MyD88 Mutation in Elderly Predicts Poor Prognosis in Primary Central Nervous System Lymphoma: Multi-Institutional Analysis.

Abstract

Recent genetic analysis of primary central nervous system lymphoma (PCNSL) showed that the MyD88 L265P mutation, which is related to NF-κB signaling, was a genetic hallmark for PCNSL; thus it could serve as a genetic marker for diagnosis and a potential target for molecular therapy. However, the role of the MyD88 mutation in PCNSL has not been defined. In this study, we investigated the role of the MyD88 mutation and clinical features of PCNSL-treated patients at several institutions to determine its significance as a prognostic factor. Forty-one PCNSL (diffuse large B-cell type) patients from 8 institutions were included in this study. Their median age was 68 years; median follow-up was 26.7 months; median overall survival was 26.7 months; and their 1-year, 3-year, and 5-year survival rates were 75.6%, 58.5%, and 43.9%, respectively. Deoxyribonucleic acid was extracted from frozen tissue, and the MyD88 L265P mutation was evaluated by polymerase chain reaction and direct sequencing. The MyD88 L265P mutation was found in 61.0% (25/41) of cases. Kaplan-Meier analysis revealed that neither MyD88 L265P mutation nor age >65 years alone significantly predicted overall survival relative to MyD88 wild type and age <65. The MyD88 L265P mutation was predominantly present in patients aged >65 years. Among age >65 patients, the MyD88 L265P mutation portended a worse overall survival compared with the MyD88 wild type (11.5 vs. 56.2 months P < 0.04). The MyD88 L265P mutation predicted a poor prognosis in elderly PCNSL patients. A new tailor-made treatment strategy might be needed for these patients.