Background：Uncontrolled immune activation and severe inflammation are the hallmarks of hemophagocytic lymphohistiocytosis (HLH) with no treatment response in approximately 30% of patients. With no established salvage treatment, ability of burton tyrosine kinase (BTK) inhibitors to resolve inflammations might be relevant treatment option for HLH. Here, we evaluated the efficacy and safety of zanubrutinib in patients with refractory/relapsed HLH.
Methods：In this single-center, single arm, prospective trial, HLH patients were treated with 160 mg zanubrutinib twice daily for 8 weeks. Efficacy in terms of overall response (OR), complete response (CR) and partial response (PR) at 2, 4, 6, and 8 weeks along with safety was assessed.
Results: A total of 16 patients were enrolled who had a median age of 33.5 years (range 19-74 years) and most patients had connective tissue diseases (n=9; 56.3%). Overall response (OR) after 2 weeks of treatment was 86.7% among with 1 (6.7%) and 12 (80%) patients achieved CR and PR respectively. After 8 weeks, 8 patients were excluded due to various clinical reasons and all the remaining 8 patients achieved CR. Among the 9 patients with macrophage activation syndrome (MAS), 5 (62.5%) achieved CR at 8 weeks. Proinflammatory cytokines, IL-1, IL-10, and IFN-γ significantly decreased (P<0.05) 2 weeks post-zanubrutinib. Fatigue, ecchymosis, and nausea were the most common adverse events and 1 patient died due to cerebral infarction combined with cerebral hemorrhage.
Conclusions: Zanubrutininb showed promising efficacy making it an effective candidate for HLH salvage therapy. However, further confirmations with large-scale studies would be welcoming.
No relevant conflicts of interest to declare.
Zanubrutinib
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal