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Master Thesis

Impact pronostique de la cellule d’origine (COO), de l’expression des protéines BCL2 et MYC et de la mutation MYD88 L265P au diagnostic de Lymphome B Diffus à Grandes Cellules : résultats de l’essai randomisé multicentrique GOELAMS-075

Abstract : The prognostic value of COO classification by immunohistochemistry (IHC) for de novo untreated advanced DLBCL remains controversial after Rituximab-based frontline therapy. Other biomarkers such as BCL2 or MYC protein expression have been proposed to predict survival. MYD88 L265P mutational status had never been explored in a randomized trial. IHC characteristics and MYD88 L265P status were investigated. Three hundred twenty-three patients (pts) younger than 60 years with de novo untreated advanced DLBCL were randomized in the french prospective multicenter trial GOELAMS-075 to receive either 8 courses of RCHOP14 (n=161) or 2 courses of RCEEP and 1 course of Rituximab-Methotrexate-Cytarabine (RMC) followed by intensive BEAM conditionning with autologous transplant (ASCT) (n=162) upon negative interim PET-CT (visual analysis). In case of positivity, salvage regimen followed by ASCT was applied. COO determination using Hans algorithm, BCL2 protein expression (50% and 70%) and MYC protein expression (40%) were recorded. COO analysis could be performed for 88% of pts : 31% GC, 42% NGC and 27% PMBL, without treatment imbalance. There was no PFS or OS difference between GC and NGC subtypes (PFS: 67%±5% GC and 73%±4% NGC; OS: 75%±5% GC and 78%±4% NGC), whereas PMBL prognosis was significantly better (PFS: 88%±4%, HR=0,3; CI95% [0,14-0,71] p=0,01; OS: 96%±2% HR=0,15; CI95%[0,04-0,51] p=0,002). No further advantage of treatment was observed in all 3 COO subtypes. BCL2 and MYC protein expression (28% of coexpression cases), determined for 91% and 63% of cases respectively, did not impair prognosis, regardless of treatment arm. Positive MYD88 L265P mutation was observed in 7,8% cases (n=11/141), and was associated with advanced age, extranodal site, BCL2 and MYC protein overexpression, without any prognostic impact. In younger patients, outcome of IHC defined GC and NGC subtype of non-PMBL DLBCL was not different following R-CHOP14 or intensive treatment including ASCT. Conversely,the good prognosis of PMBL subtype with excellent PFS and OS was confirmed. Regardless of treatment arm, BCL2 or MYC or both overexpression did not impair significantly the prognosis. No prognostic value of MYD88 L265P status was found. IHC defined COO or BCL2/MYC overexpression could not identify DLBCL in need of intensive therapy with ASCT.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-01246394
Contributor : Bu Carreire Université de Bordeaux <>
Submitted on : Friday, December 18, 2015 - 2:36:57 PM
Last modification on : Wednesday, August 23, 2017 - 4:32:38 PM
Long-term archiving on: : Saturday, March 19, 2016 - 1:30:15 PM

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Gaëlle Laboure. Impact pronostique de la cellule d’origine (COO), de l’expression des protéines BCL2 et MYC et de la mutation MYD88 L265P au diagnostic de Lymphome B Diffus à Grandes Cellules : résultats de l’essai randomisé multicentrique GOELAMS-075. Médecine humaine et pathologie. 2015. ⟨dumas-01246394⟩

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