Work

Clinical and Cytokine Features of Immune Effector Cell–Associated Hemophagocytic Lymphohistiocytosis–Like Syndrome

Year: 2025

Type: article

Abstract: Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a poorly characterized inflammatory toxicity of chimeric antigen receptor (CAR) T cells with high risk of mortality. In this study, we describe IEC-HS manifestations in patients with large B-cell lymphoma and B-cell acute lymphoblastic leukemia after CD22-directed CAR T cells. IEC-HS occurred in 19 of 54 patients (35%), including 11 grade 1 and 8 grade 2 or higher. IEC-HS was associated with higher nonrelapse mortality (NRM) yet lower relapse rates. CAR T-cell expansion in peripheral blood was significantly associated with IEC-HS severity. Cytokine profiling identified 41 cytokines primarily related to the IFNγ, TNFα, and IL1 families that significantly correlated with IEC-HS severity. We developed a parsimonious model composed of IFNγ, IL10, and IL1RA that correlated with grade 2+ IEC-HS on day 14, outperforming the full signature (AUC 0.93 vs. 0.75, P = 0.038). Thus, a cytokine signature with potential prognostic utility helps distinguish IEC-HS from inflammatory toxicities with overlapping symptoms. SIGNIFICANCE: IEC-HS is a serious inflammatory toxicity of CAR T cells. We demonstrate that IEC-HS after CD22-directed CAR T-cell therapy is associated with lower rates of relapse yet higher NRM. CAR T-cell expansion and a 41-cytokine signature are associated with IEC-HS, and a simplified signature of IFNγ, IL10, and IL1RA precedes severe disease. See related commentary by Rocco and Shah, p. 163.

Source: Blood Cancer Discovery

DOI: 10.1158/2643-3230.bcd-25-0262