Olmes G L, Nigdelis M P, Hamoud B Haj, Solomayer E-F, Bewarder M, Bittenbring J T, Kranzhöfer N, Thurner L, Kim Y-J, Seibold A, Doerk M
Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center, 66421, Homburg, Germany.
Department for Oncology and Hematology, University Hospital Medical School, 66421, Homburg, Germany.
Arch Gynecol Obstet. 2025 Jul 3. doi: 10.1007/s00404-025-08078-4.
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.
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).
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.
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.
与帕博利珠单抗相关的继发性噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的免疫相关不良事件（irAE）。其特征为潜在的危及生命状态，包括发热以及由自然杀伤细胞、CD8 + 细胞毒性T细胞和抗原呈递细胞引起的导致多器官功能衰竭的过度炎症反应。继发性HLH在免疫检查点抑制剂（ICI）治疗中已有描述。大多数描述涉及黑色素瘤或肺癌患者。我们报告了一名32岁的患者，根据KEYNOTE-522方案，其患有与辅助性帕博利珠单抗治疗相关的继发性HLH。该患者通过泼尼松龙成功治愈。
我们在PubMed上进行了文献综述，搜索词为“HLH或噬血细胞性淋巴组织细胞增生症 且 乳腺癌”。我们发现了其他4例符合纳入标准的病例（英文摘要可用，乳腺癌患者，与ICI治疗相关的HLH）。
除病例报告外，该综述还介绍了诊断（HScore、组织病理学评估）、HLH的发病情况和医学治疗的主要方面。该综述表明，乳腺癌患者中继发性ICI诱导的HLH可能与其肿瘤负荷的完全缓解有关。大多数病例报告显示继发性HLH在新辅助治疗阶段发病，并按照KEYNOTE-522方案进行治疗。我们的病例显示在帕博利珠单抗治疗开始近1年后发病。
妇科肿瘤学家应在帕博利珠单抗治疗期间意识到继发性HLH，并应使用HScore对持续发热的患者进行评估，以便早期诊断继发性HLH。
