Impact of treatment variability and clinicopathological characteristics on survival in patients with Epstein‐Barr‐Virus positive diffuse large B cell lymphoma

Abstract

Patients with EBV-positive diffuse large B cell lymphoma not otherwise specified (EBV + DLBCL (NOS)) recurrently present with advanced age and reduced performance status. They are therefore insufficiently represented in clinical trials and treatment is likely to differ. Here we assess clinicopathological characteristics, therapeutic variability and clinical outcome in the largest consecutively diagnosed EBV + DLBCL (NOS) cohort published to date (n = 80; median age 70 years; range 19-90). Centralized and systematic haematopathological panel review was performed. By immunohistochemistry 60/80 patients were CD30-positive. Further, we identified nine EBV + DLBCL (NOS) patients with associated or composite peripheral T cell lymphoma at diagnosis or relapse (preceded by clonal T cell populations within the initial DLBCL biopsy in 4/5 cases). Most patients (80%) were treated with R-CHOP-type therapy and 16 patients received none or less intensiveprotocols. Upon univariate analysis both R-CHOP-type therapy (OS: P < 0.0001; PFS: P = 0.0617) and negativity for CD30 (OS: P = 0.0002; PFS: P = 0.0002) showed a protective 66 effect, maintained upon multivariate analysis. In a propensity-score matched analysis with a cohort of non-EBV + DLBCL (NOS) patients, balanced for all revisedinternational prognostic index factors, we found an EBV-association to hold no significant impact on progression-free and overall survival whilst exhibiting a trend favouring EBV-negativity (OS: P = 0.116; PFS: P = 0.269). Our findings provide insight into the clinical course of EBV + DLBCL (NOS), highlight the ramifications of CD30-expression and underline the superior therapeutic efficacy of R-CHOP immunochemotherapy. Alternative therapies, incorporating tumour biology (e.g. CD30 directed therapies) need to be explored in EBV + DLBCL (NOS) patients. Moreover our data advert to the close relationship between EBV + DLBCL (NOS) and peripheral T cell lymphomas.

EBV‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2020 update on diagnosis, risk‐stratification and management

“…And, CD30 expression is increased in patients with EBV+ DLBCL (43% vs 16% in EBV‐negative DLBCL) and has been associated with worse OS . Similar results were found in a German study, in which EBV+ DLBCL patients had a high incidence of CD30 expression (75%), and lack of expression of CD30 was associated with an improved survival . Survivin affects cellular apoptosis through indirect mechanisms that lead to inhibition of caspase 9 .…”

Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing

“…Clinical data 1. Most samples of the current study were previously investigated for the impact of treatment variability and clinicopathological baseline characteristics on clinical outcome in EBV + DLBCL (NOS) 10 .…”

“…Although recent observations relativized EBV as an independent risk factor, several studies found EBV + DLBCL (NOS) patients to be significantly enriched for adverse confounding clinical factors, such as stage, impaired performance status, advanced age, and significant canonical and alternative nuclear factor κB (NFκB)-pathway activation 10 . Altogether this resulted in a high number of cases with non-germinal center B-cell-like immunophenotype 2,7,[11][12][13][14] .…”

Clinicopathological characteristics and MYC status determine treatment outcome in plasmablastic lymphoma: a multi-center study of 76 consecutive patients

“…Previous clinicopathological studies emphasized the role of MYCrearrangement status while a systematical assessment of clinical implications regarding MYC amplification has so far not been undertaken 7 . The antigen CD30, while pathogonomonic in anaplastic large cell lymphoma, is universally expressed is several types of lymphoma, including classical Hodgkin lymphoma (cHL), but more recent studies identified it as a potential therapeutic target in B-cell non-Hodgkin lymphoma subtypes as well 8 . Brentuximab vedotin as a potential targeted therapeutic approach is a monoclonal CD30 antibody-drug conjugate (monomethyl auritatine E), which is already approved, due to encouraging results for several indications, including relapsed and refractory (cHL) and CD30positive peripheral T-cell lymphoma 9,10 .…”