Investigating Epcoritamab for Follicular Lymphoma and Beyond With Reid Merryman, MD

Epcoritamab, a bispecific CD20-directed CD3 T-cell engager, is currently being investigated in numerous settings for patients with non-Hodgkin lymphomas. Recently, results were presented at the European Hematology Association (EHA) Congress for Cohorts 2A and 2B of the phase 1/2 EPCORE NHL-2 trial, which is investigating an epcoritamab combination for patients with relapsed/refractory follicular lymphoma. In this interview, Dr. Reid Merryman, an Attending Physician at Dana-Farber Cancer Center and one of the study’s investigators, discusses the significance of these results and the efficacy of epcoritamab across the various tumor types being studied.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. I’m Kera Smith, and today I’m joined by Dr. Reid Merryman. Dr. Merryman, it’s nice to talk to you again.

Reid Merryman, MD: Great to be here.

Oncology Data Advisor: So, last month, we talked about the recent approval of epcoritamab for diffuse large B-cell lymphoma (DLBCL). Recently, results were also presented for epcoritamab for follicular lymphoma. What is this trial investigating in comparison to the trial that the approval was based on?

Dr. Merryman: Epcoritamab has been tested across a number of different B-cell non-Hodgkin lymphomas, and while the epcoritamab was approved for DLBCL, we’ve also seen some very encouraging results in other lymphomas, including follicular lymphoma. At the American Society of Clinical Oncology (ASCO) Meeting and EHA Congress earlier this year, results were presented for a trial that tested epcoritamab in combination with R2—lenalidomide and rituximab. It showed very encouraging results for patients with relapsed or refractory follicular lymphoma.

Oncology Data Advisor: What were the results that were presented, and what was the efficacy of the regimen?

Dr. Merryman: This combination was tested in about 110 patients. All patients received standard dosing for R2, which was given over 12 cycles, and two different dosing strategies were used for epcoritamab. In Arm 2A and Arm 2B, there was more or less frequent epcoritamab dosing. What we saw was that in a fairly high-risk patient population—where about 60% of patients had stage IV disease, about 40% of patients had progression of disease within 24 months (POD24), and about 60% of patients had high-risk Follicular Lymphoma International Prognostic Index (FLIPI) scores—we saw high response rates. The overall response rate was 98%, and the complete response rate was 87%, both of which are quite impressive in this setting.

Notably high response rates were seen across all different patient subgroups, including those with high-risk features like those with primary refractory disease, POD24, and high-risk FLIPI scores. There’s about a year of follow-up as of this summer, and the responses seem to be durable. The one-year progression-free survival was about 80%, and the one-year duration of complete response was about 90%. Again, responses seem to be durable across different patient subgroups, including in the high-risk patient groups.

Oncology Data Advisor: Those are very impressive results. Has the efficacy of epcoritamab been relatively similar across the different tumor types that have been investigated?

Dr. Merryman: That’s a good question. This is a pattern that we see that in general; it’s easier to get responses in indolent lymphomas than it is in aggressive. The response rates for single-agent epcoritamab have been higher for follicular lymphoma compared with diffuse large B-cell lymphoma. That may also have to do with the amount of prior treatment. In this study, patients had received a median of one prior line of therapy, whereas in diffuse large B-cell lymphoma, patients had received more prior lines. In the registrational phase 2 trial, patients received three prior lines of therapy, and a higher percentage of patients had prior chimeric antigen receptor (CAR) T-cell therapy in the diffuse large B-cell lymphoma trials, so they were more heavily pretreated. But I think the data so far suggests that these drugs are particularly effective for follicular lymphoma.

Oncology Data Advisor: Great. Have any different toxicities been observed across the different populations?

Dr. Merryman: I would say that the toxicity profile looks pretty similar in the different studies. The most common side effects are cytopenias and cytokine release syndrome (CRS). The rates of CRS, if you look closely, they might be slightly different, but I think we see fairly frequent CRS occurring in approximately half of patients. Then low rates of high-grade CRS are between 0% and 5% across the different studies and across histologies. I think the pattern has been similar, too, in terms of the timing of CRS, where it’s mostly in Cycle 1 or Cycle 2. The highest frequency of CRS occurs with the first full dose of epcoritamab, which is given on Cycle 1, Day 15.

Oncology Data Advisor: I know there are several different arms or different trials of epcoritamab that are being investigated right now. Are there any additional directions or future ones that are planned, as well?

Dr. Merryman: Across the CD3/CD20 bispecifics, there are combination studies basically in every possible line of therapy, in first-line, second-line, et cetera, which I think is really exciting. We have these really potent drugs, and we don’t yet know where they will fit best in our treatment armamentarium. The approvals that we’re seeing now in the third line or later are monotherapy, but I suspect that we’ll probably see approvals in the future in combinations and in earlier lines of therapy.

Oncology Data Advisor: Any parting thoughts you’d like to share about how epcoritamab fits into the treatment landscape for these diseases?

Dr. Merryman: I think it’s really exciting that epcoritamab is now approved and that it’s a tool we have for patients. Unfortunately, patients who relapse after CAR T-cell therapy, those with diffuse large B-cell lymphoma, really have limited options. This is a great tool to have, and I’m excited to be using it in clinic.

Oncology Data Advisor: That’s very exciting. Thank you so much for taking the time to talk about it today.

Dr. Merryman: Sure, thanks for having me.

About Dr. Merryman

Reid Merryman, MD, is an Attending Physician in the Lymphoma Program at Dana-Farber Cancer Institute and an Instructor in Medicine at Harvard Medical School in Boston. He specializes in the treatment of leukemias and lymphomas, with clinical interests including autologous stem cell transplant, immunotherapy, and CAR T-cell therapy. Dr. Merryman’s research focuses on the development of immune-based therapies for patients with lymphoma.

For More Information

Sureda A, Falchi L, Leppa S, et al (2023). Epcoritamab with rituximab + lenalidomide (R2) provides durable response in patients with high-risk follicular lymphoma, regardless of POD23 status. Presented at: 2023 European Hematology Association Congress. Abstract S222.

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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