CSF-1-Targeted Therapies Continue to Redefine Systemic Treatment for TGCT
Key Clinical Takeaways:
- Key Outcomes: CSF-1/CSF-1R-targeted therapies demonstrate meaningful activity in TGCT; vimseltinib and pexidartinib show comparable response rates (~40%), with vimseltinib offering improved hepatic safety, and emerging agents showing promise for higher efficacy.
- Design/Population: Narrative review of literature published from 2005 to 2025 examining molecular pathogenesis, diagnosis, and systemic treatment of tenosynovial giant cell tumor, including approved and investigational CSF-1/CSF-1R inhibitors.
- Clinical Relevance: Systemic CSF-1R inhibition provides an effective option for patients with unresectable or recurrent TGCT, with safety and tolerability favoring newer agents and potentially shifting first-line treatment paradigms. Investigational agents such as pimicotinib and emactuzumab have shown encouraging activity, with early data suggesting potentially higher response rates and improved safety profiles.
According to a review of available literature, systemic CSF-1R inhibition demonstrates efficacy as a therapeutic option for patients with unresectable or recurrent tenosynovial giant cell tumor (TGCT), with safety and tolerability favoring newer agents and potentially shifting first-line treatment paradigms.
TGCT is a rare, locally aggressive neoplasm driven by overexpression of colony-stimulating factor 1 (CSF-1), leading to recruitment of CSF-1 receptor (CSF-1R)–positive macrophages and inflammatory cells that fuel tumor growth. Although surgical resection remains the standard initial approach, a substantial proportion of patients develop unresectable or recurrent disease associated with pain, functional impairment, and reduced quality of life, underscoring the need for effective systemic therapies.
A recent review of literature published between 2005 and 2025 highlights significant progress in understanding TGCT pathogenesis and the expanding role of systemic treatments targeting the CSF-1/CSF-1R axis. The review synthesizes data on diagnostic strategies and clinical outcomes associated with approved and investigational agents, with particular emphasis on CSF-1R inhibitors such as pexidartinib and vimseltinib, as well as emerging therapies in late-stage development such as pimicotinib and the monoclonal antibody emactuzumab.
Among currently available options, pexidartinib and vimseltinib demonstrate comparable clinical efficacy, with objective response rates of 39% and 40%, respectively, at 25 weeks. However, vimseltinib appears to offer a more favorable hepatic safety and tolerability profile, positioning it as a preferred first-line systemic therapy for patients with symptomatic, unresectable TGCT. Hepatotoxicity has been a key limitation of pexidartinib use in clinical practice, making safety considerations central to treatment selection.
Looking ahead, investigational agents such as pimicotinib and emactuzumab have shown encouraging activity, with early data suggesting potentially higher response rates and improved safety profiles. Ongoing and planned phase 3 trials will be critical in determining whether these therapies can further expand or refine the TGCT treatment landscape.
For clinicians managing TGCT, the growing availability of targeted systemic options marks an important shift away from repeated surgery alone, offering patients durable disease control with the potential for improved function and quality of life.
Source:
Conway A, Lim A, Schulte B, et al. Management of tenosynovial giant cell tumor: approved and investigational therapies. Expert Rev Anticancer Ther. Published online January 24, 2026. https://www.tandfonline.com/doi/full/10.1080/14737140.2026.2620510#abstract
