Mizuta Haruki, Nakano Eiji, Takahashi Akira, Koyama Takafumi, Namikawa Kenjiro, Yamazaki Naoya
Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.
Dermatol Ther. 2020 May;33(3):e13321. doi: 10.1111/dth.13321. Epub 2020 Mar 25.
Combination therapy with nivolumab + ipilimumab was recently approved for treating unresectable cases of malignant melanoma. In spite of the high response rate, it is associated with a high incidence of serious adverse events, including immune-related hemophagocytic syndrome/hemophagocytic lymphohistiocytosis (irHPS/HLH), a difficult to diagnose rare disease. This is the first report of this disease in an Asian malignant melanoma patient treated with nivolumab + ipilimumab. A 69-year-old Japanese woman with unresectable malignant melanoma was treated with nivolumab + ipilimumab. Following the combined therapy, her fever and symptoms of malaise occurred, and she visited to our hospital's emergency department. Blood tests revealed significant liver dysfunction, anemia, and thrombocytopenia. We suspected irHPS/HLH, based on tests revealing decreased fibrinogen and significantly increased ferritin. Bone marrow biopsy revealed numerous macrophages and high hemophagocytosis levels. After 50 mg prednisolone (1 mg/kg per day) was administered, fever and cytopenia markedly improved. irHPS/HLH has a high rate of coagulation abnormalities accompanied by hypertriglyceridemia and hypofibrinogenemia, which are unlikely to occur in adult HPS/HLHs. Because irHPS/HLH responds better to steroids than other secondary HPS/HLHs, we expect a complete cure with steroids. Quick diagnosis and appropriate treatment based on clinical symptoms and laboratory tests are needed in suspected cases.
纳武单抗联合伊匹单抗的联合疗法最近被批准用于治疗不可切除的恶性黑色素瘤病例。尽管缓解率很高，但它与严重不良事件的高发生率相关，包括免疫相关噬血细胞综合征/噬血细胞性淋巴组织细胞增生症（irHPS/HLH），这是一种难以诊断的罕见疾病。这是首例在接受纳武单抗联合伊匹单抗治疗的亚洲恶性黑色素瘤患者中出现这种疾病的报告。一名69岁患有不可切除恶性黑色素瘤的日本女性接受了纳武单抗联合伊匹单抗治疗。联合治疗后，她出现发热和全身不适症状，并前往我院急诊科就诊。血液检查显示严重肝功能障碍、贫血和血小板减少。基于纤维蛋白原降低和铁蛋白显著升高的检查结果，我们怀疑为irHPS/HLH。骨髓活检显示大量巨噬细胞和高噬血细胞水平。给予50毫克泼尼松龙（每天1毫克/千克）后，发热和血细胞减少明显改善。irHPS/HLH伴有高甘油三酯血症和低纤维蛋白原血症的凝血异常发生率很高，这在成人HPS/HLH中不太可能发生。由于irHPS/HLH对类固醇的反应比其他继发性HPS/HLH更好，我们期望用类固醇实现完全治愈。对于疑似病例，需要根据临床症状和实验室检查进行快速诊断和适当治疗。
