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━━ Background. Pembrolizumab, an immune checkpoint inhibitor, has been used as a standard treatment for non-small cell lung cancer, and there have been reports of interstitial lung injury (checkpoint inhibitor pneumonitis; CIP) due to the use of immune checkpoint inhibitors. Case. A 78-year-old man was found to have a tumor shadow in the lingua of the left lung by whole-body computed tomography (CT). After a close examination, we made a diagnosis of lung squamous cell carcinoma cT2aN2M1a stage IVA, PD-L1 tumor proportion score: 5%. He underwent first-line chemotherapy, which consisted of carboplatin and nab-paclitaxel. After the disease progressed, he received second-line chemotherapy with pembrolizumab, and he showed a complete response. He had dyspnea on exertion 64 weeks after starting pembrolizumab. Chest X-ray and chest CT showed diffuse groundglass shadow, suggesting immune-related pulmonary disorder. He was diagnosed with alveolar hemorrhaging based on the properties of bronchoalveolar lavage fluid. He discontinued pembrolizumab and underwent steroid pulse therapy. Subsequently, the ground-glass shadow improved. There was no recurrence even after steroid tapering, and no tumor progression after discontinuation of pembrolizumab. Conclusion. Our patient developed alveolar hemorrhaging as an immune related adverse event after showing a long-term response to pembrolizumab. Although immune-related pulmonary disorders are usually observed relatively early after administration, close attention should be paid in cases with a long-term response. (JJLC. 2020;60:353-357) KEY WORDS━━ Pembrolizumab, Alveolar hemorrhage, Long-term response, Non-small cell lung cancer Corresponding author: Naoki Shijubou. Received March 25, 2020; accepted May 13, 2020. 要旨━━背景.免疫チェックポイント阻害薬であるペ ムブロリズマブは非小細胞肺癌に対する標準治療として 用いられているが,免疫チェックポイント阻害薬使用に よる肺障害(checkpoint inhibitor pneumonitis:CIP)の 報告が散見される.症例.78歳,男性.全身 CTで左舌 区に腫瘤影を認めた.精査の結果,肺扁平上皮癌 cT2aN2M1a,Stage IVA,PD-L1 tumor proportion score 5%と診断し,初回治療としてカルボプラチン+ナブパ クリタキセルを開始した.病勢増悪後は 2次治療として ペムブロリズマブを開始し,完全奏功が得られた.ペム ブロリズマブ開始 64週後に労作時呼吸困難が出現した. 胸部 X線写真,胸部 CTでびまん性のすりガラス影を認 め,CIPを疑った.気管支肺胞洗浄液の性状から肺胞出血 と診断し,ペムブロリズマブは中止しステロイドパルス 療法を施行した.ステロイド治療開始後,すりガラス影 は改善した.ステロイド漸減後も再燃なく,ペムブロリ ズマブ中止後も肺癌の病勢悪化はない.結論.ペムブロ リズマブ長期奏功後に免疫関連有害事象として肺胞出血 函館五稜郭病院 1呼吸器内科,2病理診断科;3札幌医科大学医学 部呼吸器・アレルギー内科学講座. 論文責任者:四十坊直貴. 受付日:2020年 3月 25日,採択日:2020年 5月 13日. (肺癌.2020;60:353-357) 2020 The Japan Lung Cancer Society Alveolar Hemorrhage After Long-term Response to Pembrolizumab―Shijubou et al 354 Japanese Journal of Lung Cancer―Vol 60, No 4, Aug 20, 2020―www.haigan.gr.jp Table 1. The Laboratory Findings at Hospitalization Hematology Biochemistry Serology WBC 8300/μl TP 7.2 g/dl CRP 13.51 mg/dl Neut 84.6% Alb 3.4 g/dl RF 3.0 IU/ml Lym 10.0% T-Bil 1.0 mg/dl Anti-nuclear-antibody <40× Eos 0.6% AST 31 U/l MPO-ANCA <1.0 U/ml RBC 436×104/μl ALT 14 U/l PR3-ANCA 1.4 U/ml Hb 13.1 g/dl LDH 403 U/l β-D-glucan 18.8 pg/ml Ht 38.8% ALP 273 U/l Plt 23.4×104/μl CK 102 U/l BUN 28.0 mg/dl Cr 1.07 mg/dl Na 137 mEq/l K 4.1 mEq/l Cl 100 mEq/l KL-6 2430 U/ml SP-D 366 ng/ml を認めた.免疫関連肺障害は投与早期の発症が多いが, 長期奏功中の発症もあるため注意が必要である. 索引用語━━ペムブロリズマブ,肺胞出血,長期奏功, 非小細胞肺癌

A Case of Lung Squamous Cell Carcinoma with Alveolar Hemorrhaging After a Long-term Response to Pembrolizumab