A case report of nilotinib-induced irreversible interstitial lung disease.

RATIONALE: Nilotinib is a second line tyrosine kinase inhibitor to treat patients with chronic myeloid leukemia after imatinib resistance or intolerance. Drug related pulmonary complication is known to be rare. We discuss a case of nilotinib-induced interstitial lung disease presenting with nonspecific interstitial pneumonia on the unilateral lung. PATIENT CONCERNS: A 46-year-old man with chronic-phase chronic myeloid leukemia presented with cough and weight loss for 2 months. He had been treated with nilotinib for 52 months. DIAGNOSIS: Computed tomography scan showed right lung dominant consolidations, ground glass opacities and traction bronchiectasis. Bronchoalveolar lavage fluid analysis revealed no evidence of infection or malignancy. Surgical lung biopsy specimen was consistent with fibrosing nonspecific interstitial pneumonia. The patient was diagnosed with nilotinib induced interstitial lung disease. INTERVENTIONS: Corticosteroid treatment was initiated with prednisolone (50 mg daily) and slowly tapered down for 2 months. OUTCOMES: Cough improved after the course of corticosteroid treatment. However, fibrotic lung lesions persisted. Reinitiation of nilotinib resulted in the worsening of lung lesions. LESSONS: We report a case of irreversible interstitial lung disease that caused by nilotinib. Clinicians should have suspicion of this potential pulmonary complication in patients with respiratory symptoms and abnormal radiologic findings during nilotinib treatment, albeit rarely.

Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case-control study.

PURPOSE: The immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia-idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis. METHODS: Eleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects. RESULTS: The odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03-0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease. CONCLUSION: The administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.

Anaplastic lymphoma kinase inhibitor related pneumonitis in patients with non-small cell lung cancer: Clinical and radiologic characteristics and risk factors.

Anaplastic lymphoma kinase (ALK) inhibitor-related pneumonitis (ALK-IIP) is relatively rare but sometimes fatal, so the timely diagnosis of ALK-IIP is important for enabling prompt management. However, the detailed radiologic characteristics and clinical course of ALK-IIP are still unclear. This study was performed to investigate the clinical and radiologic characteristics and risk factors of ALK-IIP in patients with non-small cell lung cancer (NSCLC).A total of 250 NSCLC patients who had been treated with ALK inhibitors were retrospectively enrolled. Chest computed tomography (CT) was classified into 4 CT patterns using the 2013 guideline for idiopathic interstitial pneumonia: cryptogenic organizing pneumonia (COP), hypersensitivity pneumonitis (HP), acute interstitial pneumonia (AIP), and nonspecific interstitial pneumonia. Clinical characteristics including toxicity grading and treatment course were analyzed in regarding to CT patterns. Clinical characteristics were compared between patients with ALK-IIP and without ALK-IIP.ALK-IIP was identified in 11 patients (4.4%). The most common CT pattern was the COP pattern (n = 7, 63.6%) and followed by HP and AIP patterns (both, n = 2, 18.2%). ALK-IIP showed pneumonitis toxicity grade ranged from 1 to 4, and AIP pattern had the highest toxicity grade, followed by HP and COP patterns (median grade: 3.5, 2.5, 1). All of the patients with the COP pattern were successfully treated, while half of patients with the AIP pattern died during treatment. The smoking history and extrathoracic metastasis were more frequent in patients with ALK-IIP (P < .005). The smoking history was associated with a higher incidence of ALK-IIP (odds ratio: 3.586, 95% confidence interval: 1.058-13.432, P = .049).ALK-IIP showed a spectrum of chest CT patterns, which reflected the toxicity grades. The COP pattern was the most common CT pattern of ALK-IIP, and patients with ALK-IIP of the COP pattern were successfully treated. ALK inhibitors should be used with caution in NSCLC patients with smoking history.

Weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer complicated by idiopathic interstitial pneumonias: a single-arm phase II study.

BACKGROUND: Idiopathic interstitial pneumonias (IIPs) are associated with increased risk of lung cancer. In Japan, acute exaberation of IIPs induced by anticancer treatment is a critical issue. For this reason, there is limited available evidence regarding the optimal treatment approach for lung cancer patients complicated with IIPs. Our previous prospective pilot study demonstrated the safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer (NSCLC) with IIPs. The current study was conducted to confirm the results of the same combination therapy used in a larger patient population. METHODS: Chemotherapy-naïve patients with advanced stage or post-operative recurrent NSCLC patients complicated by IIPs were enrolled. Patients received paclitaxel (100 mg/m2) on days 1, 8, and 15, and carboplatin (AUC 5.0) once every 4 weeks. RESULTS: Thirty-three of 35 enrolled patients were evaluable for analysis and received a median of four treatment cycles (range 1-6). Four patients (12.1%; 95% confidence interval 3.4-28.2%) had acute exacerbation (AEx)-related IIPs to the study treatment. However, no fatalities due to AEx were observed. The overall response was 69.7%. The median progression-free survival, median survival time, and 1-year survival were 6.3 months, 19.8 months, and 55.4%, respectively. CONCLUSIONS: The efficacy of carboplatin plus weekly paclitaxel treatment for advanced NSCLC patients with IIPs was comparable to that of conventional chemotherapy in advanced NSCLC patients without IIPs. Moreover, the primary endpoint was set to the frequency of treatment-related acute exacerbation, and the primary endpoint was met. These results suggest that patients with advanced NSCLC complicated by IIPs may benefit from this combination chemotherapy.

Acute Exacerbation of Idiopathic Interstitial Pneumonia in a Patient with Hepatocellular Carcinoma after Transcatheter Arterial Therapy Using Miriplatin.

A 76-year-old Japanese woman with recurrent hepatocellular carcinoma presented with acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) after transcatheter arterial therapy using miriplatin. She had a history of preexisting IIP five years before presenting at our hospital. On day 4 after transcatheter arterial therapy, she complained of shortness of breath. Subsequently, she developed acute respiratory failure on day 11 after transcatheter arterial therapy. Chest computed tomography revealed extensive ground-glass opacity and traction bronchiectasis in bilateral lung fields; subsequently, she was diagnosed with AE-IIP triggered by transcatheter arterial therapy using miriplatin. Despite systemic administration of high-dose corticosteroid and cyclophosphamide, she died of respiratory failure on day 36.

[Acute interstitial pneumonia in patient with rheumatoid arthritis treated with leflunomide]. / Ostre sródmiazszowe zapalenie pluc u chorego na reumatoidalne zapalenie stawów leczonego leflunomidem.

Leflunomide (LEF) is an isoxazole derivative used as disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA). It is effective and safe in patients with active RA, in whom standard treatment is insufficient or contraindicated, but it can cause interstitial lung disease (ILD). Identified risk factors for LEF-induced ILD include pre-existing ILD, cigarette smoking, low body weight, and use of loading dose. LEF should be avoided in patients with pre-existing ILD. We present a case of 59-year-old male with RA and a history of smoking and methotrexate (MTX) treatment, who developed dyspnoea, non-productive cough, and fever about two months after the administration of LEF. The clinical and radiological presentation was of acute pneumonia. The patient was treated with methylprednisolone pulse, prednisone, and cyclophosphamide, but he died of respiratory failure.

Smoking-related idiopathic interstitial pneumonia.

Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists 0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease.

Exacerbation of idiopathic interstitial pneumonias associated with lung cancer therapy.

OBJECTIVE AND METHODS: Idiopathic interstitial pneumonias (IIPs) frequently occur in association with lung cancer. However, there is no consensus on the best treatment of acute exacerbation of IIP in lung cancer patients (LC with IIP), including those with iatrogenic acute lung injury resulting from cancer treatments. We aimed to identify an appropriate strategy for treatment of this condition. We analyzed clinical features of 120 LC with IIP, retrospectively. RESULTS: The incidence of acute exacerbation related to anticancer treatment was 22.7%; when the incidence was examined separately for patients receiving chemotherapy or the best supportive care, the incidence was 20.0% and 31.3%, respectively. Additional investigations should be directed to finding suitable regimens for treatment of LC with IIP and the selection of appropriate patients with LC with IIP for chemotherapy. The incidence of acute exacerbation caused by combination regimens of carboplatin + paclitaxel or a platinum agent + etoposide was significantly lower than that of other regimens (0% vs. 18%, respectively; p=0.025, Fisher's Exact Test). Patients with high levels of C-reactive protein before chemotherapy had a significantly higher risk of developing acute exacerbation (odds ratio 5.60, p=0.028). CONCLUSION: There was no evidence that anticancer treatment, including chemotherapy, should be avoided in LC with IIP. To establish an appropriate cancer treatment for LC with IIP, a prospective clinical study should be performed to evaluate various treatment modalities in a larger patient population.