A CHECK POINT INHIBITOR-RELATED FATAL TOXICITY

Abstract

SESSION TITLE: Medical Student/Resident Lung Pathology 3 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD-1) improve the hosts antitumor immune response and have demonstrated tremendous promise in the treatment of certain malignancies. Recently, there are emerging reports of serious autoimmune related toxicities from immune checkpoint blockade therapy. In our practice, we have encountered a fatal immune related adverse event on a patient who was treated with pembrolizumab. CASE PRESENTATION: 74 year old male with biopsy proven stage IV squamous cell esophageal cancer with metastasis to the lung presented to our service with a upper respiratory infection and cough with rusty colored sputum. He had been treated with pembrolizumab 3 days prior to the patient’s presentation. On examination, the patient was found to be hypoxemic on room air, tachycardic, and tachypneic. Initial chest film showed diffuse interstitial infiltrates; CT angiography of the chest elucidated significant new diffuse ground-glass infiltrates. The patient was initially treated for a suspected acute infectious pneumonia requiring high levels of noninvasive oxygen supplementation. Due to the lack of other etiologies such as environmental, infectious, and occupational, it was determined by pulmonology that this was most likely an adverse effect of the patient’s immunotherapy. The imaging studies were similar to previously seen pembrolizumab induced auto-immune pneumonitis. In accordance with both the pulmonology and oncology services, the patient was treated with high dose systemic steroids. Despite this, the dyspnea worsened and the patient declined mechanical ventilation. Eventually, he succumbed to the sequelae of pembrolizumab related auto-immune grade IV pneumonitis causing respiratory failure and cardiac arrest. DISCUSSION: The overall use of check-point inhibitors (CPIs) has increased survival in patients with certain types of cancer. While serious toxicities have been described in the literature from CPI therapy there are limited case reports describing auto-immune adverse effects such as vitilgo, auto-immune encephalitis, and auto-immune pneumonitis. In our review of previous literature, we found that there have only been several reported cases of auto-immune pneumonitis. In our case, there was a direct correlation between pembrolizumab and the development of grade IV auto-immune pneumonitis causing acute respiratory failure and death. CONCLUSIONS: There is a known relationship in the development of autoimmune toxicities in patients receiving checkpoint inhibitors. Clinicians need to have a high index of suspicion for high grade intestinal pneumonitis when patients treated with CPIs present with respiratory symptoms. It behooves us to further educate ourselves and direct therapy accordingly. These results encourage future Randomized Controlled trials (RCTs) to follow the efficacy and long-term side effects of these new therapies. Reference #1: Nishino, M. (2016). Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis. JAMA Oncology, 12. doi:10.1001 Reference #2: Nishino, M. (2016). PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course. Clinical Cancer Research, 24. doi:10.1158 Reference #3: Chuzi, S. (2017). Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor-related pneumonitis. Cancer Management Research, 9. doi:10.2147 DISCLOSURES: No relevant relationships by Nemer Dabage, source=Web Response No relevant relationships by Ian Kahane, source=Web Response No relevant relationships by fiorella pendola, source=Web Response No relevant relationships by Vijay Srinivasan, source=Web Response