Study of gene polymorphisms as predictors of treatment efficacy and toxicity in patients with indolent non-Hodgkin lymphomas and mantle-cell lymphoma receiving bendamustine and rituximab

Introduction: indolent non-Hodgkin lymphomas (iNHL) and mantle-cell lymphoma (MCL) have a heterogeneous behavior, impacted by biological and clinical parameters. Bendamustine is widely used in association with rituximab (BR) to treat iNHL and MCL. The variability in treatment efficacy and toxicity could be related to germline single nucleotide polymorphisms (SNPs) in immune and inflammatory response genes. Methods: we would like to show a possible association between SNPs and treatment outcome in iNHL and MCL patients receiving BR regimen. We have investigated some SNPs that have already been associated with NHL outcome. All samples were genotyped for the IL-2 (rs2069762), IL-10 (rs1800890, rs10494879), VEGFA (rs3025039), IL-8 (rs4073), CFH (rs1065489) and MTHFR (rs1801131) SNPs by allelic discrimination assays using TaqMan SNP Genotyping Assays. Results: we have enrolled 70 patients that received rituximab 375mg/m2 and bendamustine 90mg/m2 every 28 days both as 1st line treatment (53/70) and as ≥ 2nd line regimen (17/70). Overall response rate was 97.1% (CR rate 73.9%). Relevant treatment toxicity included grade 3-4 neutropenia (24/70 patients), infections (21/70 patients; 1/70 grade ≥3), skin rash (26/70 patients; 2/70 grade ≥3). After a median follow-up of 24 months we did not report any correlation between analyzed SNPs, CR rate and PFS. However, we demonstrated an association between SNP in IL-2 (rs2069762) and the onset of skin rash (p=.0001). Conclusion: we confirm treatment efficacy and manageable toxicity of BR for iNHL and MCL patients. Our study suggests a possible role for cytokine SNPs in bendamustine-related toxicity, that could represent a promising research field.