Novel markers for determining risk and evaluation of minimal residual disease in diffuse large B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease that is usually curable with frontline immunochemotherapy and whose prognosis is directly impacted by the usual prognostic factors grouped within the International Prognostic Index (IPI). Despite the overall improvement in the outcome of patients with DLBCL since the introduction of rituximab, 40% of patients are primarily refractory or experience short-term relapse and have an extremely poor prognosis. The prognostic impact of the response to treatment as assessed by intermediate PET could be increased by combining it with the results of the modern molecular biology techniques, which include measuring the VDJ rearrangement in blood, or Next generation sequencing (NGS) of a dedicated somatic mutation panel in circulating tumor DNA, according to the concept of liquid biopsy. Emerging data has also suggested that these methods would be a powerful tool in the assessment of minimal residual disease (MRD) in DLBCL. Important questions remain about the most appropriate timing and the most efficient technique for evaluating the MRD throughout the course of the disease. We conducted a review of the recent literature to present, summarize and explain the major pilot studies that have established novel markers for determining baseline risk in DLBCL, early assessment of disease response and post-therapeutic MRD surveillance. Indeed, in the coming years, the evaluation of the MRD will be a secondary objective of all major clinical trials in this pathology, in order to confirm its clinical relevance and reproducibility, before setting up clinical trials based on the evaluation of the MRD as the primary decision-making criterion for the adaptation of patient treatment.