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

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.

Fig. 1. Case report timeline.

Timeline summarizing the patient’s clinical history, highlighting key genomic findings and treatment interventions. IMRT intensity modulated radiation therapy, NGS next generation sequencing.

Fig. 2. Axial T1 MRI images of the brain through the course of treatment.

A First relapse; a 1.4 cm tumor was identified in the left external auditory canal three months after initial debulking surgery and prior to any systemic treatment. B Second relapse; after one year of adjuvant nivolumab, the patient experienced a second relapse when a new 4.0 cm mass was identified along the floor of the left middle cranial fossa with mass effect on the left temporal lobe. C Post-operative imaging; the patient underwent intracranial tumor resection after two cycles of neoadjuvant ipilimumab/ nivolumab. D Representative surveillance imaging while on tazemetostat; eighteen months post-operatively and fifteen months into tazemetostat therapy, the patient continued to demonstrate no evidence of relapsed disease. Blue arrows indicate the location of the tumor or resection site.