Anakinra for hemophagocytic lymphohistiocytosis: A real-world, multicenter retrospective study on efficacy, safety, and response durability

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of excessive inflammation driven by immune dysregulation. Current standard etoposide-based chemotherapy regimens can control the disease, but their significant toxicities limit clinical use, especially in patients with poorer fitness or contraindications, so there is an urgent clinical need for safer, more rapidly-acting targeted treatment options. Anakinra, an interleukin-1 (IL-1) receptor antagonist, offers a new direction for the treatment of HLH. The aim of this study was to evaluate its real-world efficacy, safety and remission characteristics in Chinese patients with HLH. Method: This retrospective, multicenter study enrolled 18 HLH patients treated with Anakinra from January 2025 to August 2025 (data cutoff: April 2025). The primary endpoint was the overall remission rate (ORR), including complete remission (CR), partial remission (PR), or disease improvement. Secondary endpoints included time to first remission, duration of remission, and proportion of glucocorticoid reductions ≥50%. Result: A total of 18 patients (median age 37.6 years; 16 female) were included in the analysis. At the latest follow-up, the ORR was 83.3% (15/18), including 2 CR (11.1%) and 13 PR (72.2%). The onset of action was rapid, with a median time to first response of just 1.0 week, and 14 patients (77.8%) achieved response within the first week of treatment. A significant glucocorticoid-sparing effect was observed, as 13 patients (72.2%) achieved a ≥50% dose reduction with a median time of 1.0 week. All patients with fever at baseline (3 cases) resolved their fever within 1 week. However, the key finding of this study was the limited durability of remission, with a median duration of remission (DOR) of only 1.0 week. In terms of safety, Anakinra was generally well tolerated, with no drug-related serious adverse events or treatment interruptions observed during the study period. Conclusion: Anakinra can rapidly control disease progression and significantly reduce steroid use in real-world treatment of HLH, demonstrating good short-term efficacy. However, the duration of remission is short, suggesting that combination therapy or prolonged use may be necessary to consolidate efficacy. Although the sample size is limited and the study is retrospective, this research provides important reference for the clinical application of Anakinra in the treatment of HLH.