Genome-wide single nucleotide polymorphism analysis identifies DNA variations predictive of R-CHOP efficacy in diffuse large B-cell lymphoma

R-CHOP standard chemotherapy is successful in about 60% of patients with diffuse large B-cell lymphoma (DLBCL). Patients who do not benefit from it, due to tumor drug resistance, have a poor prognosis. To date, the available predictive biomarkers mainly relate to prognosis. We conducted the first prospective GWAS clinical study appositely designed to identify constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 217 any stage chemonaive DLBCL patients candidate to R-CHOP were enrolled. ~800000 SNPs were analysed by the UK Biobank Axiom Array. Median age of eligible pts was 59.2 years, women were 49.7%. 45.4% of pts were in stage I-II. According to the revised IPI (R-IPI), 14.1%, 56.8% and 29.2% were in the very good (0), good (1-2) and poor (3-5) prognosis groups, respectively. 85.9% of pts obtained CR to R-CHOP. Based on the results obtained, we were able to build a seven-SNP score by summing the number of deleterious alleles from the SNPs for which highly significant associations with PFS were achieved. Wild-type patients showed a prolonged PFS compared with patients carrying 1 deleterious allele or 2+ deleterious alleles (p<0.001). When the score was applied to patients stratified according to R-IPI, wild-type patients classified as R-IPI 1-2 and R-IPI 3-5 showed a prolonged PFS compared with patients with the same respective R-IPI score carrying 1 deleterious allele or 2+ deleterious alleles (p<0.001). After a proper validation in an independent cohort of patients, the seven-SNP risk score could be proposed to select patients to whom offer a more aggressive treatment as well as an additional factor to those currently included in the R-IPI that could successfully contribute to predict response to R-CHOP. Affymetrix SNP arrays were performed on 187 constitutional DNA samples from adult DLBCL patients (two samples did not pass the quality control of genotypic data). Overall, 185 samples are provided.