Response And Oligoclonal Resistance To Pembrolizumab In Uterine Leiomyosarcoma: Genomic, Neoantigen, And Immunohistochemical Evaluation.

11043Background: Predictive biomarkers for response and resistance to immune checkpoint blockade targeting programmed death 1 (PD-1) are incompletely characterized, and the utility of anti-PD-1 therapy for uterine leiomyosarcoma (ULMS) is unknown. Methods: A 49 yo woman with ULMS developed rapidly progressive metastatic disease 4 months after R1-resection of the primary tumor and was enrolled on a phase 1b study of pembrolizumab (10 mg/kg every 2 wks) (KEYNOTE-028). Tumor regression at multiple metastatic sites occurred within 2 months. A single pre-existing metastasis increased in size and was resected at 9 months. IHC, whole exome/transcriptome sequencing, and neoantigen analysis was performed on primary pretreatment (preRx) and treatment-resistant tumors (postRx). Results: Responsive tumor sites revealed complete pathologic response at time of surgery. Progressive tumor demonstrated viable ULMS. IHC showed tumor cells negative for PD-L1 and positive for PD-L2 both preRx and postRx. Degree of PD-1+ lymp...