Capmatinib-induced interstitial lung disease: A case report

Abstract

Unstructured abstract: Capmatinib, a highly specific MET inhibitor, was recently approved by the FDA for use in MET exon 14 skipping mutation-positive NSCLC. Although it is usually well tolerated, we describe the first case of a patient who incurred severe pneumonitis linked to this treatment.A 76 year-old-man with a 20 pack-year exposure was diagnosed with metastatic lung adenocarcinoma with a PD-L1 status of 90% and started on pembrolizumab. After two cycles, disease progressed and a secondary NGS panel found a MET exon 14 skipping mutation, prompting a switch to capmatinib. After one month of capmatinib, CT showed diffuse partial tumoral response but areas of organizing pneumonia (OP) appeared in both lungs, with severe respiratory symptoms. Capmatinib was suspended and high dose systemic steroids were administered, allowing for a rapid improvement in OP lesions and symptoms. At five months, because of cerebral disease flare-up, oncological treatment was resumed by crizotinib, with diffuse tumoral response on subsequent evaluations and no recurrence of lung toxicity.This is the first reported case of capmatinib-induced pneumonitis. The general management of TKI-induced pneumonitis (treatment suspension +/- systemic steroids) was applied successfully in this patient. Close proximity of capmatinib initiation to a previous immune checkpoint-inhibitor treatment might have contributed to lung injury. The mutational diagnostic delay was especially clinically relevant in this case, considering the poor sensitivity of MET-driven NSCLC to immunotherapy.

Keywords

• NSCLC
• Targeted therapy
• Driver oncogene