Case Report An Exceptional Responder to Nivolumab in Metastatic Non-Small-Cell Lung Cancer: A Case Report and Literature Review of Long-Term Survivors Babak Baseri , 1 Bachar Samra, 1 Eric Tam , 1 Edwin Chiu , 1 and Andrea Leaf 1,2 1 Department of Hematology/Oncology, State University of New York Downstate Medical Center, Brooklyn, New York, USA 2 Department of Hematology/Oncology, Veterans Affairs New York Harbor Healthcare System, Brooklyn Campus, New York, USA Correspondence should be addressed to Babak Baseri; bbaseri.82@gmail.com Received 9 September 2019; Accepted 4 November 2019; Published 5 December 2019 Academic Editor: Constantine Gennatas Copyright © 2019 Babak Baseri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Exceptional responders to immune checkpoint inhibitors in metastatic non-small-cell lung cancer (NSCLC) are rare. Furthermore, the optimal duration of immunotherapy in patients who achieve complete remission and the benefit of rechallenge after recurrence remain unknown. Studying the clinical course of exceptional responders can help identify potential predictors of response to immunotherapy and further fine-tune our management algorithms in the absence of standard of care in challenging scenarios. Case Presentation. We highlight the case of a 73-year-old Vietnam War Veteran with active tobacco dependence who achieved complete response with nivolumab for metastatic NSCLC after four prior lines of chemotherapy. Nivolumab was discontinued after 10 cycles due to immune-mediated hepatitis that resolved with steroids. He remained in complete remission for 14 months while off therapy. Then, his tumor recurred twice locally in the mediastinum and he again achieved complete and durable responses after each recurrence with radiotherapy. Due to recurrence in both lungs one year later, he was rechallenged with nivolumab and achieved partial response after two months of therapy. He continues to do well five and a half years since his initial diagnosis of de novo metastatic NSCLC. Conclusion. Optimal management of exceptional responders to immune checkpoint inhibitors in metastatic NSCLC is largely unknown. Our case report adds to the limited data supporting the use of localized therapy for oligometastatic recurrences and rechallenge with immunotherapy for widespread disease in achieving disease control and long-term survival. 1. Introduction The use of immune checkpoint inhibitors (ICI) in many malignancies including non-small-cell lung cancer (NSCLC) has revolutionized the field of oncology and has magnified the critical role of the immune system in fighting cancer [1, 2]. However, only a select group of patients derive clin- ically meaningful benefit from immunotherapy, ranging from improved quality of life to durable clinical responses, including rare complete remissions that may last many months even beyond immunotherapy discontinuation [3, 4]. The superior efficacy of immunotherapy in such exceptional responders has sparked an intense research interest in can- cer immunobiology [1, 5]. Here, we describe the clinical course of a patient with heavily pretreated NSCLC who had an exceptional response to a short treatment course with nivolumab. 2. Case Presentation A 73-year-old Vietnam War Veteran with active tobacco dependence (1:5 - 2 packs per day > 50 years), prostate can- cer in remission (status post definitive radiation in 2008), and alcoholic fatty liver disease was diagnosed in November 2013 with metastatic poorly differentiated lung adenocarci- noma of the left upper lobe (LUL) with biopsy-proven pleu- ral and pericardial metastases after he presented with pneumonia and lung nodules. Molecular studies were nega- tive for EGFR mutation and ALK rearrangement, and non- diagnostic for ROS-1. Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 1816472, 7 pages https://doi.org/10.1155/2019/1816472