Unexpected Durable Complete Response With Anti–PD-L1 Blockade in Metastatic Undifferentiated Pleomorphic Sarcoma: A Case Report With Host and Tumor Biomarker Analysis

Abstract

Soft-tissue sarcomas (STSs) are a heterogeneous group of tumors, representing approximately 1% of adult malignancies.1 Within STSs, undifferentiated pleomorphic sarcomas (UPSs) are one of the most frequent subgroups (5%-15%).2 Treatment options of advanced UPS remain limited, and the prognosis of patients with metastatic disease is poor, with a median survival of approximately 12 months.3 UPS is characterized by a high level of genomic instability, as indicated by its complex karyotype with low tumor mutational burden (TMB) but high copy number alterations.4,5 This feature can be theoretically associated with higher immunogenicity because of a potential increase in neoantigen formation.6 For this reason, there is potential role for immunotherapy with immune checkpoint inhibitors (ICIs) in this subset of patients.7 Here, we report the case of a patient with metastatic UPS of the chest wall successfully treated with an anti–PD-L1 ICI at the Clinical Trial Unit of the Hospital Clinic of Barcelona (HCB), who experienced an exceptionally prolonged complete response (CR). Because of the lack of biomarkers for the correct identification of patients with UPS benefiting the most from ICIs, an extensive clinicopathological and molecular profiling was performed to explain this uncommon response