Tozuka Takehiro, Sugano Teppei, Noro Rintaro, Takano Natsuki, Hisakane Kakeru, Takahashi Satoshi, Tanaka Toru, Kashiwada Takeru, Takeuchi Susumu, Kunugi Shinobu, Minegishi Yuji, Saito Yoshinobu, Kubota Kaoru, Seike Masahiro, Gemma Akihiko
Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan.
Department of Analytic Human Pathology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Oxf Med Case Reports. 2018 Oct 22;2018(11):omy094. doi: 10.1093/omcr/omy094. eCollection 2018 Nov.
An 82-year-old man with a recurrence of pulmonary pleomorphic carcinoma was treated with pembrolizumab. He achieved partial response after three cycles of pembrolizumab. However, he developed febrile neutropenia. A bone marrow aspiration sample revealed a decrease of mature neutrophils, and anti-neutrophil antibody was detected in blood. Computed tomography scans revealed consolidation in the right lung. Pathological findings in lung biopsy tissue revealed organizing pneumonia. Pembrolizumab-induced agranulocytosis and interstitial lung disease (ILD) were diagnosed. We initiated antibacterial therapy and granulocyte colony-stimulating factor (G-CSF). The neutrophil count immediately increased, and the fever decreased. The improvement of ILD was achieved without using systemic steroids. Moreover, the patient developed ocular myasthenia gravis induced by pembrolizumab. This is the first case report of pembrolizumab-induced agranulocytosis. Agranulocytosis was improved by administration of G-CSF without using systemic steroids. However, further studies are needed to determine the optimal treatment for patients with anti-neutrophil antibody whose tumor has progressed.
一名82岁的肺多形性癌复发男性接受了帕博利珠单抗治疗。在接受三个周期的帕博利珠单抗治疗后,他获得了部分缓解。然而,他出现了发热性中性粒细胞减少症。骨髓穿刺样本显示成熟中性粒细胞减少,血液中检测到抗中性粒细胞抗体。计算机断层扫描显示右肺实变。肺活检组织的病理结果显示为机化性肺炎。诊断为帕博利珠单抗诱导的粒细胞缺乏症和间质性肺病(ILD)。我们开始了抗菌治疗和粒细胞集落刺激因子(G-CSF)治疗。中性粒细胞计数立即增加,发热减退。未使用全身性激素就实现了ILD的改善。此外,该患者出现了帕博利珠单抗诱导的眼肌型重症肌无力。这是帕博利珠单抗诱导的粒细胞缺乏症的首例病例报告。通过给予G-CSF,未使用全身性激素,粒细胞缺乏症得到了改善。然而,对于肿瘤进展的抗中性粒细胞抗体患者,需要进一步研究以确定最佳治疗方案。