A case of non–small cell lung cancer with danazol-dependent aplastic anemia induced by pembrolizumab

• Published in: Current problems in cancer Vol. 45; no. 3; p. 100686
• Main Authors: Goda, Shiho, Tsuji, Taisuke, Matsumoto, Yosuke, Shiotsu, Shinsuke, Tanaka, Shunya, Suga, Yoshifumi, Fujii, Hiroyuki, Matsuyama, Aosa, Omura, Ayaka, Yuba, Tatsuya, Takumi, Chieko, Hiraoka, Noriya
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2021
• Subjects: Aged; Anemia, Aplastic - chemically induced; Anemia, Aplastic - drug therapy; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Agents, Immunological - adverse effects; Aplastic anemia; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Danazol; Danazol - administration & dosage; Estrogen Antagonists - administration & dosage; Fatal Outcome; Female; Humans; Immune-related adverse events; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lymphatic Metastasis - pathology; Non–small cell lung cancer; Pembrolizumab; ALK; Immune-related adverse events; NSCLC; ITP; PRCA; Aplastic anemia; BRAF; G-CSF; Danazol; ICI; EGFR; TTP; CT; Non–small cell lung cancer; Pembrolizumab; TKI; TPO-RAs; TNF-α; PD-L1; irAE; PD-1; PET; AIHA
• ISSN: 0147-0272; 1535-6345
• DOI: 10.1016/j.currproblcancer.2020.100686

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 × 109/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/107 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 × 109/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.