Microsatellite stability and mismatch repair proficiency in nasopharyngeal carcinoma may not predict programmed death-1 blockade resistance

The US FDA granted accelerated approval to pembrolizumab for microsatellite instability-high and mismatch repair deficient cancers. The response of programmed death-1 blockade in mismatch repair proficiency (pMMR) colorectal cancer is very poor, however, whether such treatment is effective in pMMR nasopharyngeal carcinoma (NPC) remains unknown. We report a case of a 51-year-old man with NPC. PET-CT scan revealed a space-occupying lesion in the left lung, and the pathologic result confirmed the occupying lesion originated from NPC. Meanwhile, both immunohistochemistry and PCR revealed that the occupying lesion belonged to pMMR NPC. The lung lesions largely shrunk after chemoradiotherapy. One year later, MRI showed brain occupancy, and brain lesion resection surgery was performed subsequently. The resected tissue was also validated to be the metastatic lesion from NPC. After one month, the patient was examined again by PET-CT, which showed multiple metastases in the liver, pelvis and adrenal gland. Since January 2017, the patient has been treated with pembrolizumab therapy. After five courses of treatment, both PET-CT and blood testing were repeated and demonstrated that metastases and serum Epstein-Barr virus DNA almost completely disappeared. We provide the first report that pembrolizumab has a confirmed objective response to microsatellite stability and pMMR NPC, and two biomarkers may not be sufficient to identify patients who might be resistant to such treatment in NPC.