Successful treatment of steroid-refractory immune checkpoint inhibitor-related pneumonitis with triple combination thera
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ORIGINAL ARTICLE
Successful treatment of steroid‑refractory immune checkpoint inhibitor‑related pneumonitis with triple combination therapy: a case report Hirofumi Utsumi1 · Jun Araya1 · Keitaro Okuda1 · Junko Watanabe1 · Daisuke Takekoshi1 · Yu Fujita1 · Mitsuo Hashimoto1 · Hiroshi Wakui1 · Shunsuke Minagawa1 · Takanori Numata1 · Hiromichi Hara1 · Kazuyoshi Kuwano1 Received: 5 January 2020 / Accepted: 29 April 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Immune checkpoint inhibitor (ICI)-related pneumonitis is a relatively rare but clinically serious and potentially life-threatening adverse event. The majority of cases can be managed by drug discontinuation, with the administration of corticosteroids added in severe cases. However, worsening of pneumonitis can develop in a subset of patients despite treatment with high doses of corticosteroids. We herein report a case of steroid-refractory ICI-related pneumonitis in a recurrent non-small cell lung cancer (NSCLC) patient treated with pembrolizumab that was successfully improved by triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide). After 3 weeks of initial pembrolizumab administration, the patient was diagnosed with ICI-related pneumonitis. Chest computed tomography (CT) showed patchy distributed bilateral consolidation and ground-glass opacities (GGOs) with traction bronchiectasis and bronchiolectasis resembling the diffuse alveolar damage (DAD) radiographic pattern. Although methylprednisolone pulse therapy was initiated, worsening of respiratory failure resulted in the patient being transferred to the intensive care unit. Because of an insufficient therapeutic response to high-dose corticosteroids, tacrolimus and cyclophosphamide pulse therapy were additively performed as triple combination therapy according to the treatment strategy for pulmonary complications of clinically amyopathic dermatomyositis (CADM). In response to this triple combination therapy, the patient’s respiratory condition gradually improved, and chest CT showed the marked amelioration of pulmonary opacities. This is the first report suggesting the efficacy of triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide) for steroid-refractory ICI-related pneumonitis complicated with respiratory failure. Keywords Immune checkpoint inhibitor · Pembrolizumab · Pneumonitis · Steroid-refractory · Non-small cell lung cancer · Triple combination therapy Abbreviations AIP Acute interstitial pneumonia ALK Anaplastic lymphoma kinase BAL Bronchoalveolar lavage BNP B-type natriuretic peptide CADM Clinically amyopathic dermatomyositis CI Confidence interval COP Cryptogenic organizing pneumonia * Hirofumi Utsumi [email protected] 1
Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, 3‑19‑18 Nishi‑shinbashi, Minato‑ku, Tokyo 105‑8461, Japan
CT Computed tomography CTCAE Common Toxicity Criteria for Adverse Events CTLA-4 Cytotoxic T-lymphocyte
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