most important cytokines, plays a key role in pathophysiology. The central mediator of toxicity is interleukin 6. Cytokine release syndrome is presented by fever, hypotension, and hypoxia, severe forms are clinically indistinguishable from sepsis and may lead to multiorgan failure. Because chimeric antigen receptor T-cell immunotherapy is a potentially curative treatment, patients should be provided with full resuscitation care after administration of this therapy. In severe cytokine release syndrome, treatment with tocilizumab is indicated, after which symptoms usually resolve rapidly. The challenge in clinical practice is to differentiate cytokine release syndrome from other serious conditions, which may be concomitant and may require a different therapeutic approach.

Keywords: cytokine release syndrome, immunotherapy, multiple organ failures.