Phase 2 trial of nivolumab for prevention of oral squamous carcinoma in high-risk oral leukplakia patients

Proliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC). A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing a rationale to investigate immune checkpoint therapy. A phase 2 trial at Dana-Farber Cancer Institute (Boston, MA) evaluated nivolumab in high-risk PVL patients. The trial found variable lesion regression by size and degree of dysplasia in reponse to therapy, while 27% of patients developed invasive oral cancer after nivolumab. All whole-exome sequenced patients who progressed to develop cancer had 9p21.3 chromosomal loss. The authors conclude that nivolumab showed potential clinical activity for high-risk oral precancerous disease.