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

Abstract CAR-T cells targeting CD22 (CAR22) are associated with IEC-HS. However, CAR22-related IEC-HS has not been detailed in LBCL or adults with B-ALL. Here, we describe the manifestations of IEC-HS in patients with LBCL and B-ALL. IEC-HS was common, occurring in 19 out of 54 patients (35%); 8 patients required treatment and 11 patients did not. Development of IEC-HS was associated with a higher non-relapse mortality risk yet lower relapse. CAR expansion in peripheral blood significantly associated with IEC-HS severity. Cytokine profiling identified 41 cytokines primarily related to the IFNg, TNFa and IL1 families that correlated strongly with IEC-HS severity. We developed a parsimonious model composed of IFNg, IL10 and IL1RA that accurately predicted grade 2+ IEC-HS on D+14 better than the full signature (AUC 0.93 vs 0.75, p = 0.038). In summary, we found IEC-HS predicts higher NRM and lower relapse after CAR22 and that cytokine signatures predict severe IEC-HS.