Double or triple-expressor lymphomas: prognostic impact of immunohistochemistry in patients with diffuse large B-cell lymphoma

Peña, Camila; Bolaños-Villegas, Pablo; Cabrera, María Elena

doi:10.1016/j.htct.2019.04.002

Cited by 7 publications

(6 citation statements)

References 10 publications

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“…Concurrent double expressor status has even been associated with poorer outcomes in tumors harboring DH cytogenetics [17,20]. Further, cases with double expressor status have demonstrated distinctive clinical features such as older age and advanced stage [20,21], higher LDH level [22], higher Ki67 proliferation index [23], and higher international prognostic index [24]. The revised 2016 WHO classification recommends cutoff values of 40% for MYC and 50% for BCL2 expression as assessed by immunohistochemistry (IHC) [7]; however, actual cutoff values have varied widely among published studies.…”

Section: Introductionmentioning

confidence: 99%

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

Hwang

Suh

Kim

et al. 2021

Cancers

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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.

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Section: Introductionmentioning

confidence: 99%

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

Hwang

Suh

Kim

et al. 2021

Cancers

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“…20 Although DE lymphomas are not a distinct clinicopathological entity in the revised World Health Organization classification 2 , patients with DLBCL featuring high MYC/BCL2 co-expression by IHC have been reported to be more likely to have advanced disease stage, high Ki67 proliferative index scores, poor ECOG PS scores, multiple extranodal disease sites, and high-risk R-IPI scores. 22,40,41 In this analysis, we did not observe any major differences in the clinicopathological characteristics of patients with vs without high BCL2/MYC co-expression by RNA-seq, except for a slightly higher proportion of patients in the high BCL2/MYC group having elevated lactate dehydrogenase levels. This result may be a reflection of the non-GCB enriched population within this study, with more ABC subtype than included in previous studies (71% in this analysis vs 38%-48% in previous studies 22,40 ).…”

Section: Discussionmentioning

confidence: 53%

Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL coexpressing BCL2 and MYC in the phase 3 PHOENIX trial

et al. 2023

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Diffuse large B-cell lymphoma (DLBCL) with high co-expression of BCL2 and MYC proteins (double-expressor [DE] lymphoma), is considered an adverse prognostic indicator associated mostly with non-germinal center B-cell-like (non-GCB) DLBCL. BCL2/MYC overexpression is associated with B-cell receptor (BCR) pathway activation and, consequently, DE DLBCL may be sensitive to BCR inhibitors. We assessed whether high BCL2/MYC co-expression by RNA sequencing could identify a patient subset responsive to ibrutinib using baseline biopsies from the PHOENIX trial (NCT01855750), which evaluated the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-GCB DLBCL. BCL2/MYC RNA expression was correlated with lower event-free survival (EFS) and overall survival (OS) using Kaplan-Meier estimates with Cox regression and log-rank testing. In total, 234/766 (30.5%) patients had high BCL2/MYC co-expression: 123/386 (31.9%) received ibrutinib plus R-CHOP and 111/380 (29.2%) received R-CHOP. EFS was superior with ibrutinib plus R-CHOP vs R-CHOP alone in patients with high BCL2/MYC co-expression (HR, 0.646; 95% CI, 0.424-0.984; P=.0403), but there was no significant impact on OS (P=.1574). However, EFS (HR, 0.381; 95% CI, 0.193-0.752; P=.0039) and OS (HR, 0.234; 95% CI, 0.078-0.707; P=.0050) showed clinically meaningful improvement with ibrutinib plus R-CHOP over R-CHOP alone in patients aged <60 years with high BCL2/MYC co-expression. We observed a significant association between high BCL2/MYC co-expression and activated B-cell-like (P<.0001) and MYD88L265P/CD79B-mutated (P=.0016) subtypes of DLBCL. Consequently, high BCL2/MYC co-expression identifies a subset of non-GCB DLBCL that may be preferentially responsive to ibrutinib and warrants further investigation. ClinicalTrials.gov NCT01855750.

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“…Patients with HGBL typically exhibit advanced disease, extranodal disease, involvement of the bone marrow, an elevated lactate dehydrogenase level, and a high international prognostic score [ 9 ]. According to the recent WHO classification of lymphoid neoplasms (2016), HGBLs with c-Myc, Bcl2, and/or Bcl6 rearrangement were classified as double expressors and/or triple expressors, respectively [ 10 ]. Cyclin D1 expression is characteristic of MCL [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of c-Myc, Bcl2, Bcl6, and Cyclin D1 in High-Grade B-Cell Lymphoma

Ali¹,

Rathore²,

Jahangir³

et al. 2022

Cureus

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Double or triple-expressor lymphomas: prognostic impact of immunohistochemistry in patients with diffuse large B-cell lymphoma

Cited by 7 publications

References 10 publications

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

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

Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL coexpressing BCL2 and MYC in the phase 3 PHOENIX trial

Expression of c-Myc, Bcl2, Bcl6, and Cyclin D1 in High-Grade B-Cell Lymphoma

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