The main goal of therapy for aggressive B-cell lymphomas such as diffuse large B cell lymphoma (DLBCL) is to achieve a complete response (CR) and a definitive lymphoma free survival. In the post-rituximab era the standard immuno-chemotherapy, (rituximab cyclophophamide doxorubicin vincristina prednisone (R-CHOP), may cure about 60% of patients, but the remaining patients who experienced refractory/ relapsed disease have a dismal prognosis. Instrumental imaging tests such as computed tomography (CT) and positron emission tomography (PET) are the international standard tools to assess the response and for monitoring the disease relapse after therapy. However these approaches are limited by risk of radiation, cost and a lack of tumor specificity. High-throughput next-generation sequencing (NGS)-based assays can detect and quantify small amounts of circulating tumor DNA (ctDNA) before, during and after the treatment for DLBCL. Molecular monitoring of ctDNA could be considered as a promising non-invasive tool with immediate clinical impact on monitoring for relapse after therapy prior to clinical symptoms. ctDNA needs to be investigated as a tool to monitor minimal residual disease (MRD) for aggressive B cell lymphomas, where the monitoring of MRD is currently lacking because of the absence of circulating tumor cells. The aim of our project is to evaluate the feasibility of MRD monitoring on ct-DNA by NGS/droplet digital PCR in a prospective series of DLBCL patients treated in our institute. MRD assessment will be performed at different time points: at baseline, during and after the treatment and during the follow up.
PB molecular monitoring of ctDNA holds emerging promises that may ultimately transform our ability to monitor disease in aggressive B-cell lymphomas. This project has a potentially relevant impact at the scientific and clinical levels. The scientific significance is to apply innovative tools and high throughput technologies to generate a better knowledge of the molecular response determining the disease course.
The results of the project may be translated into clinical applications for DLBCL decision making: to provide proof of concepts on the efficacy of MRD in DLBCL as a new potential tool to direct treatment intensification in high-risk patients (according to IPI) or treatment consolidation in low-risk patients, beside PET/CT assessment of response.
Undoubtedly, future studies to investigate whether monitoring of ctDNA in the context of clinical trials can be used to improve clinical outcomes for patients with DLBCL are warranted.