Analysis by TeloView® Technology Predicts the Response of Hodgkin’s Lymphoma to first line ABVD Therapy

Abstract

Classic Hodgkin’s lymphoma (cHL) is a curable cancer with disease-free survival rate of over 10 years. Over 80% of diagnosed patients respond favorably to first line chemotherapy. However, 15-20% of patients experience refractory or early relapsed disease. To date, the identification of such patients is still not possible using traditional clinical risk factors. The three-dimensional (3D) telomere analysis has been shown to be a reliable structural biomarker to quantify genomic instability, inform on disease progression, and predict patients’ response to therapy in several cancers, particularly hematological disorders. The 3D telomere analysis previously also elucidated biological mechanisms related to cHL disease progression. Here we report results of a multicenter retrospective clinical study including 156 cHL patients. We used the cohort data as a training dataset and identified significant 3D telomere parameters suitable to predict individual patient outcome at point of diagnosis. Multivariate analysis allowed for developing a predictive model using four telomeric parameters as predictors, including the proportion of t-stumps (very short telomeres). The percentage of t-stumps was the most prominent predictor to identify refractory/relapsing cHL prior to the initiation of ABVD therapy. The model characteristics include AUC of 0.83 in ROC analysis, sensitivity, and specificity of 0.8 and 0.75 respectively.