Poorer DLBCL Survival Outcomes Linked to Dual Expression of MYC, BCL2

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Dual expression of MYC and BCL2 was associated with worse survival among patients with GCB-like DLBCL, though this status was not associated with any outcomes among patients with ABC-like DLBCL.
Dual expression of MYC and BCL2 was associated with worse survival among patients with GCB-like DLBCL, though this status was not associated with any outcomes among patients with ABC-like DLBCL.

Cell-of-origin (COO) classification in 2 prospective, randomized trials of diffuse large B cell lymphoma (DLBCL) did not identify prognostic subgroups, though dual expression of MYC and BCL2 did predict poor survival in germinal center B cell (GCB)-like DLBCL.1

This study examined 452 formalin-fixed paraffin-embedded samples from RICOVER-60 (ClinicalTrials.gov Identifier: NCT01478542) and R-MegaCHOEP, which are both part of the German High-Grade Non-Hodgkin Lymphoma Study Group.

RICOVER-60 enrolled patients older than 60 years across all International Prognostic Index (IPI) groups, and R-MegaCHOEP enrolled patients 60 years or younger with age-adjusted IPI of 2 or 3.

Researchers used the Lymph2Cx assay, a parsimonious digital gene expression (NanoString)-based test, for COO classification, immunohistochemistry to determine MYC and BCL2 expression, and fluorescent in situ hybridization to assess MYC, BCL2, and BCL6 rearrangements.

Classification of COO was successful in 92% (414) of samples. Though COO correctly differentiated activated B cell (ABC)-like DLBCL from GCB-like DLBCL, these classifications were not associated with event-free survival, progression-free survival, or overall survival in either trial, even when analyses adjusted for IPI.

“We were not surprised by the absence of associations with COO classification and survival or outcomes as there were some indications that the COO might not be prognostic in at least all clinical trial cohorts,” said senior author German Ott, MD, a collaborator on the German High Grade Lymphoma Study group and professor in the department of clinical pathology, IKP Stuttgart, Germany, in an interview with Cancer Therapy Advisor.

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He emphasized that these results might not be applicable to other trials: “although the COO might not be prognostic in all trials, it identifies tumor subgroups with distinct genetic alterations and biology, hence it is predictive and may mandate different treatment strategies.”

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