Re: Hematological immune related adverse events after treatment with immune checkpoint inhibitors

We read with great interest the article by Kramer et al. [ ] on the haematological adverse effects associated with immune checkpoint inhibitors (ICIs). The authors have extensively discussed several rare but clinically significant hematological adverse effects that may also prove to be fatal in some cases. The adverse effect that drew our attention, in particular, is haemophagocytic lymphohistiocytosis (HLH). HLH is a potentially fatal clinical syndrome that results from a severe, uncontrolled hyperinflammatory state, which may be triggered by several causes such as infection, malignancy, drugs and so on [ ]. Patients may have a non-specific clinical picture that includes, but is not limited to, a triad of fever, cytopenias and hepatosplenomegaly, but atypical or overlapping presentations are common [ ]. ICIs are known to be associated with several immune-related adverse events (irAEs) including HLH or ICI-related HLH (ICI-HLH). The underlying mechanism proposed in this regard is the inhibition of cytotoxic T-cell activity by ICIs, which results in a pathologic hyperinflammatory state [ ]. The authors determined the frequency of HLH to be 2 of 50 (4%) in their study cohort. However, the real magnitude of occurrence of ICI-HLH is unknown as it is a poorly understood clinical phenomenon and existing data majorly come from isolated case reports.