Supplementary Material for: Objective Responses in Metastatic Pleomorphic Rhabdomyosarcoma Treated with Combination of Doxorubicin and Pembrolizumab

Introduction
Pleomorphic rhabdomyosarcoma is a rare sub-type of rhabdomyosarcoma, a soft-tissue sarcoma that originates from skeletal myoblast cells. Although rhabdomyosarcomas are typically seen in the pediatric population, the pleomorphic variant often presents in adulthood, and is characteristically aggressive with no currently established treatment regimen in the setting of metastatic disease. There has been growing interest in the application of immune checkpoint inhibitors alongside conventional chemotherapeutic agents in the treatment of pleomorphic rhabdomyosarcoma.

Case Presentations
In the present case series we report two patients with metastatic pleomorphic rhabdomyosarcoma treated with combination doxorubicin and pembrolizumab who had confirmed objective responses. Of note, these two patients had variable PD-L1 status - negative, and low positive. Duration of treatment response was notable at 14 months and 9 months respectively, with the first patient remaining on maintenance pembrolizumab therapy, and the second patient subsequently achieving complete response with third-line trabectedin. Both patients are currently undergoing routine interval imaging with no evidence of disease at this time.

Conclusion
This report highlights and discusses the potential role of PD-1 blockade in the treatment of pleomorphic rhabdomyosarcoma, and also discusses burgeoning immunological data that may explain the clinical responses seen in these two cases.