The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin: FIL-FOLL study

Davide Rossi, Alessio Bruscaggin, Piera La Cava, Sara Galimberti, Elena Ciabatti, Stefano Luminari, Luigi Rigacci, Alessandra Tucci, Alessandro Pulsoni, Giovanni Bertoldero, Daniele Vallisa, Chiara Rusconi, Michele Spina, Luca Arcaini, Francesco Angrilli, Caterina Stelitano, Francesco Merli, Gianluca Gaidano, Massimo Federico, Giuseppe A. Palumbo

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Abstract

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 FCreceptor, 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

Original languageEnglish
Pages (from-to)517-524
Number of pages8
JournalHaematologica
Volume100
Issue number4
DOIs
Publication statusPublished - 2015

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Follicular Lymphoma
Doxorubicin
Genotype
Vincristine
Prednisone
Treatment Failure
Cyclophosphamide
Drug Therapy
Mitoxantrone
Standard of Care
DNA Repair
Biomarkers
Rituximab
DNA
Therapeutics
Genes
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Rossi, D., Bruscaggin, A., La Cava, P., Galimberti, S., Ciabatti, E., Luminari, S., ... Palumbo, G. A. (2015). The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin: FIL-FOLL study. Haematologica, 100(4), 517-524. https://doi.org/10.3324/haematol.2014.108183

The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin : FIL-FOLL study. / Rossi, Davide; Bruscaggin, Alessio; La Cava, Piera; Galimberti, Sara; Ciabatti, Elena; Luminari, Stefano; Rigacci, Luigi; Tucci, Alessandra; Pulsoni, Alessandro; Bertoldero, Giovanni; Vallisa, Daniele; Rusconi, Chiara; Spina, Michele; Arcaini, Luca; Angrilli, Francesco; Stelitano, Caterina; Merli, Francesco; Gaidano, Gianluca; Federico, Massimo; Palumbo, Giuseppe A.

In: Haematologica, Vol. 100, No. 4, 2015, p. 517-524.

Research output: Contribution to journalArticle

Rossi, D, Bruscaggin, A, La Cava, P, Galimberti, S, Ciabatti, E, Luminari, S, Rigacci, L, Tucci, A, Pulsoni, A, Bertoldero, G, Vallisa, D, Rusconi, C, Spina, M, Arcaini, L, Angrilli, F, Stelitano, C, Merli, F, Gaidano, G, Federico, M & Palumbo, GA 2015, 'The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin: FIL-FOLL study', Haematologica, vol. 100, no. 4, pp. 517-524. https://doi.org/10.3324/haematol.2014.108183
Rossi, Davide ; Bruscaggin, Alessio ; La Cava, Piera ; Galimberti, Sara ; Ciabatti, Elena ; Luminari, Stefano ; Rigacci, Luigi ; Tucci, Alessandra ; Pulsoni, Alessandro ; Bertoldero, Giovanni ; Vallisa, Daniele ; Rusconi, Chiara ; Spina, Michele ; Arcaini, Luca ; Angrilli, Francesco ; Stelitano, Caterina ; Merli, Francesco ; Gaidano, Gianluca ; Federico, Massimo ; Palumbo, Giuseppe A. / The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin : FIL-FOLL study. In: Haematologica. 2015 ; Vol. 100, No. 4. pp. 517-524.
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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 FCreceptor, 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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