ID #282 Tovorafenib-related Hair Color Changes A Study Of Hair Micro-structure And Relation To Tumor Response In Low Grade Gliomas

Background

Tovorafenib, an oral pan-RAF kinase inhibitor, is used in BRAF altered pediatric low-grade gliomas (pLGGs) [1][2]. Targeted therapies such as tovorafenib induce hair color change [3] [4].

Objective

Describe hair color change pattern in patients treated with Tovorafenib, hair micro-structure and clinical course of patients.

Methods

Pediatric patients with BRAF-altered pLGGs were treated with tovorafenib (420 mg/m²) for up to 6 months. MRI monitored tumor progression. Photographs, optical and electron microscopy captured hair discoloration .

Results

Between 2022 and 2025, five children were included, mostly after multiple prior therapies. Related manageable toxicities were CPK elevation, dermatologic effects, and reversible growth-related issues. All patients experienced hair color changes, ranging from partial to complete discoloration, which correlated with a decrease in melanin granule density on electron microscopy without significant change in granule size. Tumor reduction and stability were observed in 4 of 5 patients. More pronounced hair discoloration seemed to be associated with better tumor response, while the weakest discoloration was observed in the single patient who later progressed and died from hydrocephalus-related complications.

Conclusion

Tovorafenib-induced hair color change is frequent and a decrease in melanin granule density is observed in patients treated with tovorafenib.

1. Kilburn LB, Khuong-Quang D-A, Hansford JR, Landi D, van der Lugt J, Leary SES, Driever PH, Bailey S, Perreault S, McCowage G, Waanders AJ, Ziegler DS, Witt O, Baxter PA, Kang HJ, Hassall TE, Han JW, Hargrave D, Franson AT, Yalon Oren M, Toledano H, Larouche V, Kline C, Abdelbaki MS, Jabado N, Gottardo NG, Gerber NU, Whipple NS, Segal D, Chi SN, Oren L, Tan EEK, Mueller S, Cornelio I, McLeod L, Zhao X, Walter A, Da Costa D, Manley P, Blackman SC, Packer RJ, Nysom K. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med , 2024 30: 207–217.

2. Nysom K, Kilburn LB, Leary SES, Landi DB, de Vos-Kerkhof E, Perreault S, Witt O, Ziegler DS, Hernáiz Driever P, Franson AT, Baxter PA, Whipple NS, Kline C, Segal D, Jabado N, Bailey S, McCowage G, Hansford JR, Khuong-Quang D-A, Gottardo NG, Hassall T, Han JW, Yalon Oren M, Chi SN, Qiu J, Da Costa D, Govinda Raju S, Manley P, Hargrave D. Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial. Neuro Oncol , 2025 27: 1341–1355.

3. Du R, Wang X, Ma L, Larcher LM, Tang H, Zhou H, Chen C, Wang T. Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China. BMC Cancer , 2021 21: 206.

4. André N, Donzé C, Revon-Rivière G. Striped Hair Colour Change on Tovorafenib in an 18-Year-Old Boy With a Brainstem Low-Grade Glioma. Pediatr Blood Cancer , 2025 72: e31567.

5. Tomes, C., Jones, J. T., Carr, C. M., & Jones, D. Three-dimensional imaging and analysis of the surface of hair fibres using scanning electron microscopy. International Journal of Cosmetic Science, 29(6), 475–483, 2007