Future Directions Point to Leveraging ctDNA in Lymphoma

Reid Merryman, MD, clinical investigator and assistant professor at Dana-Farber Cancer Institute, discusses the role of minimal residual disease (MRD) in lymphoma and his presentation on the topic at the 2024 Society of Hematologic Oncology Annual Meeting.

According to Merryman, next-generation sequencing has revolutionized MRD testing in lymphoma, enabling more sensitive and comprehensive detection of circulating tumor DNA (ctDNA). This has led to increased clinical utility, with MRD-guided therapy becoming more prevalent.

He highlights that as technology continues to advance, ctDNA is expected to play a key role in optimizing lymphoma treatment and improving patient outcomes.

Transcription:

0:09 | I talked about minimal residual disease in lymphoma, which is a very big topic. So, minimal residual disease is not a new concept in lymphoma. We have had tests like flow cytometry and PCR, but they were limited to certain lymphoma subtypes that had circulating disease or stereotypical chromosomal rearrangement. But with development of next-generation sequencing, we were able to track ctDNA, circulating tumor DNA, for all lymphoma subtypes. And over the last 10 or 15 years, we have seen a trend that by tracking more tumor markers, tumor reporters, we are able to increase the sensitivity of assays.

0:49 | I talked about the evolution of assays that we have seen, starting with clonoSEQ, which is an example of immunoglobulin-based high throughput sequencing, where we track 1 or maybe a few tumor reporters, and then panel-based assays like CAP-Seq or the AVENIO assay, where we are tracking often dozens of tumor reporters, and then the most recent ctDNA assays like PhasED-Seq or whole genome sequencing-based assays where we are tracking hundreds, or even in some cases, 1000s of tumor reporters. With each of those steps, we have seen increased sensitivity. So, there is a lot of excitement now, but using these very sensitive MRD tests to help guide therapy. We are seeing some of the first MRD-guided trials where we are actually changing therapy based on MRD results in lymphoma.

1:36 | One example is in mantle cell lymphoma, there is a phase 3 trial, which guides consolidation with transplant based on MRD status. We are also seeing trials in large cell lymphoma that are guiding intensification of frontline treatment based on interim MRD status. And then I talked about how ctDNA can be used for goals other than enumeration of MRD, so we can actually learn about the biology of a tumor based on a plasma sample. There are some exciting data looking at identifying lymphoma subgroups based on ctDNA so you can identify the LymphGen classification among patients with diffuse large B-cell lymphoma with similar results seen from plasma and tissue, similar results for Hodgkin lymphoma, which is a tough one to analyze using tissue because of the rarity of tumor cells.

2:25 | And then there is some exciting data looking at gene expression so we can actually infer gene expression based on ctDNA, and that may help us to learn or identify patients with double hit lymphoma, or even potentially transformation of an indolent lymphoma into an aggressive lymphoma, which is clinically a very important question. So, with all these advancements, I think there is a lot of excitement about, in the future, potentially using ctDNA to help guide our therapy for our patients in the clinic, although we are not quite there yet.