Treatment tailoring by optimized early residual disease assessment in classic Hodgkin lymphoma
Davide Rossi
PhD, MDFoundation for the Institute of Oncology Research (IOR)
Project Term: July 1, 2019 - June 30, 2022
Incorporation of circulating tumor DNA (ctDNA) monitoring into clinical trials of classic Hodgkin lymphoma (cHL), which is the primary objective of this proposal, will allow to: i) precisely define ctDNA accuracy in anticipating disease course; and ii) test if ctDNA results can be used to guide treatment decisions. The project results can translate ctDNA monitoring as a routine response assessment tool for cHL.
Classic-Hodgkin lymphoma (cHL) is the second most common type of aggressive lymphoma, a tumor of the lymphocytes, affecting 8200 new cases every year in the US. Despite the progressive reduction of the death rates over the years, an unmet medical need in cHL is the early and accurate identification of chemorefractory patients (10-20%), as they are candidates for treatment intensification to maximize the chances of cure, as well as the early and accurate identification of good-risk patients (80-90%), as they are candidates for treatment de-escalation to avoid both short and long-term complications of chemo-radiotherapy. Positron emission tomography–computed tomography (better known as PET) is a nuclear medicine imaging technique that allows to check for residual tumor cells after cHL treatment. Despite widely used to guide treatment decisions, PET has a 20-30% false positive rate, which may expose a significant fraction of cHL patients to over-treatment and its complications. Liquid biopsy is a highly sensitive test done on a sample of blood to look for pieces of DNA from tumor cells that are circulating in the blood. Persistence of DNA from tumor cells in blood despite therapy anticipates chemoresistance, while clearance of blood from tumor DNA anticipates cure. In this project, liquid biopsy will be used in combination with PET to find out at an early time point of treatment (i.e. after 2 cycles of chemotherapy) how well therapy is working in cHL patients, and if treatment intensification can be effectively and safely administered solely to patients who turned out to have residual disease confirmed by both PET and liquid biopsy. If successful, the project has the chance of providing an innovative, reliable, non-invasive and radiation-free tool (i.e. liquid biopsy) for improving the monitoring of treatment activity and the amount of residual disease during therapy in cHL patients. The most immediate impact of the project may be the incorporation of the liquid biopsy in the forthcoming international guidelines for lymphoma staging and restaging. Also, better anticipation of disease cure or relapse by the liquid biopsy may ultimately allow to spare over-treatment among those patients whose residual disease is inaccurately estimated by interim PET.