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Utilizing ctDNA to Assess Survival With Odronextamab for FL and DLBCL With Jon Arnason, MD

At the 2023 American Society of Hematology (ASH) Annual Meeting, Oncology Data Advisor sat down with Jon Arnason, MD, a Lymphoma Clinical Trial Specialist at Beth Israel Deaconess Medical Center, to discuss his abstract and presentation regarding the ELM-2 trial which studied circulating tumor DNA (ctDNA) as a predictive biomarker with odronextamab for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).  

Oncology Data Advisor: Welcome to Oncology Data Advisor, I'm Keira Smith. Today, I'm joined by Dr. Arnason. Thanks so much for coming on today.

Jon Arnason, MD: Hi, thanks for having me.

Oncology Data Advisor: To start off, would you like to introduce yourself and share what your work focuses on?

Dr. Arnason: My name is Jon Arnason. I'm a Lymphoma Clinical Trial Specialist at Beth Israel Deaconess Medical Center. Our focus is trying to bring new therapies for patients, with a particular interest in cellular and immune interventions.

Oncology Data Advisor: Great. So, today we're talking about your study on ctDNA as a predictive biomarker for patient outcomes in the ELM-2 trial of odronextamab. To start off, would you give us a brief overview of the ELM-2 trial and odronextamab?

Dr. Arnason: Odronextamab is a CD3 by CD20 bispecific antibody that recruits T-cell activation against CD20-expressing B-cell malignancies. We saw significant efficacy in the ELM-1 phase 1 clinical trial. ELM-2 is the evolution of that, looking at the use of odronextamab in a phase 2 experience in both diffuse large B-cell lymphoma and follicular lymphoma, with significant responses in both patient populations.

Oncology Data Advisor: Would you like to tell us about ctDNA as a background, how it was used in the trial, as well as how it's been used in FL and DLBCL in the past?

Dr. Arnason: So, we have multiple different tools for assessing response in non-Hodgkin lymphoma (NHL). The most basic is our clinical exam—you can see regressions clinically. Traditionally, we like to see a radiographic response with a positron emission tomography (PET) scan, where avidity improves to a point where you no longer believe that you have a malignancy. But ctDNA has the potential to be an additive tool or potentially a replacement for traditional imaging. The idea behind ctDNA is that for a given malignancy, there are a certain percentage of cells that are spontaneously going through apoptosis and lysis. When that occurs, they release the DNA that is intracellular into the bloodstream. By using next-generation technologies, we can detect and measure the amount of cell-free or ctDNA from the malignancy.

Oncology Data Advisor: Great. What were the results of the ctDNA analysis for this trial, and how was it associated with survival?

Dr. Arnason: We were really excited to see that for both diffuse large B-cell lymphoma and follicular lymphoma, for those patients who had the first clinical assessment—which was after four cycles and 15 days of treatment—we were able to see that those patients who were ctDNA-negative for both diffuse large B-cell lymphoma and follicular lymphoma had improved progression-free survival.

Oncology Data Advisor: Awesome. In light of these results, how do you think that ctDNA will be used in FL and DLBCL going forward?

Dr. Arnason: So, I think this is an open question. I think that one of the themes that I've seen at ASH this year is trying to answer exactly that question of, "How do we use these new technologies to best manage our patients?" I think that in the case of bispecific antibodies, there are a couple of important conclusions from this study. The first is that we are able to achieve a ctDNA minimal residual disease (MRD)–negative state with bispecific antibodies. I think that the question of durability related to this type of treatment remains open. And I think that long-term remissions are going to be predicated on achieving a ctDNA-negative response.

So, I think just that finding by itself is really important. One of the other open questions related to bispecific antibodies is duration of treatment. I think that ctDNA negativity could be a good marker by which we, in the future, with clinical trial designs trying to answer this question, we could use that as a way to have a fixed duration of bispecific antibodies. And I think ultimately, ctDNA is a good non-invasive way to monitor for relapse and allow us to get interventions in before patients have clinical disease.

Oncology Data Advisor: Great. Anything else you'd like to mention about your research?

Dr. Arnason: What I've been saying to my colleagues is that every year this meeting gets bigger and more expansive., and the rate of discovery is so incredible. So it's just really an honor to be involved with some of the moving pieces.

Oncology Data Advisor: Absolutely. Well, thanks so much for stopping by today to talk about this. It was great to hear your research, and we look forward to hearing more as everything progresses as well.

Dr. Arnason: Great. Thanks so much.

About Dr. Arnason

Jon Arnason, MD, is a Lymphoma Clinical Trial Specialist at Beth Israel Deaconess Medical Center, in Boston, Massachusetts. Dr. Arnason's clinical and research interests involve lymphomas, cellular therapies, immunotherapy, CAR T-cell therapy, and bone marrow transplant services. He is actively involved in studies to help discover and implement new up-to-date therapies for patients.

For More Information

Arnason J, Brouwer-Visser J, Luminari S, et al (2023). Circulating tumor DNA analysis associates with progression-free survival (PFS) with odronextamab monotherapy in relapsed/refractory (R/R) follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL): identification of minimal residual disease status and high-risk subgroups from the phase 2 ELM-2 study. Presented at: 2023 American Society of Hematology Annual Meeting. Abstract 427. Available at: https://ash.confex.com/ash/2023/webprogram/Paper179812.html

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor. 


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