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

Clinical and Cytokine Features of Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome. Blood cancer discovery Srinagesh, H. K., Kramer, A. M., Baird, J. H., Reschke, A., Sahaf, B., Cancilla, J., Syal, S., Su, Y. J., Agarwal, N., Jensen, A. M., Schultz, L. M., Jeyakumar, N., Ramakrishna, S., Davis, K. L., Dahiya, S., Feldman, S. A., Mackall, C. L., Muffly, L., Miklos, D. B., Frank, M. J. 2025

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.

View details for DOI 10.1158/2643-3230.BCD-25-0262

View details for PubMedID 41411617