Goda Shiho, Tsuji Taisuke, Matsumoto Yosuke, Shiotsu Shinsuke, Tanaka Shunya, Suga Yoshifumi, Fujii Hiroyuki, Matsuyama Aosa, Omura Ayaka, Yuba Tatsuya, Takumi Chieko, Hiraoka Noriya
Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
Curr Probl Cancer. 2021 Jun;45(3):100686. doi: 10.1016/j.currproblcancer.2020.100686. Epub 2020 Dec 3.
Programmed cell death protein 1 immune checkpoint inhibitor is an effective treatment for non-small cell lung cancer. Although hematological immune-related adverse events induced by antiprogrammed-cell-death-protein-1 immunotherapy have been reported, they are rare, and there remain many unknowns. We report the case of a 77-year-old woman with non-small cell lung cancer and pembrolizumab-induced danazol-dependent aplastic anemia. Sixteen days after she received pembrolizumab with carboplatin and pemetrexed as first-line treatments, she developed pancytopenia, including severe thrombocytopenia (1 × 10/L) with oral bleeding, epistaxis, and systemic purpura. We initially diagnosed immune-related thrombocytopenia based on an elevated level of platelet-associated immunoglobulin G (922ng/10 cells), but her thrombocytopenia was refractory to prednisolone (1mg/kg) and thrombopoietin receptor agonists. We eventually diagnosed aplastic anemia based on the findings of bone marrow hypoplasia. Treatment with cyclosporine and danazol 300mg (7.5mg/kg) was initiated. Eighteen days later, her blood cell count increased, and we reduced danazol to 100mg. Twenty-four days after the reduction of danazol, her platelet count dropped again to 14 × 10/L; subsequently, increasing danazol improved her platelet count in a few days. Although aplastic anemia was recovered, she died owing to lung cancer progression. In this case, the thrombocytopenia was noticeable initially; however, pancytopenia appeared a month later, and we diagnosed her with aplastic anemia. Platelet counts improved rapidly with the use of danazol. No effective treatment has yet been established for aplastic anemia induced by antiprogrammed-cell-death-protein-1 immunotherapy, but our case suggests that danazol is an effective therapy.
程序性细胞死亡蛋白1免疫检查点抑制剂是治疗非小细胞肺癌的有效方法。尽管已有抗程序性细胞死亡蛋白1免疫疗法诱导血液学免疫相关不良事件的报道，但此类事件罕见，仍有许多未知之处。我们报告了1例77岁非小细胞肺癌女性患者，其因帕博利珠单抗诱发了达那唑依赖性再生障碍性贫血。在她接受帕博利珠单抗联合卡铂和培美曲塞作为一线治疗16天后，出现全血细胞减少，包括严重血小板减少（1×10⁹/L），伴有口腔出血、鼻出血和全身性紫癜。我们最初根据血小板相关免疫球蛋白G水平升高（922ng/10⁹细胞）诊断为免疫相关性血小板减少，但她的血小板减少对泼尼松龙（1mg/kg）和血小板生成素受体激动剂治疗无效。最终，根据骨髓发育不全的结果，我们诊断为再生障碍性贫血。开始使用环孢素和300mg（7.5mg/kg）达那唑进行治疗。18天后，她的血细胞计数增加，我们将达那唑减至100mg。达那唑减量24天后，她的血小板计数再次降至14×10⁹/L；随后，增加达那唑剂量在数天内改善了她的血小板计数。尽管再生障碍性贫血有所恢复，但她因肺癌进展而死亡。在该病例中，最初血小板减少较为明显；然而，1个月后出现全血细胞减少，我们诊断她为再生障碍性贫血。使用达那唑后血小板计数迅速改善。对于抗程序性细胞死亡蛋白1免疫疗法诱发的再生障碍性贫血，尚未确立有效的治疗方法，但我们的病例提示达那唑是一种有效的治疗方法。
