MYD88 L265P Mutations, But No Other Variants, Identify a Subpopulation of DLBCL Patients of Activated B-cell Origin, Extranodal Involvement, and Poor Outcome

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Jordina RoviraArmando López-Guillermo

Abstract

Mutations in MYD88 are found in different lymphoproliferative disorders associated with particular biologic characteristics and clinical impact. The aim of this study was to analyze the incidence of MYD88 mutations and its clinical impact in diffuse large B-cell lymphoma (DLBCL). The incidence, clinicobiological features, and outcome of 213 patients (115 M/98 F; median age, 65 years) with DLBCL treated with immunochemotherapy in a single institution according to MYD88 mutational status as assessed by an allele-specific PCR assay were analyzed. The cell of origin (COO) was determined in 129 cases by gene expression. MYD88 mutations were found in 47 cases (22%), including L265P in 39 and S219C and M232F in 4 cases, respectively. Patients with MYD88 L265P were older, presenting frequent extranodal involvement, and mostly corresponded to activated B-cell like (ABC) subtype, whereas no preference in COO was observed in patients with other MYD88 mutations. Five-year overall survival (OS) for MYD88 wild-type, MYD88 L265P, and other variants was 62%, 52%, and 75%, respectively (P = 0.05). International Prognostic Index (IPI) (HR, 2.71; P < 0.001) and MYD88 L265P (HR, 1.786; P = 0.023) were independent variables predicting OS in the mul...Continue Reading

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