Acute interstitial lung disease in a patient with anaplastic lymphoma kinase-positive non-small-cell lung cancer after crizotinib therapy

Abstract

Crizotinib, an orally active multi-targeted small-molecule anaplastic lymphoma kinase (ALK) inhibitor, is an effective treatment modality for advanced ALK-positive non-small-cell lung cancer (NSCLC). Most drug-related adverse events are mild to moderate; however, some patients may develop acute interstitial lung disease (ILD) which is sometimes fatal. We present a case of crizotinib-associated ILD in a 47-year-old woman treated with crizotinib for metastatic adenocarcinoma of the lung. The patient presented with acute breathlessness and hypoxaemia in the second month of crizotinib therapy; radiological and histopathological work-up was suggestive of acute interstitial pneumonia. The patient improved clinically with corticosteroid therapy and was successfully re-challenged with crizotinib. In conclusion, while treating NSCLC patients with crizotinib, it is important to promptly investigate and treat any new-onset respiratory symptoms, as the latter could represent an adverse effect related to therapy. Prompt discontinuation of the offending drug and initiation of corticosteroid therapy may prevent adverse outcomes.

Crizotinib Associated with Ground-Glass Opacity Predominant Pattern Interstitial Lung Disease: A Retrospective Observational Cohort Study with a Systematic Literature Review

“…After a systematic review of the literature, we identified 43 other cases of crizotinib-associated ILD, among which 34 were notified in the PROFILE studies and nine case reports described in more detail [10][11][12][13][14][15][16][17][18] (Table 3).…”

“…Other reported cases had few symptoms like ours (Table 3). 14,16,17 Crizotinib was restarted with corticosteroids, 12,16,17 except in one case. 14 This latter being the only which presented a relapse.…”

Interstitial Lung Disease Induced by Crizotinib in Non-Small-Cell Lung Cancer

“…Crizotinibinduced ILD is considered a rare event, 6 however, nowadays, there are more cases of Crizotinib-induced ILD reported, most of them in Asian patients with no related smoking exposure. 1,[7][8][9][10][11][12] Cough, fever and dyspnea may be present in patients with advanced NSCLC treated with TKIs, like in our case, but are usually non-specific. 3 In addition, the onset of pulmonary complications is unpredictable and there have been some life-threatening cases.…”

The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions

“…There was one grade 5 adverse event in the PROFILE 1014 trial, which was attributed to crizotinib-associated pneumonitis. Pneumonitis/interstitial lung disease of any grade is seen in approximately 2.5% of patients treated with crizotinib [19]. …”