Hyperprogressive Disease in an Advanced Stage Colon Cancer Patient on Pembrolizumab: A Case Report

The emergence of immune checkpoint inhibitors (ICIs) in recent years has transformed the landscape of the management of solid tumors. The advancement of immunotherapy has resulted in a brand new set of adverse outcomes not previously seen in classical chemotherapy. One such adverse effect has been termed as hyperprogressive disease (HPD), a phenomenon characterized by rapid tumor progression, which often leads to devastating outcomes. In this report, we present a unique case of a 48-year-old African American female who initially presented with abdominal pain, fatigue, and weight loss. Subsequent CT scan showed extensive irregular wall and luminal narrowing with an eccentric mass and adenopathy along the portacaval space. Tumor markers were found to be elevated and genetic testing was done. The patient was diagnosed with stage IIIC colon cancer with K-RAS wild type, associated with Lynch syndrome. The patient underwent surgical resection, chemotherapy, and targeted therapy for progressive/stage IV disease. In light of the progression of the disease, pembrolizumab was introduced into the treatment regimen. One month after the treatment, a repeat CT scan showed enlargement of the metastatic lesion with almost double the size. The progression of the disease was so rapid and, ultimately, pembrolizumab administration was withheld and the patient passed away after about two months on pembrolizumab. To our knowledge, this is one of the few cases of HPD reported in patients with advanced colon cancer, particularly in one with Lynch syndrome. Further studies are warranted to understand why some individuals benefit from immunotherapy, whereas others experience grave outcomes.