Interferon-γ blockade in CAR T-cell therapy–associated macrophage activation syndrome/hemophagocytic lymphohistiocytosis

Tisagenlecleucel (tisa-cel) is a CD19 chimeric antigen receptor (CAR) T-cell therapy that has shown exceptional efficacy in young individuals with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL), leading to an overall remission rate of more than 80%. 1 Among complications of CAR T-cell therapy, macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH) is a life-threatening toxicity characterized by hyperinflammation and manifesting as persistent fevers, splenomegaly, endorgan damage, cytopenias, coagulopathy, and hypofibrinogenemia. MAS/HLH can be considered a distinct variant of cytokine release syndrome (CRS) that commonly occurs after CAR T-cell therapy.