Real world data on young patients with high-risk diffuse large B-cell lymphoma treated with R-CHOP or R-CHOEP - MYC, BCL2 and BCL6 as prognostic biomarkers

TY - JOUR

T1 - Real world data on young patients with high-risk diffuse large B-cell lymphoma treated with R-CHOP or R-CHOEP - MYC, BCL2 and BCL6 as prognostic biomarkers

AU - Pedersen, Mette Ølgod

AU - Gang, Anne Ortved

AU - Brown, Peter

AU - Pedersen, Michael

AU - Knudsen, Helle

AU - Nielsen, Signe Ledou

AU - Poulsen, Tim

AU - Wirenfeldt Klausen, Tobias

AU - Høgdall, Estrid

AU - Nørgaard, Peter

PY - 2017/10

Y1 - 2017/10

N2 - Background: Double expression of MYC and BCL2 proteins (DE) and double-hit MYC+BCL2/BCL6 translocations (DH) were established as important biomarkers in patients with diffuse large B-cell lymphoma (DLBCL) by the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Whether this applies to the subgroup of young patients with high risk DLBCL is not known. We previously found that in a uniform retrospective population-based cohort of patients aged 18–60 years with high-risk DLBCL, the addition of etoposide to R-CHOP chemotherapy (R-CHOEP) resulted in improved survival mainly in patients with germinal center B-cell like (GCB) immunophenotype. The aim of this study was to investigate the prognostic and predictive value of DE and DH in this patient cohort. Methods: Data on all young Danish patients diagnosed with de novo high-risk DLBCL 2004–2008 and treated with R-CHOP or R-CHOEP were obtained from the Danish Lymphoma database (n = 159). Tumor samples were available from 103 patients. MYC and BCL2 proteins were analyzed with quantitative immunohistochemistry (IHC) using different cut off values. MYC-, BCL2- and BCL6-translocations were examined with fluorescent in situ hybridization (FISH). Results: DE with MYC>75% and BCL2>85% was an independent negative prognostic marker of progression free survival (PFS) in patients treated with R-CHOP but not R-CHOEP (p<0.001), also after exclusion of patients with DH. A predictive effect of DE for response (PFS) to R-CHOEP vs. R-CHOP was almost significant (p = 0.07). DH was not prognostic in this patient cohort. Conclusion: In young patients with high-risk DLBCL, treatment with R-CHOEP may overcome the negative prognostic impact of DE observed in patients treated with R-CHOP.

AB - Background: Double expression of MYC and BCL2 proteins (DE) and double-hit MYC+BCL2/BCL6 translocations (DH) were established as important biomarkers in patients with diffuse large B-cell lymphoma (DLBCL) by the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Whether this applies to the subgroup of young patients with high risk DLBCL is not known. We previously found that in a uniform retrospective population-based cohort of patients aged 18–60 years with high-risk DLBCL, the addition of etoposide to R-CHOP chemotherapy (R-CHOEP) resulted in improved survival mainly in patients with germinal center B-cell like (GCB) immunophenotype. The aim of this study was to investigate the prognostic and predictive value of DE and DH in this patient cohort. Methods: Data on all young Danish patients diagnosed with de novo high-risk DLBCL 2004–2008 and treated with R-CHOP or R-CHOEP were obtained from the Danish Lymphoma database (n = 159). Tumor samples were available from 103 patients. MYC and BCL2 proteins were analyzed with quantitative immunohistochemistry (IHC) using different cut off values. MYC-, BCL2- and BCL6-translocations were examined with fluorescent in situ hybridization (FISH). Results: DE with MYC>75% and BCL2>85% was an independent negative prognostic marker of progression free survival (PFS) in patients treated with R-CHOP but not R-CHOEP (p<0.001), also after exclusion of patients with DH. A predictive effect of DE for response (PFS) to R-CHOEP vs. R-CHOP was almost significant (p = 0.07). DH was not prognostic in this patient cohort. Conclusion: In young patients with high-risk DLBCL, treatment with R-CHOEP may overcome the negative prognostic impact of DE observed in patients treated with R-CHOP.

KW - Adolescent

KW - Adult

KW - Antibodies, Monoclonal, Murine-Derived/administration & dosage

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Biomarkers, Tumor/genetics

KW - Cyclophosphamide/administration & dosage

KW - Doxorubicin/administration & dosage

KW - Etoposide/administration & dosage

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization, Fluorescence

KW - Kaplan-Meier Estimate

KW - Lymphoma, Large B-Cell, Diffuse/diagnosis

KW - Male

KW - Middle Aged

KW - Prednisone/administration & dosage

KW - Prognosis

KW - Proto-Oncogene Proteins c-bcl-2/genetics

KW - Proto-Oncogene Proteins c-bcl-6/genetics

KW - Proto-Oncogene Proteins c-myc/genetics

KW - Retrospective Studies

KW - Risk Factors

KW - Vincristine/administration & dosage

KW - Young Adult

U2 - 10.1371/journal.pone.0186983

DO - 10.1371/journal.pone.0186983

M3 - Journal article

C2 - 29088292

SN - 1932-6203

VL - 12

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 10

M1 - e0186983

ER -