Genetic Variants, Treatment Response in B-Cell Lymphoma Investigated
Evidence of inherited genetics contributing to response in patients receiving immunochemotherapy for diffuse large B-cell lymphoma.
Evidence is available of inherited genetics contributing to the response achieved in patients receiving immunochemotherapy for diffuse large B-cell lymphoma (DLBCL), according to an article published in the Journal of Clinical Oncology.1
Investigators performed a meta-analysis of four studies, two of which were genome-wide association studies: LNH2003B (N=540), a prospective clinical trial, and the Molecular Epidemiology Resource study (N=312), a prospective observational study.
Independent cohorts of patients from the Specialized Program of Research Excellence (N=391) and Group-Ouest-Est des Leucémies Aiguës et Maladies du Sang (GOELAMS)-075 randomized trial (N=294) were genotyped for top single-nucleotide polymorphisms (SNPs).
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The loci associated with event-free survival (EFS) were rs7712513 at loci 5q23.2 (hazard ratio (HR), 1.39; 95% CI: 1.23-1.57; P=2.08 x 10-7) and rs7765004 at loci 6q21 (HR, 1.38; 95% CI:1.22-1.58; P=7.09 x 10-7); however, genome-wide significance was not met. Investigators also observed that both rs7712513 and rs7765004 (HR, 1.49; 95% CI: 1.27-1.71; P=3.53 x 10-8 vs HR, 1.47; 95% CI: 1.27-1.71; P=5.36 x 10-12) were associated with overall survival.
After an exploratory analysis, a two-SNP risk score, independent of treatment, international prognostic index (IPI), and cell-of-origin classification, was also linked with EFS (P=1.78 x 10-12).
- Ghesquieres H, Slager SL, Jardin R, et al. Genome-wide association study of event-free survival in diffuse large B-cell lymphoma treated with immunochemotherapy [published online ahead of print October 12, 2015]. J Clin Oncol. doi: 10.1200/JCO.2014.60.2573