In situ BCL2 expression is an independent prognostic factor in HIV‐associated DLBCL, a LYMPHOVIR cohort study

Abstract

The prognostic value of cell of origin (COO) classification and BCL2 expression is not well established in diffuse large B-cell lymphoma (DLBCL) patients with human immunodeficiency virus (HIV) infection in the recent era. Phenotypic patterns were determined by immunohistochemistry (IHC) of pathological samples from patients with HIV-associated DLBCL prospectively enrolled in the French AIDS and Viral Hepatitis CO16 Lymphovir cohort between 2008 and 2015. Molecular subgroup classification into germinal centre B-cell (GCB) and non-GCB subtypes was determined using the Hans algorithm. Among 52 samples of systemic DLBCL subjected to centralized pathological analysis, 25 of the 42 tested for BCL2 expression were positive. Samples were further classified into GCB (n = 19) and non-GCB (n = 16) subtypes and 17 remained unclassified. In multivariable analysis, BCL2 expression was an independent pejorative prognostic biomarker [4-year progression-free survival (PFS): 52% for BCL2 + vs. 88% for BCL2 À , P = 0Á02] and tended to reduce 4-year overall survival (OS) (63% for BCL2 + vs. 88% for BCL2 À , P = 0Á06). The difference between CGB and non-GCB subtypes on PFS and OS did not reach significance (4-year PFS: 79% for GCB vs. 53% for non-GCB, P = 0Á24 and 4-year OS: 78% for GCB vs. 69% for non-GCB, P = 0Á34). BCL2 expression determined by IHC is an independent pejorative prognostic biomarker in HIV-associated DLBCL in the recent era. This supports the investigation of new therapeutic strategies in patients with BCL2 expression.

Genetic and phenotypic characterisation of HIV‐associated aggressive B‐cell non‐Hodgkin lymphomas, which do not occur specifically in this population: diagnostic and prognostic implications

“…Herein, in line with a previous report by Chao et al ., we identified a higher frequency of non‐GC types in HIV‐associated DLBCL than that reported in immunocompetent patients 41 . Regarding the prognostic impact of COO, two previous studies on HIV‐associated DLBCL showed that the Hans algorithm could identify cases with worse outcomes 43,47 . In the present study, a larger series of HIV‐associated DLBCL treated with RCHOP we observed that non‐GC cases tended to have a worse OS and PFS than GC cases, although without statistical significance.…”

Viral Agents as Potential Drivers of Diffuse Large B-Cell Lymphoma Tumorigenesis

“…Previous clinical investigations of the LYMPHOVIR cohort revealed that the PFS in PLHIV with DLBCL was not different from that of their HIV-negative counterparts, and that only lymphoma-specific clinical variables predicted survival in this scenario [ 46 ]. According to the findings of [ 146 ], tumor histogenesis is an independent predictor of lymphoma-specific survival in PLHIV with DLBCL in the cART era. These findings may encourage the use of BCL2-targeted drugs in future prospective investigations of HIV-infected DLBCL patients [ 146 ].…”

“…According to the findings of [ 146 ], tumor histogenesis is an independent predictor of lymphoma-specific survival in PLHIV with DLBCL in the cART era. These findings may encourage the use of BCL2-targeted drugs in future prospective investigations of HIV-infected DLBCL patients [ 146 ].…”

Clinical and Molecular Properties of Human Immunodeficiency Virus-Related Diffuse Large B-Cell Lymphoma

“…Some studies showed that the frequency of double expressors is similar between HIV-DLBCL and immunocompetent patients ( 193 ). However, its prognostic relevance was not yet addressed in the HIV-infected context, even though cMYC ( 179 ) and BCL2 ( 194 ) expression were described separately as prognostic factors for HIV-DLBCL. Similarly, another immunohistochemistry study detected high frequency (around 40%) of HIV-DLBCL samples positive for BCL6 and MUM1 ( 180 ).…”