Secondary hemophagocytic lymphohistiocytosis associated with adjuvant pembrolizumab therapy in a young patient with triple-negative breast cancer: a case report with literature review.

Purpose: Secondary hemophagocytic lymphohistiocytosis (HLH) associated with pembrolizumab is a rare immune-related adverse event (irAE). It features a potential life-threatening status including fever and a hyperinflammatory reaction caused by natural killer cells, CD8 + cytotoxic T cells, and antigen-presenting cells leading to multiorgan failure. Secondary HLH is described for immune checkpoint inhibitor (ICI) therapy. Most descriptions refer to patients with melanoma or lung cancer. We report about a 32 year-old patient with secondary HLH associated with adjuvant pembrolizumab therapy according to the Keynote-522 protocol. It was successfully treated with prednisolone.

Methods: We performed a literature review in PubMed including the terms "HLH OR hemophagocytic lymphohistiocytosis AND breast cancer". We found four other cases meeting the inclusion criteria (abstract available in English, breast cancer patient, HLH related to ICI therapy).

Results: Apart from the case report, the review featured main aspects about the diagnosis (HScore, histopathological assessment), onset of HLH, and medical treatment. The review indicated that secondary ICI induced HLH in breast cancer patients may be associated with complete response according to their tumor burden. Most cases are reported with an onset of secondary HLH within the neoadjuvant treatment phase and were treated analogously to the Keynote-522 protocol. Our case showed an onset almost 1 year after the initiation of pembrolizumab therapy.

Conclusion: Gyneco-oncologist should be aware of secondary HLH during pembrolizumab therapy and should assess patients with persistent fever using the HScore to diagnose secondary HLH early.