S3750 The Disappearing Act: Single Agent Pembrolizumab-Induced Remission of Microsatellite Stable Colon Adenocarcinoma

Introduction: In 2014, Pembrolizumab, a PD-1 inhibitor, was approved by the FDA. PD-L1 is found on tumor cells secondary to mutations in signaling pathways. Induction of PD-L1 by malignancies can have an immunosuppressive effect, allowing evasion of cytotoxic T cell-mediated immune response. Pembrolizumab blocks attenuation of T cell-mediated response by binding PD-1 to prevent binding to PD-L1 of malignant cells. Pembrolizumab has FDA approved indications microsatellite instability-high (MSI-H) colorectal cancer (CRC). MSI-H CRC has unique behavior compared to microsatellite stable (MSS) tumors involving defects in mismatch repair (MMR) enzymes and a resulting higher tumor mutational burden (TMB) that allows for efficacy of PD-1 inhibitors. This efficacy is not seen in the setting of MSS CRC. Case Description/Methods: We present the case of a 73-year-old man admitted for acute hypoxic respiratory failure and found to have left lung atelectasis secondary to a hilar mass invading the left main bronchus. Bronchoscopy showed a poorly differentiated Stage 3B Non-Small Cell Carcinoma with PD-L1 expression of 100%. Positron emission tomography scan showed the known lung primary and disease in mediastinal lymph nodes and distal transverse colon. Colonoscopy showed a 6 cm transverse colon mass which was biopsied and tattooed. Pathology showed poorly differentiated MSS colon adenocarcinoma. Treatment of the lung malignancy was prioritized. He started Pembrolizumab and computed tomography (CT) thorax after 10 cycles showed good response to immunotherapy with resolution of hilar mass and significant decrease in mediastinal lymphadenopathy. Repeat colonoscopy did not find any mass at the tattooed site. Colonoscopy done 2 years later continued to show absence of tumor. He completed 2 years of immunotherapy with Pembrolizumab (17 cycles) and is currently managed with surveillance scans every 3 months and colonoscopy annually for a total of 5 years post detection. Discussion: Colorectal cancers with high levels of MSS are marked by a high tumor mutational burden that evokes a strong immune response with corresponding expression of PD-L1 by these cancers to negatively modulate this immune response. CRC's with high MSI are responsive to PD-1 inhibiting agents like pembrolizumab while MSS CRC's have a lower tumor mutational burden and evoke less of an immune response so they are less responsive to these agents. We aim to draw attention to the possibility of PD-1 inhibitor use in management of MSS cancers and highlighting the need for additional study of this topic.