(1172) Fatal Case of Alectinib-Induced Pneumonitis

Introduction: Pneumonitis is a known complication of anticancer agents that are known to cause diffuse interstitial lung disease and pulmonary fibrosis. Alectinib is a tyrosine kinase inhibitor of the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor. It is highly selective and used to treat advanced non-small cell lung cancer. We present a rare fatal case of Alectinib induced pneumonitis (AP).

Description: A 70-year-old female with metastatic ALK-positive lung adenocarcinoma on Alectinib and stage III chronic kidney disease (CKD) presented with confusion and dyspnea. Initial chest x-ray revealed pneumonitis of the right upper and lower lobes. CT angiography of the chest showed diffuse ground-glass opacities with peribronchial consolidations. Alecitinib was discontinued, empiric antibiotics were started, and she was admitted for management of acute hypoxemic respiratory failure. Due to worsening respiratory status, she was transferred to the intensive care unit (ICU) for respiratory failure secondary to pneumonitis and concerns for ARDS. She was started on dexamethasone 20 mg for 5 days followed by 10 mg for 5 days and diuretics without clinical improvement. She was then initiated on methylprednisolone 1 g daily for 3 days followed by 60 mg twice daily. She received 1 dose of weight-based infliximab at this point in her treatment. Sadly, the hypoxemia persisted and she required alternating BPAP (non-invasive ventilation) and high flow nasal cannula support throughout her ICU course. Follow-up chest x-rays revealed fibrotic changes. Despite aggressive medical treatment, she succumbed to her illness.

Discussion: AP is a rare complication, but it has been documented in case reports. These reported cases of AP resolved once it was discontinued. A study review of 56 patients receiving Alectinib found that patients over the age of with impaired renal function were at increased risk for pneumonitis. Our patient was initiated on Alectinib 9 months prior with known CKD. Little data exist regarding prevalence and mortality of AP. To our knowledge there are no documented fatal cases. This case highlights the severity of AP in patients with impaired renal function and advanced age. Providers should be cautious in prescribing to high-risk patients.