Pembrolizumab for MSI-high/TMB-high bone and soft tissue sarcomas: a retrospective single-institution study

Bone and soft tissue sarcomas are rare, heterogeneous malignancies with limited treatment options for advanced stages. Pembrolizumab, an anti-PD-1 immune checkpoint inhibitor (ICI), is approved for tumors exhibiting high microsatellite instability (MSI-high) or high tumor mutation burden (TMB-high); however, its efficacy remains unclear.

We reviewed records of 40 patients with advanced/recurrent sarcoma who underwent genomic profiling. MSI status and TMB were assessed using the NCC Oncopanel^® or FoundationOne^®. Patients identified as MSI-high and/or TMB-high received pembrolizumab (200 mg/body weight every 3 weeks). Clinical outcomes were evaluated using RECIST v1.1 and adverse events graded per CTCAE v5.0.

Three patients (7.5%) were MSI-high and/or TMB-high: one each with undifferentiated pleomorphic bone sarcoma, leiomyosarcoma, and dedifferentiated chondrosarcoma. All had metastatic disease and received chemotherapy. Pembrolizumab was administered for 5-25 cycles for 5-18 months. Two patients achieved a partial response, and one had stable disease, yielding an objective response rate of 67% and a mean response duration of 12.7 months. No complete response or disease progression occurred. The adverse events were limited to grade 2 thyroid dysfunction and skin toxicity. No grade ≥3 events or treatment discontinuations occurred.

Pembrolizumab demonstrated promising efficacy and tolerability in MSI-high/TMB-high sarcomas. These findings support biomarker-driven immunotherapy in patients with sarcomas. Comprehensive genomic profiling should be considered in refractory cases. Further studies are warranted to validate these results and explore additional biomarkers.