The Genotype of MLH1 Is An Independent Predictor of Outcome In Diffuse Large B-Cell Lymphoma Treated with R-CHOP: a Training-Validation Study

• Published in: Blood 2010-11, Vol.116 (21), p.992-992
• Main Authors: Rossi, Davide, Rasi, Silvia, Di Rocco, Alice, Fabbri, Alberto, Forconi, Francesco, Bruscaggin, Alessio, Franceschetti, Silvia, Fangazio, Marco, De Paoli, Lorenzo, Bruna, Riccardo, Capello, Daniela, Chiappella, Annalisa, Bodoni, Chiara Lobetti, Giachelia, Manuela, Tisi, Maria Chiara, Pogliani, Enrico M., Lauria, Francesco, Ladetto, Marco, Hohaus, Stefan, Martelli, Maurizio, Vitolo, Umberto, Foà, Robin, Gaidano, Gianluca
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V116.21.992.992

Abstract 992 Several drugs utilized in diffuse large B cell lymphoma (DLBCL) rely on DNA damage for tumor killing. This study aimed at verifying whether single nucleotide polymorphisms (SNPs) of genes involved in DNA repair may contribute to prognostication of DLBCL treated with R-CHOP. The study utilized a training-validation design. The training cohort (n=163) was a mono-institutional, prospectively collected, consecutive series of DLBCL homogeneously treated with the same chemotherapeutic regimen both at diagnosis (R-CHOP21) and at relapse/progression (R-DHAP ± BEAM conditioned autologous stem cell transplant, ASCT). The validation cohort (n=156) was a multi-institutional retrospective series of DLBCL treated with R-CHOP at diagnosis. Candidate SNPs (n=35) were selected by an educated guess approach, and included SNPs belonging to genes involved in: i) mismatch repair (MLH1); ii) base excision repair (XRCC1, OGG1); iii) nucleotide excision repair (ERCC1, ERCC2, ERCC4, ERCC5, ERCC6, XPA, XPC); iv) double strand break repair (BRCA1, BRCA2, LIG4, XRCC2, XRCC3, XRCC4, XRCC6); and v) direct reversal (MGMT). Clinical endpoints were progression free survival (PFS) after R-CHOP, overall survival (OS) from diagnosis, and OS from salvage treatment. Univariate analysis controlled for multiple comparisons identified MLH1 rs1799977 as the sole SNP predicting DLBCL OS in the training series (AG/GG genotype: HR: 3.23; 4-year OS: 55.5% vs AA genotype: 4-year OS: 80.9%; p