Biological therapies for hemophagocytic lymphohistiocytosis: current knowledge and future perspectives

ABSTRACTIntroduction Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with a dismal prognosis. The underlying causes of HLH are diverse. However, the overabundance of cytokines was shared by all forms of HLH. Cytokine-targeted biotherapies have been increasingly used in HLH treatment.Areas covered In this review, we aim to provide an overview of biological treatment options for HLH.Expert opinion Biological therapies offer alternative treatment options for patients with refractory/relapsed HLH or who are intolerant to conventional chemotherapies. As a complement to traditional treatment, biological agents improve response rates, maintain more protracted periods of remission, and reduce treatment related toxicity. A combination of biological agents may be a promising direction for HLH treatment. However, they may induce HLH to deteriorate and even trigger HLH.KEYWORDS: Hemophagocytic lymphohistiocytosisbiological therapyJanus kinaseIFN-γCytokine Article highlights HLH is a life-threatening disease with various underlying conditions.Emapalumab has demonstrated efficacy and safety in pHLH.JAK inhibitors in combination with chemotherapies contribute to improving efficacy and reducing treatment-related toxicityAnakinra is the preferred biological therapy in autoimmune disease related HLH.Biological therapies may induce HLH to deteriorate and even trigger HLH.The combination of biological agents is a promising direction for HLH treatment.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was funded by the National Natural Science Foundation of China (82170122) and (82100351).