S4213 Advanced Esophageal Cancer Treated by Immune Checkpoint Inhibitors Combination Therapy With Fatal irAEs and Complete Response: Case Report

Introduction: Cancer immunotherapy using immune checkpoint inhibitors (ICIs) has become a new treatment modality in cancer chemotherapy in the 2010s, and is now widely approved for many types of cancer. The first approved ICI combination in Japan consists of Nivolumab, an anti-PD-1 antibody, and Ipilimumab, an anti-CTLA-4 antibody. ln the combination therapy, ipilimumab is administered at different doses, intervals, and frequencies depending on the cancer type. ICIs combination therapy has been reported to be more effective than ICI monotherapy, but also, be associated with more severe adverse events. Case Description/Methods: The patient was a 74-year-old man who complained of dysphagia and thus was admitted to our hospital. He was diagnosed to have an advanced thoracic esophageal carcinoma lesion (Im-Ei) with multiple lung metastasis and lymph nodes. We thus diagnosed the patient to have advanced carcinoma with any metastasis and therefore chemotherapy was done first. He has severe renal dysfunction (eGFR 36.6) was treated by combination chemotherapy, consisting of Nivolumab and Ipilimumab. After 2 cycles, the patient experienced severe dyspnea. Because the patient was in a critical condition, treatment had to be discontinued. After treatment for the lung damage, a computed tomography scan was performed and it was found that the lesions had disappeared, even though chemotherapy had not been administered. The chemotherapy proved to be very effective. Drug-induced lung damaged made it difficult to continue. However, 2-years follow-up was done with computed tomography; the lesions continued to disappear. The patient is still alive. Discussion: In previous reports, higher efficacy of ICI combined therapy was expected in cases with irAEs, and there were cases with long-lasting efficacy even after early discontinuation of ICIs due to irAEs. In this case, the meaningful and durable response to ICIs in the current of esophagus cancer although the treatment period was short (2 cycles) by CTCAE Grade 3 or higher for severe irAEs. Another distinctive feature of this case is that the lesions continued to disappear. The meaningful and durable clinical response to ICIs in the current case of cancer suggests the utility and severe risk of immunotherapy in cancer. We report our findings in conjunction with other cases with irAE.