Circulating Tumor DNA and Prediction of Early Progression in Follicular Lymphoma

Margarita Sánchez-Beato, IIS Puerta de Hierro-Segovia de Arana, Madrid, Spain, shares research on the monitoring of circulating tumor DNA as predictive of response to treatment and early progression among patients with follicular lymphoma.

Transcript:

Hi, I am Margarita Sánchez-Beato and I am the leader of the Lymphoma Group at the Health Research Institute of Hospital Puerta de Hierro in Madrid, Spain. I want to share with you the result of our last paper publishing clinical results entitled “Monitoring of Circulating Tumor DNA Response to Treatment and Early Progression in Follicular Lymphoma.”

This study was promoted by the Spanish Oncology Collaborative Group for the Study and Treatment of Lymphoma. As you know, follicular lymphoma is one of the most frequent non-Hodgkin lymphomas, and is also considered an indolent lymphoma. In fact, this is not a curable disease and its clinical course is quite heterogeneous.

Around 20% of the patients suffer early disease progression within 2 years of diagnosis, or transformation to a more aggressive lymphoma. And these events are associated with worse clinical outcomes, and quite shorter overall survival. Patients, in fact, with this early progression, after 5 years, have an overall survival probability of less than 50%, whereas the others that do not progress, the probability increases to more than 90%. Therefore, it's important to know as soon as possible, the patients with higher risk of progression. And in our study with circulating tumor DNA, we wanted to demonstrate if this ctDNA could help clinicians to identify these patients.

Previously, several studies in different kind of tumors have shown that circulating tumor DNA level is associated with tumor volume. And it has been useful for detecting minimal residual disease (MRD) in several tumors, as I said, including lymphomas. But mainly, it has been demonstrated in aggressive lymphoma.

However, very few studies have analyzed ctDNA in indolent lymphoma types, such as follicular lymphoma. Therefore, we decide to perform a study with a series of patients recruited prospectively and evaluate the usefulness of ctDNA.

The oncologists of the group enrolled patients from 2017, more or less, to 2022 in 8 different Spanish hospitals and collected their peripheral blood at diagnosis, during treatment, at the end of treatment, and during the follow-up. In this study, we treated a lot of the first patients, or the first 39 patients, and most of them have been treated with rituximab and [bendamustine], or rituximab and CHOP [(cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone)].

We collected the plasma samples, more than 100 samples, and perform targeted deep-sequencing analysis in this periphery DNA, and also in the genomic DNA from the tissue diagnostic biopsy samples.

Our most exciting finding was the strong association between the levels of ctDNA in this basal plasma samples with the clinical course. The number of alterations in this basal CT periphery DNA in patients who later suffered progression or did not achieve complete response, was significantly higher than in patients with better clinical course.

In addition, the monitoring of dynamic analysis of the plasma periphery DNA also showed interesting results. In fact, treated patients, all the treated patients, were able to diminish dramatically the levels of periphery DNA in plasma. But the patients with better clinical outcomes cleared up almost completely the tumoral ctDNA from the blood. But in the patients that afterwards progressed or did not respond to treatment, we can still detect the ctDNA in the blood.

The relevance of this study is that although this has been shown previously in aggressive lymphoma, this is the first one published which demonstrates the value of ctDNA in an indolent lymphoma, in follicular lymphoma, using sequencing, not only in samples before treatment but also during the follow-up of the patients.

In fact, a couple of months after our study was published, another Spanish group published a paper on lymphoma similar to our paper — similar results with a different approach — confirming this value of ctDNA analysis in indolent lymphoma.

The take-home message is that we demonstrate that [basal ctDNA] levels are associated with response and with a risk of early progression. And we suggest, we propose, that the measurement of ctDNA at diagnostics and follow-up is a valuable tool that eventually should be a routine in clinical trials and in daily clinical practice.

We are conscious that there is much work to do, but this is an exciting field with a huge potential and we expect wonderful results in the future. Thank you for your attention.

Source:

Fernández-Miranda I, Pedrosa L, Llanos M, et al. Monitoring of Circulating Tumor DNA Predicts Response to Treatment and Early Progression in Follicular Lymphoma: Results of a Prospective Pilot Study. Clin Can Research. 2022;29(1):209-220. doi:https://doi.org/10.1158/1078-0432.ccr-22-1654