SOHO 2024 | Using ctDNA in lymphoma: recent advances and future directions

So this morning I gave a talk about circulating tumor DNA or ctDNA in lymphoma. When we think about ctDNA, there are kind of two overlapping goals. First, to enumerate the quantity of ctDNA and second, to learn about the biology of a tumor. So I talked about a trend over the last ten years or so that newer ctDNA tests are using a higher number of tumor reporters, which increases the sensitivity of testing. I summarized data for immunoglobulin-based high throughput sequencing, or ClonoSEQ, which uses one or just a few tumor markers. I talked about panel-based approaches like CAPP-Seq or the AVENIO assay, which use a panel of disease specific mutations to track a tumor over time and thereby increase the sensitivity of the test. And I also talked about some of the newest tests, like PhasED-Seq, that use novel approaches like incorporation of phased variants to increase the number of tumor reporters and thereby increase the sensitivity of testing. I also talked about biologic characterization using ctDNA, there’s lots of really exciting data about what we can learn from ctDNA in terms of biology. So there are studies that show that we can identify subtypes of diffuse large B-cell lymphoma, LymphGen classification using plasma samples and it mirrors closely data from subtyping done using tissue, similar data for Hodgkin lymphoma where we can identify lymphoma subtypes of that disease. There’s also data suggesting that we can infer information about gene expression using circulating tumor DNA, which could be helpful in answering really important clinical questions, like whether a patient has double hit lymphoma or whether a patient with [sorry] indolent lymphoma has transformed. So in summary, there’s a lot of really exciting data about circulating tumor DNA. There are even some trials in the last few years that have started using ctDNA results to guide therapy. And I think we’ll see many more of those trials in the next few years, such that I would guess in the next five years or so in clinic, we’ll be using MRD testing, probably ctDNA, to guide therapy for many of our patients.