Management of tenosynovial giant cell tumor: approved and investigational therapies

INTRODUCTION: Tenosynovial giant cell tumor (TGCT) is a rare, benign neoplasm driven by overexpression of colony-stimulating factor 1 (CSF-1), which recruits CSF-1 receptor (CSF-1 R)-bearing macrophages and other inflammatory cells to promote tumor formation. While surgery remains the first-line treatment for TGCT, many patients experience unresectable or recurrent disease with high morbidity, highlighting the need for effective systemic treatments. AREAS COVERED: This review summarizes the molecular pathogenesis, diagnostic approach, and evolving systemic treatment landscape for TGCT, with a focus on treatments directed at CSF-1/CSF-1 R inhibition. Relevant literature published between 2005 and 2025 was identified through PubMed searches and manual review of reference lists. Clinical efficacy and safety data for approved and investigational CSF-1/CSF-1 R inhibitors, including pexidartinib, vimseltinib, and emerging agents, are discussed. EXPERT OPINION: Pexidartinib and vimseltinib demonstrate comparable efficacy in TGCT with objective response rates (ORR) of 39% and 40%, respectively, at week 25 of treatment; however, vimseltinib offers improved hepatic safety and tolerability, supporting its use as the preferred first-line systemic therapy. Emerging agents, including pimicotinib and emactuzumab, show potential for higher response rates and favorable safety profiles and may further reshape the TGCT treatment paradigm pending phase 3 trial results.