Emapalumab in pediatric patients with high-grade cytokine release syndrome associated with CAR T-cell therapy.
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BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy significantly improves the prognosis of a variety of hematological 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°C, 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.