CXCL-9 and IL-18: Potential Biomarkers for Efficacy Evaluation in Refractory Hemophagocytic Lymphohistiocytosis Treated with RED (Ruxolitinib, Emapalumab and Dexamethasone)

Hemophagocytic lymphohistiocytosis (HLH) is a severe disorder characterized by excessive inflammation of cytokines. More than 30% refractory to frontline therapy. Unfortunately, there is no standard second-line regimen for HLH, and around 30% patients showed no responses to current salvage treatments. However, little study reported the alternative therapy and the changing time point for refractory patients. This study retrospectively analyzed the efficacy and safety of the RED (Ruxolitinib Emapalumab, and dexamethasone) regimen in 15 refractory HLH patients who failed to respond to at least twice salvage therapies. Overall, eight (53.3%) patients achieved better remission after RED regimen, of which four patients received HSCT. The level of CXCL-9 and IL-18 before RED treatment showed a significant difference between PR and PD patients, which suggested patients with high level of CXCL-9 and IL-18 may benefit from RED. By analysis of 8 PR HLH, we also found that except white blood cell, Hb and Fbg, the level of AST, CXCL-9 and Ca²⁺ remission after two weeks of RED treatment. We didn't observe grade 3 or higher adverse effects related to the RED regimen. This is the first comprehensive research of RED in HLH, represents a viable and safe alternative treatment for salvaging R HLH.

No relevant conflicts of interest to declare.