Relapse-free survival in a pediatric patient with recurrent EZH2-mutant melanoma treated with adjuvant tazemetostat

Erin E Resch; Stavriani C Makri; Paola Ghanem; Ezra G Baraban; Kenneth J Cohen; Alan R Cohen; Evan J Lipson; Christine A Pratilas

doi:10.1038/s41698-025-00826-8

Relapse-free survival in a pediatric patient with recurrent EZH2-mutant melanoma treated with adjuvant tazemetostat

NPJ Precis Oncol. 2025 Feb 21;9(1):48. doi: 10.1038/s41698-025-00826-8.

Authors

Erin E Resch¹, Stavriani C Makri¹, Paola Ghanem², Ezra G Baraban³, Kenneth J Cohen¹, Alan R Cohen⁴, Evan J Lipson⁵, Christine A Pratilas⁶

Affiliations

¹ Division of Pediatric Oncology, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Division of Pediatric Neurosurgery, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Oncology, Bloomberg~Kimmel Institute for Cancer Immunotherapy and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Division of Pediatric Oncology, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cpratil1@jhmi.edu.

Abstract

Enhancer of zeste homolog 2 (EZH2) is an essential epigenetic regulator of H3K27 histone methylation and is mutated or overexpressed in a wide variety of cancers. In melanoma, EZH2 overexpression contributes to excessive trimethylation of H3K27 on tumor suppressor genes and has been proposed to be a mechanism of tumor progression and metastasis. EZH2-targeted therapies have been successfully used to treat patients with follicular lymphoma and epithelioid sarcoma, but their clinical use in melanoma has not been described. Here, we describe a pediatric patient with multiply relapsed melanoma harboring an EZH2 A692V missense mutation, treated adjuvantly with the EZH2 inhibitor tazemetostat, who experienced a prolonged relapse-free survival.