Pembrolizumab Activity in Tyrosine Kinase Inhibitor–Refractory Metastatic
GIST
: A Case Report
Neharika Bandaru, Job Shiach, Mark Agulnik ABSTRACT
Introduction
Gastrointestinal stromal tumors (GISTs) are commonly driven by activating mutations in KIT or PDGFRA . Although sequential tyrosine kinase inhibitors (TKIs) have improved outcomes in advanced disease, acquired resistance is common. Prospective studies of immune checkpoint blockade in GIST have shown limited activity, and immunotherapy is not a standard treatment.
Case Presentation
A man diagnosed at age 57 with epithelioid small‐bowel GIST developed hepatic metastatic disease 7 years after his initial diagnosis. His tumor harbored a primary KIT exon 11 D579del mutation, a secondary KIT exon 17 D820G mutation, and CDKN2A/CDKN2B deletions; available molecular testing reported a low tumor mutational burden (1 mutation/Mb) and microsatellite‐stable disease. After progression or treatment‐limiting toxicity during six TKI regimens, pembrolizumab was initiated on October 28, 2025, when he was 76 years old, and administered intravenously every 3 weeks. The treatment has demonstrated stable disease on CT imaging; cycle 13 was then administered on July 28, 2026. No treatment delays or treatment‐related adverse events were reported through cycle 13.
Conclusion
Pembrolizumab was associated with at least 9 months of disease control in TMB‐low, microsatellite‐stable metastatic GIST after six TKI regimens. Because contemporaneous immune profiling and complete historical dosing data were unavailable, this observation is hypothesis‐generating and does not establish that prior TKI exposure sensitized the tumor to PD‐1 blockade.