PROGNOSTIC IMPACT OF BCL2 AND MYC EXPRESSION AND TRANSLOCATION IN UNTREATED DLBCL: RESULTS FROM THE PHASE III GOYA STUDY

Abstract

Introduction: DLBCL pts with tumours co‐expressing BCL2 and MYC (dual‐expressor, DE) or with dual gene translocations (double‐hit, DH) have poor outcomes but prognostic relationships between cell‐of‐origin (COO) subtype (ABC vs GCB) and BCL2/MYC are unclear. We report predefined exploratory analyses of the prognostic effects of BCL2 positivity (+), MYC+, DE and DH, in relation to COO, in the Phase III GOYA study (NCT01287741). Methods: Pts with previously untreated DLBCL were randomised 1:1 to receive obinutuzumab or rituximab plus 6 or 8 cycles of CHOP. Using a Ventana investigational‐use IHC assay (BCL2 antibody clone, 124; c‐MYC, Y69), pretreatment tumour samples were analysed at a central laboratory. Samples stained within the limit of BCL2 ( =50% of tumour cells; MYC IHC+, >=40% of tumour cells. Vysis LSI Dual Color Break Apart FISH Probes identified BCL2 and MYC translocations: FISH+, >=50%. COO classification of RNA extracts used a NanoString Lymphoma Subtyping gene expression assay. Univariate Cox regression analysis of investigator‐assessed PFS was performed. Covariates for multivariate analysis were treatment arm (Tx), IPI score, no. of CHOP cycles and COO. (Figure Presented) Results: Baseline characteristics, including IPI score, were similar for biomarker evaluable and ITT populations. Prevalence of BCL2 IHC+, MYC IHC+, DE and DH was 49%, 83%, 42% and 3.6%, respectively. Prevalence by COO: BCL2 IHC+, 75% in ABC and 38% in GCB; MYC IHC+, 95% in ABC and 76% in GCB; DE, 72% in ABC and 29% in GCB; DH, 7% in GCB and 0% in ABC (19/20 DH pts were GCB; 1 unclassified). In univariate analysis, BCL2 IHC+, DE and DH were associated with poorer prognosis (Table). Multivariate analysis confirm the poor prognosis of BCL2 IHC+ pts, independent of Tx, IPI score, no. of CHOP cycles and COO. Context‐dependent effects of MYC IHC+ suggest an association with poorer prognosis in BCL2 IHC‐ pts while BCL2 IHC+ pts drive a suggested prognostic effect in DE pts (Figure). Poor prognosis of DH pts was independent of Tx, IPI score and no. of CHOP cycles, but no. of pts was low. Conclusions: Robust identification and analysis of biomarker subgroups confirm the prognostic importance of DH and BCL2 IHC+, and demonstrate that the prognostic effect of BCL2 IHC+ is independent of COO in DLBCL pts in the GOYA study.