Clinical characteristics and risk factors of drug‐induced lung injury by ALK tyrosine kinase inhibitors: A single center retrospective analysis

Abstract

Background: If anaplastic lymphoma kinase (ALK) gene rearrangement in lung cancer is identified, ALK-tyrosine kinase inhibitors (ALK-TKIs) can be an effective treatment. However, the details of drug-induced lung injury (DILI) caused by ALK-TKI, which can be a serious side effect of ALK-TKIs, remains unclear. This study aimed to investigate the clinical features and the onset risk factors of DILI by ALK-TKIs in clinical practice. Methods: The clinical features of 56 consecutive patients who received crizotinib, alectinib, and/or ceritinib at our hospital from 2012 to 2018 were retrospectively examined. Among these, patients diagnosed with DILI due to ALK-TKIs were evaluated in terms of clinical features and parameters. Each clinical parameter before the administration of ALK-TKIs was compared between the DILI onset group and the non-onset group. Results: A total of seven cases were diagnosed with DILI due to ALK-TKIs; no DILI-related deaths were observed. Chest computed tomography (CT) scan findings identified six patients with the organizing pneumonia (OP) pattern and one with the hypersensitivity pneumonia pattern. The onset of DILI was significantly different in patients age ≥ 64 years and with a creatinine clearance <80 mL/ minute. Conclusions: Extra caution for DILI due to ALK-TKIs may be needed when recommending ALK-TKIs for patients over 64 years of age, or with decreased renal function. CT images of the majority of patients with DILI by ALK-TKIs show an OP pattern. Key points• Significant findings of the study: Extra caution is needed when recommending ALK-TKIs for patients over 64 years of age or those with decreased renal function. Computed tomography images of the majority of patients with DILI by ALK-TKIs show an OP pattern. • What this study adds: The same or a different ALK-TKI may be considered as a treatment option after the onset of DILI, based on careful judgment.

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

“…Its molecular targeting, high specificity, targeted drugs, without blood and neurotoxicity and other characteristics, greatly improve the quality of life of patients [ 115 ]. Several clinical drugs have been developed [ 116 , 117 , 118 ], such as the inhibition of epidermal factor receptor (EGFR) [ 119 ], anaplastic lymphoma kinase (ALK) and ROS1, etc. Currently, several new treatment combinations and new drugs are being investigated.…”

Lung Cancer and COVID-19: Therapeutic Implications

“…Accordingly, the incidence of Interstitial lung disease (ILD) in Asian patients from the J-ALEX study was 8%, while in non-Asian patients from the ALEX study ILD was 1% [50,51]. The pattern of pulmonaryinvolvement, secondary to ALK-TKIs, is usually organized pneumonia with generally good response to corticosteroids [52]. The timing of toxicity presentation does not help in the differential diagnosis of COVID-19, as it can occur from a few days to several months after treatment initiation, with the exception of Brigatinib, for which some studies have reported few cases of early toxicity within the first 7 days of treatment [51][52][53].…”

“…The pattern of pulmonaryinvolvement, secondary to ALK-TKIs, is usually organized pneumonia with generally good response to corticosteroids [52]. The timing of toxicity presentation does not help in the differential diagnosis of COVID-19, as it can occur from a few days to several months after treatment initiation, with the exception of Brigatinib, for which some studies have reported few cases of early toxicity within the first 7 days of treatment [51][52][53]. ILD is more frequent in smokers and has been associated to renal function reduction, older age, and previous pleural effusion [54].…”

Characteristics and risk factors for drug-induced lung injury in hospitalized patients: A matched case-control study

“…In addition, identifying speci c drugs with potential risks for each patient with DLI is also challenging. Previous studies have suggested that age, gender, smoking, pulmonary surgery, thoracic radiotherapy, chemotherapy, diabetes, hypoproteinemia, and pre-existing lung disease might be risk factors for DLI [7][8][9][10][11] . However, the information about DLI in clinical practice is still limited, and the clinical features and pathogenetic factors of DLI are not fully clear.…”