A case of non-neutropenic invasive pulmonary aspergillosis under immune checkpoint inhibitor therapy for malignant melanoma.

The patient was a 70-year-old man with diabetes mellitus, alcoholic liver disease and bronchial asthma treated with corticosteroid and long-acting ß-agonist inhalants. He had also been treated with nivolumab for advanced malignant melanoma for two years with a partial response. He presented to our department with intractable cough, which was attributed to uncontrolled bronchial asthma. Two weeks later, he presented with a high fever and worsened cough. He was diagnosed with bacterial pneumonia based on severe inflammation revealed by laboratory tests and right upper lung consolidation on chest radiography. Antibiotics via either oral or parenteral administration were ineffective and no pathogen was detected in sputum or blood cultures. Based on the air-crescent sign observed on chest computed tomography and a diffuse pseudomembranous lesion on the airway epithelium that was observed via bronchoscopy along with positive serum Aspergillus antigen, a clinical diagnosis of invasive pulmonary aspergillosis (IPA) was made and liposomal amphotericin B was initiated. Three days later, the patient developed massive hemoptysis, and he died of respiratory failure. Later, aspergillus-like mycelia were observed in the pathology of bronchial biopsy, supporting the clinical diagnosis of IPA. Although the use of immune checkpoint inhibitors has been reported to be beneficial for patients with some infectious diseases, it does not seem to be the case for patients with other infectious diseases including our patient.

Dramatic response to alectinib in an ALK-positive LCNEC patient with a poor performance status: A case report.

The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene, a driver mutation in lung carcinoma, is fairly common in lung adenocarcinoma but rare in large cell neuroendocrine carcinoma (LCNEC). Here we report a case of stage IV LCNEC positive for this fusion gene in a patient with a poor performance status (PS) who was effectively treated with alectinib. The patient was a 72-year-old non-smoking man diagnosed as LCNEC with multiple metastases. Because of his poor PS, cytotoxic chemotherapy was not indicated, but he was later found to be positive for the ALK fusion gene and treated with alectinib as first-line therapy. One month later, the tumour had shrunk remarkably, and the therapeutic effect was rated as a partial response. The PS also improved from 4 to 1. Investigating actionable driver mutations seems worth doing for advanced LCNEC, especially if the patient's PS is poor.

Significant therapeutic effectiveness of durvalumab after chemoradiotherapy for a patient with post-operative recurrent pulmonary pleomorphic carcinoma.

Pulmonary pleomorphic carcinoma (PPC) is a poorly differentiated non-small cell lung cancer. Because of its rarity, no standard therapy has been established for advanced disease. We herein report on a 62-year-old man with recurrent post-operative PPC, for whom durvalumab after chemoradiotherapy was effective. He was referred to our hospital because of an abnormal shadow in the right upper lung on chest X-ray. After surgical resection was performed, the imaging and histopathological findings revealed PPC (T4N0M0, stage IIIA) with elevated expression of programmed cell death-ligand 1 (PD-L1). A metastasis was found in the left hemithorax 22 months later, and chemoradiotherapy consisting of 60 Gy of radiation and cisplatin plus tegafur/gimeracil/oteracil potassium was administered. Durvalumab was then begun as consolidation therapy. The efficacy of the treatments has continued for longer than 10 months. This case suggests that multidisciplinary treatment with chemoradiotherapy and consolidation immunotherapy may improve the prognosis of locally advanced PPC.

Myositis induced by durvalumab in a patient with non-small cell lung cancer: A case report.

Immune checkpoint inhibition is associated with a broad spectrum of immune toxicities referred to as immune-related adverse events (irAEs). Myositis is known to be a potentially fatal irAE. Here, we report a case of immune-related myositis after the administration of durvalumab. A 60-year-old man with stage IIIA lung adenocarcinoma was treated with durvalumab after concurrent chemoradiation therapy. After the third dose of durvalumab, his serum CK level was elevated, and soon thereafter myalgia of the proximal muscles and blepharoptosis were observed. We diagnosed immune-related myositis based on the results of pathological examination and initiated systemic corticosteroid therapy. His symptoms then improved and the serum CK level immediately dropped to within a normal range. Clinicians should be aware of possible myositis during the early phase of durvalumab therapy.