The Incidence and Treatment Response of Double Expression of MYC and BCL2 in Patients with Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

Abstract

MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to establish the incidence of double expressor status in patients with de novo DLBCL and identify the predictive value of this biomarker on treatment response through systematic review and meta-analysis. PubMed and Embase were searched for studies published through December 2019 that reported proportions of double expressor DLBCL. The pooled proportions of MYC and BCL2 expression, both alone and in combination, were computed using the inverse variance method for calculating weights and by the DerSimonian–Laird method. The pooled odds ratios (ORs) of complete remission (CR) rate were calculated, and meta-regression analysis was conducted to explore heterogeneity. Forty-one studies (7054 patients) were included. The pooled incidence of double expressor status in DLBCL was 23% (95% confidence interval [CI], 20–26%), with an adjusted estimate of 31% (95% CI, 27–36%). Neither MYC/BCL2 protein cutoff values, race, mean, or median age of included patients, or overall study quality was a significant factor of heterogeneity (p ≥ 0.20). Cases without double expressor status demonstrated a higher probability of CR to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment (OR, 2.69; 95% CI, 1.55–4.67). Our results reaffirm the predictive power of this important biomarker.

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

“…An MYC expression was detected in 23.4% of HIV‐associated DLBCL, and 13% were DE, most of them of the non‐GC phenotype. This incidence is slightly lower than that reported in DLBCL series of immunocompetent patients (20–30%) 14,55–57 . Of note, MYC positivity tended to be associated with worse PFS, and DE was significantly associated with shorter probability of OS and PFS.…”

“…This incidence is slightly lower than that reported in DLBCL series of immunocompetent patients (20–30%). 14 , 55 , 56 , 57 Of note, MYC positivity tended to be associated with worse PFS, and DE was significantly associated with shorter probability of OS and PFS. These results support the consideration, made in general DLBCL, that MYC and BCL2 coexpression, but not MYC expression alone, is associated with a worse prognosis.…”

The significance of upfront autologous stem cell transplantation for high‐intermediate/high‐risk stage IV diffuse large B‐cell lymphoma

“…The association of DEL and inferior survival ( p = .001) was the anticipated result because many trials have shown it before 35–37 . The need and the benefit of treatment intensification in DEL/DHL patients was demonstrated in retrospective trials.…”

“…The association of DEL and inferior survival ( p = .001) was the anticipated result because many trials have shown it before. 35 , 36 , 37 The need and the benefit of treatment intensification in DEL/DHL patients was demonstrated in retrospective trials. In trial by Lansburg et al, 38 patients with intensive (DA‐EPOCH‐R, R‐HyperCVAD, R‐CODOX‐M/IVAC) ICT experienced superior rates in 3‐year RFS, compared with R‐CHOP (75% vs. 51% respectively, p = .003).…”

“Double expressor” diffuse large B-cell lymphoma: A case report and literature review

“…In the following years, the number of researches that do not favor therapy intensification for patients with DEL [29][30][31] notably outnumbered those who do favor intensification [32]. Systematic review and meta-analysis by Hwang et al [33], that included 7054 patients from 41 studies, confirmed that CR rate is significantly lower in newly diagnosed DEL than non-DEL DLBCL patients. However, one of the main limitations of the study was its inability to compare different treatment approaches and CR rates due to insufficient data.…”