Long‑term safety of CSF‑1R inhibitors in TGCT

By Laura Boyd

Two safety analyses evaluating longer-term treatment with colony–stimulating factor  1 receptor (CSF-1R) inhibitors in tenosynovial giant cell tumor (TGCT) were presented at the ESMO Sarcoma and Rare Cancers Congress 2026.

Across both datasets, the authors reported that CSF-1R inhibition was associated with largely manageable adverse events (AEs) over extended treatment durations, with no evidence of new or cumulative safety signals emerging over time.

In extended analyses from the phase 3 MANEUVER trial, Hans Gelderblom (Leiden University Medical Center, Netherlands) and colleagues reported detailed findings on the incidence, timing, and resolution of AEs of clinical interest (AECIs) in patients treated with the highly selective CSF-1R inhibitor pimicotinib.

In MANEUVER, 63 patients randomized to pimicotinib were followed for a median of 14.3 months, with a median treatment exposure of 14.2  months. The most common any-grade AECIs were elevated blood creatine phosphokinase (CPK) and edema. Laboratory AEs were asymptomatic and occurred early after treatment initiation, with a median time to onset of 15 days for CPK and 17 days for aminotransferase elevations. These events generally resolved within weeks, with median resolution times of 63  days and 43  days, respectively.

Clinical AECIs developed more gradually. Median time to onset for edema was 37 days, with longer durations observed for rash, periorbital edema, and hypertension. Most AECIs were mild to moderate in severity, and dose reductions or treatment discontinuation due to AEs occurred in a minority of patients.

AEs were monitored for 30  days following the final pimicotinib dose, supporting characterization of both on-treatment and short-term post-treatment safety and informing ongoing management during prolonged exposure. The authors concluded that “longer-term pimicotinib [treatment] continued to provide sustained, robust antitumor activity with few AE-related discontinuations.”

Jean-Yves Blay (Centre Léon Bérard, Lyon, France) presented complementary safety data from a pooled safety analysis of vimseltinib in patients with TGCT who had not received prior CSF-1R inhibitor therapy. The analysis included 164 patients treated across cohort  A of a phase 1/2 study and the phase 3 MOTION trial.

Median treatment duration was 20.7  months, with nearly two-thirds of patients receiving therapy for at least 18 months. Most treatment-emergent AEs (TEAEs) were grade 1 or 2, occurred within the first year of treatment, and did not worsen over time. Serious TEAEs were infrequent, and investigators reported no new or late‑onset safety signals with prolonged exposure.

Common treatment-related events, including edema and rash, were managed using standard institutional protocols. The analysis found no evidence of cholestatic hepatotoxicity or drug-induced liver injury, with aminotransferase elevations generally resolving within weeks.

The authors concluded that these findings provide important updates in long-term safety monitoring and treatment planning in TGCT, particularly for patients with symptomatic disease who are not candidates for surgery. This highlights the need for individualized management over extended treatment durations.

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