BACKGROUND Pancreatic
adenocarcinoma (PDA) is associated with an 8.6-fold increased risk in
Lynch syndrome patients. Here, we report the case of a
Lynch syndrome PDA patient with an exceptional response to a single cycle of
pembrolizumab immunotherapy. CASE REPORT A 65-year-old male patient with
Lynch syndrome mismatch repair (MMR) deficient PDA with metastatic
liver disease, received 1 cycle of
pembrolizumab (200 mg) after progressing on 2 standard lines of treatment. His initial computed tomography (CT) showed 3×2.5 cm PDA. At that time, the disease was considered borderline resectable, and the patient received 6 cycles of
FOLFIRINOX followed by
chemoradiotherapy with
capecitabine. A follow-up CT scan showed multiple new liver lesions. The biopsy showed metastatic PDA and
tumor tissue demonstrated high
microsatellite instability with abnormal/lost expression of MLH1 and PMS2
proteins. The patient was started on
pembrolizumab. Only 1 cycle was given due to the development of thromboembolic complications:
pulmonary embolism and
myocardial infarction. His
thrombophilia workup was negative. Restaging CT scans at 3, 6, and 9 months after 1 cycle of
pembrolizumab revealed an excellent response with shrinkage of liver lesions. Restaging at 11 months showed the eventual resolution of most liver lesions. No new metastatic disease developed. A repeat biopsy of the dominant liver lesion showed no morphological evidence of PDA. CONCLUSIONS Only 1 cycle of
pembrolizumab resulted in clinical complete response and pathologic response in metastatic PDA. We emphasize the importance of testing for MMR status and treating with
immunotherapy in metastatic PDA patients with
MMR deficiency.