TY - JOUR
T1 - The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin
T2 - FIL-FOLL study
AU - Rossi, Davide
AU - Bruscaggin, Alessio
AU - La Cava, Piera
AU - Galimberti, Sara
AU - Ciabatti, Elena
AU - Luminari, Stefano
AU - Rigacci, Luigi
AU - Tucci, Alessandra
AU - Pulsoni, Alessandro
AU - Bertoldero, Giovanni
AU - Vallisa, Daniele
AU - Rusconi, Chiara
AU - Spina, Michele
AU - Arcaini, Luca
AU - Angrilli, Francesco
AU - Stelitano, Caterina
AU - Merli, Francesco
AU - Gaidano, Gianluca
AU - Federico, Massimo
AU - Palumbo, Giuseppe A.
PY - 2015
Y1 - 2015
N2 - Though most follicular lymphoma biomarkers rely on tumor features, the host genetic background may also be relevant for outcome. Here we aimed at verifying the contribution of candidate polymorphisms of FCreceptor, DNA repair and detoxification genes to prognostic stratification of follicular lymphoma treated with immunochemotherapy. The study was based on 428 patients enrolled in the FOLL05 prospective trial that compared three standard-of-care regimens (rituximab-cyclophosphamide-vincristine-prednisone versus rituximabcyclophosphamide-doxorubicin-vincristine-prednisone versus rituximab-fludarabine-mitoxantrone) for the first line therapy of advanced follicular lymphoma. Polymorphisms were genotyped on peripheral blood DNA samples. The primary endpoint was time to treatment failure. Polymorphisms of FCGR2A and FCGR3A, which have been suggested to influence the activity of rituximab as a single agent, did not affect time to treatment failure in the pooled analysis of the three FOLL05 treatment arms that combined rituximab with chemotherapy (P=0.742, P=0.252, respectively). These results were consistent even when the analysis was conducted by intention to treat, indicating that different chemotherapy regimens and loads did not interact differentially with the FCGR2A and FCGR3A genotypes. The genotype of MLH1, which regulates the genotoxic effect of doxorubicin, significantly affected time to treatment failure in patients in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone arm (P=0.001; q
AB - Though most follicular lymphoma biomarkers rely on tumor features, the host genetic background may also be relevant for outcome. Here we aimed at verifying the contribution of candidate polymorphisms of FCreceptor, DNA repair and detoxification genes to prognostic stratification of follicular lymphoma treated with immunochemotherapy. The study was based on 428 patients enrolled in the FOLL05 prospective trial that compared three standard-of-care regimens (rituximab-cyclophosphamide-vincristine-prednisone versus rituximabcyclophosphamide-doxorubicin-vincristine-prednisone versus rituximab-fludarabine-mitoxantrone) for the first line therapy of advanced follicular lymphoma. Polymorphisms were genotyped on peripheral blood DNA samples. The primary endpoint was time to treatment failure. Polymorphisms of FCGR2A and FCGR3A, which have been suggested to influence the activity of rituximab as a single agent, did not affect time to treatment failure in the pooled analysis of the three FOLL05 treatment arms that combined rituximab with chemotherapy (P=0.742, P=0.252, respectively). These results were consistent even when the analysis was conducted by intention to treat, indicating that different chemotherapy regimens and loads did not interact differentially with the FCGR2A and FCGR3A genotypes. The genotype of MLH1, which regulates the genotoxic effect of doxorubicin, significantly affected time to treatment failure in patients in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone arm (P=0.001; q
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U2 - 10.3324/haematol.2014.108183
DO - 10.3324/haematol.2014.108183
M3 - Article
C2 - 25596266
AN - SCOPUS:84926319479
SN - 0390-6078
VL - 100
SP - 517
EP - 524
JO - Haematologica
JF - Haematologica
IS - 4
ER -