ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicNext-generations of CAR-T Cell Therapy in Hematologic MalignanciesView all 3 articles
Emapalumab in Pediatric Patients with High-grade Cytokine Release Syndrome Associated with CAR T-cell Therapy
Provisionally accepted
Jing Zhang
Wenhua Shi
Jing YangJuan QianMeng SuKang AnTianyi WangRujun JiaChengming Fei*
Yanjing Tang*Benshang Li*- Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Background: Chimeric antigen receptor T (CAR-T) cell therapy significantly improves the prognosis of a variety of haematological malignancies; however, its broader application in clinical practice is hindered by adverse events, particularly cytokine release syndrome (CRS). Moreover, the selection of treatment strategies for patients with high-grade CRS must be meticulously tailored. Emapalumab, a fully human IgG1 monoclonal antibody targeting IFN-γ, has been proposed to have clinical benefit in CRS. Methods: In this retrospective study, we conducted a comprehensive analysis of clinical and laboratory parameters in 38 pediatric patients who failed low-dose glucocorticoids monotherapy, tocilizumab monotherapy or glucocorticoid-tocilizumab combination therapy, following treatment with investigational CAR-T products. Results: Emapalumab significantly improved both clinical symptoms and laboratory parameters. The rapid decrease in mean temperature (39.61 vs. 38.38℃, P < 0.001) and levels of inflammatory markers including IL-2 (32.35 vs. 11.94 pg/ml, P < 0.001), IL-10 (222.29 vs. 86.09 pg/ml, P = 0.018), TNF-α (4.17 vs. 2.94 pg/ml, P = 0.032), and IFN-γ (21984.11 vs. 674.87 pg/ml, P < 0.001) indicated the remarkable scavenging efficacy of emapalumab against cytokine storm following CAR-T therapy. Additionally, both mean CAR-T cell counts (549.95 vs. 8.16 cell/μl, P < 0.001) and the ratio of CAR-T to CD3+ (11.3% vs. 36.54%, P < 0.001) in peripheral blood increased significantly, demonstrating that the administration of emapalumab didn’t seem to have a significant negative impact on the proliferation of CAR-T cells. The median EFS and OS were both not reached, with an EFS rate of 76.9% (95%CI, 63.8-92.6) and with an OS rate of 80.1% (95% CI, 67.7-94.6) at 6 months. Throughout the treatment course, no direct evidence of emapalumab-related safety risks was observed. Conclusion: Emapalumab seems to serve as an effective salvage therapy for patients experiencing high-grade CRS with inadequate response to low-dose glucocorticoids and/or tocilizumab following CAR-T therapy. These data supported the use of emapalumab in high-grade CRS as well as provide rationale for future prospective studies.
Keywords: Chimeric antigen receptor T-cell, cytokine release syndrome, efficacy, Emapalumab, IFN-γ, Safety
Received: 08 Aug 2025; Accepted: 02 Feb 2026.
Copyright: © 2026 Zhang, Shi, Yang, Qian, Su, An, Wang, Jia, Fei, Tang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chengming Fei
Yanjing Tang
Benshang Li
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