Blood cancer discovery · 2026
Clinical and Cytokine Features of Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome.
СтатьяНазвание и аннотация: Перевод в очереди
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Srinagesh Hrishikesh K, Kramer Anne Marijn, Baird John H, Reschke Agnes, Sahaf Bita, Cancilla Juancarlos, Syal Shriya, Su Yi-Jiun, Agarwal Neha, Jensen Alexandria M, Schultz Liora M, Jeyakumar Nikeshan, Ramakrishna Sneha, Davis Kara L, Dahiya Saurabh, Feldman Steven A, Mackall Crystal L, Muffly Lori S, Miklos David B, Frank Matthew J
Аннотация
UNLABELLED: 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.
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.