Interest of Individual Biomarkers From the Identification of Tumor Genotype by High-throughput Molecular Techniques

Overview

Lymphomas are the most common haemopathic malignancy. The 3 most common types are diffuse large B-cell lymphoma (DLBCL), Hodgkin's lymphoma (HL) and follicular lymphoma (FL). In these three subtypes, the treatment strategy is most often curative. The therapeutic strategy is guided by PET (positron emission tomography), which optimises the risk-benefit balance between the efficacy and toxicity of the treatment and makes it possible to limit the intensity of treatment for good responders and to intensify the treatment of poor responders with a worse prognosis. PET therefore plays a central role in the pre-therapeutic evaluation of the disease and in the assessment of response to treatment. However, other complementary approaches could improve characterization prior to initiating lymphoma t-treatment and individual patient management during treatment and beyond. In DLBCL, it has been shown that the risk of relapse of good and bad responders is decreased by combining the PET response with a reduction in the amount of tumor DNA (ctDNA) in the blood, i.e. the genetic program of lymphoma cells that circulates freely in the blood. This evaluation of ctDNA has been made possible by the development of innovative techniques such as Next Generation Sequencing (NGS). In lymphomas, several approaches have been developed, the most sensitive and promising being CAPP-Seq (CAncer Personalized Profiling by deep Sequencing) developed at Stanford University. It is therefore useful to study the description of ctDNA in the 3 types of lymphomas and to analyse the progression profiles under treatment by trying to establish the major potential usefulness of these techniques: modifying treatment in case of poor response based on ctDNA +/- and PET, detecting relapses earlier than at present in patients without any other sign of relapse (clinical, blood or PET). The project presented here aims to build a collection of plasma samples taken before treatment, during treatment and during the first 2 years of follow-up in patients with one of the 3 most frequent types of lymphoma and undergoing curative treatment. The hypothesis is that sequential evaluation of ctDNA could improve the individualized management of future patients based on the results generated by the analyses of patients in this cohort. Given the progress made in setting up this tool for DLBCL and HL, it is highly appropriate to explore its potential usefulness in other subtypes such as mantle cell lymphoma (MCL) and T-cell lymphoma (TL).