Rapid Onset of Acute Respiratory Failure Due to Crizotinib-Induced Pneumonitis

Abstract

Introduction: Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor used for advanced ALK-positive nonsmall cell lung cancer. It can rarely cause interstitial lung disease with a wide range of presentations from asymptomatic pulmonary radiological findings to fatal pneumonitis. Here, we present a case of rapid, acute hypoxemic respiratory failure due to crizotinib-induced pneumonitis. Case presentation: A 63-year-old man with a medical history of head and neck squamous cell cancer with metastasis to pulmonary parenchyma, pleura and mediastinal lymph nodes presented with dyspnea, fever and non-massive hemoptysis four days after initiation of crizotinib therapy. The patient was febrile, tachycardic, tachypneic and hypoxemic upon presentation. Laboratory investigations were unremarkable. Respiratory viral panel and reverse transcription-polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 were negative. Further investigations including sputum, blood and urine culture were unrevealing. Chest radiographs rapidly progressed from baseline imaging to scattered patchy multifocal infiltrates. One day later, computerized tomography of the chest revealed rapidly progressing diffuse bilateral ground glass opacities. Despite empiric anti-microbial therapy, the patient's respiratory status deteriorated, and he was transferred to medical intensive care unit. He was pulsed with IV methylprednisolone 500mg twice a day for 3 days, followed by a slow taper for presumed pneumonitis secondary to crizotinib which led to a rapid improvement in his respiratory status. Discussion: ALK inhibitors are a relatively novel therapy for several malignancies and the side effects are not well known. In clinical trials, crizotinib was associated with interstitial lung disease in 2.4% of cases and presented at a median time of 20 days to 2 months after initiation. Management is challenging because there are no guidelines currently available for diagnosis and treatment of ALK inhibitor associated pneumonitis. Diagnosis generally requires a recent history of drug exposure, abnormal thoracic radiography, and clinical and/or radiologic improvement after discontinuation of the offending agent. Given their increasing use to treat various malignancies, it is imperative for clinicians to have a high index of suspicion for crizotinib-induced pneumonitis. A multidisciplinary approach will lead to rapid diagnosis and early treatment of this serious adverse events associated with this novel drug.