Emapalumab plus conventional therapy with or without ruxolitinib for pediatric hemophagocytic lymphohistiocytosis: a single center retrospective study.

BACKGROUND

Hemophagocytic lymphohistiocytosis (HLH) is a rare, highly fatal hyperinflammatory syndrome characterized by an uncontrolled cytokine cascade. Traditional chemotherapy leaves 30% of patients unresponsive, and its side effects are significant. Precise targeted therapies are highly anticipated. Emapalumab is a monoclonal antibody targeting interferon-γ, while ruxolitinib is a JAK1/2 inhibitor, and their application in HLH treatment is gaining attention.

METHODS

We retrospectively collected clinical data from pediatric HLH patients who received emapalumab added to conventional therapy, with or without ruxolitinib, at our hospital between June 1, 2022, and June 1, 2024. Treatment efficacy, safety, improvement in clinical parameters, and causes of death were analyzed.

RESULTS

A total of 10 pediatric patients were included: 7 with refractory disease, 2 with relapsed disease, and 1 with newly diagnosed disease. EBV-associated HLH was observed in 6 of the 10 patients. All patients received emapalumab added to conventional therapy, and 7 patients additionally received ruxolitinib. The median follow-up duration was 164 days (range, 19-473 days). Among the 10 patients, 5 achieved remission. The response rates for fever, hypofibrinogenemia, neutropenia, hyperbilirubinemia, and elevated transaminases were 6/6, 5/5, 8/9, 4/7, and 6/10, respectively. Among patients with relapsed/refractory disease, the remission rate was 2/3 with emapalumab plus conventional therapy alone and 2/6 with the further addition of ruxolitinib. In patients with non-EBV-associated HLH, the corresponding remission rates were 1/2 and 2/2, respectively. In patients with EBV-associated HLH, the rates were 1/1 and 1/5, respectively.

CONCLUSIONS

In this small-sample retrospective study, emapalumab showed a more pronounced trend toward alleviating fever, hypofibrinogenemia, and neutropenia than toward improving liver function among pediatric HLH patients. Adding ruxolitinib to the combination of emapalumab and conventional therapy did not demonstrate a clear additional clinical benefit, particularly in the EBV-associated HLH and relapsed/refractory subgroups. These findings are constrained by the study design and sample size and necessitate validation in larger, prospective studies.