EZH2 Overexpression in Multiple Myeloma: Prognostic Value, Correlation With Clinical Characteristics, and Possible Mechanisms

Abstract

Background: EZH2 is a histone methyltransferase that suppresses genes involved in cell cycle control. Overexpression of EZH2 has been associated with a poor prognosis in various malignancies. Pawlyn et al recently reported poor outcomes in patients with multiple myeloma and overexpression of EZH2. In order to validate these findings, we analyzed EZH2 expression and outcomes among patients from the CoMMpass study. Patients and Methods: We extracted clinical, expression, and genomic data from Interim Analysis 13 of the MMRF CoMMpass study, which harbors data from over 1000 patients with multiple myeloma. Correlations were drawn between EZH2 expression and common genetic mutations. We analyzed the association of EZH2 overexpression with progression-free (PFS) and overall survival (OS). Results: The estimated median PFS for patients with EZH2 overexpression was 20.2 months (95% confidence interval [CI], 16.3-25.5 months) compared with 37.2 months (95% CI, 31.5-40.7 months) for patients without (P