Exploring the Approval of Epcoritamab for Diffuse Large B-Cell Lymphoma With Reid Merryman, MD

Oncology Data Advisor: Welcome to Oncology Data Advisor, I'm Keira Smith. Today, I'm joined by Dr. Reid Merryman from Dana-Farber Cancer Institute, who is a primary investigator of the EPCORE NHL-1 trial that recently led to the approval of epcoritamab for diffuse large B-cell lymphoma.

Dr. Merryman, thank you so much for joining today. To start off, would you like to introduce yourself and share what your work focuses on?

Reid Merryman, MD: My name's Reid Merryman. I'm one of the lymphoma doctors at Dana-Farber. I'm a Clinical Investigator with an interest in immunotherapies for lymphoma patients.

Oncology Data Advisor: Great, thank you so much for coming on today to talk about this approval with us.

Dr. Merryman: My pleasure.

Oncology Data Advisor: For some background, what makes DLBCL a challenging disease to treat?

Dr. Merryman: Diffuse large B-cell lymphoma is one of the most common lymphoma subtypes. It's diagnosed in about 25,000 patients in the US each year. We can cure most patients with initial therapy, probably about 65%, but if patients aren't cured, treatment becomes more challenging.

Fortunately, we now have chimeric antigen receptor (CAR) T-cell therapies, which are curative for a minority of patients. But for patients who either are not eligible for CAR T-cell therapy or who relapse after CAR T-cell therapy, we have limited options. We have a few new treatments that were approved over the last three years, but they're palliative for the most part and often are not associated with long remission. So, we really need new therapies, particularly for that multiply-relapsed patient population. It's an area of unmet need.

Oncology Data Advisor: Definitely. Since you were one of the investigators of the EPCORE NHL-1 trial that led to the approval of epcoritamab for this disease, what were some of the efficacy results and the biggest highlights that led to the approval?

Dr. Merryman: The phase 2 trial that led to the approval of epcoritamab enrolled about 150 patients with multiply relapsed diffuse large B-cell lymphoma. It was a heavily pretreated patient population. Patients received a median of three prior lines of therapy. About 60% of patients had primary refractory disease, and about 40% of patients had received prior CAR T-cell therapy, so it was a challenging patient population.

Even so, responses were seen in many patients. The overall response rate was 63%, and the complete response rate was 39%, both of which are very impressive numbers for this patient population. There's about a year of follow-up now, so we have some idea of what the durability of responses will be, and it looks like complete responses are particularly durable. The median duration of complete response has not been met yet. We need longer follow-up, but it may be possible that some patients will have long-term remissions with this therapy.

I think we're also seeing some encouraging numbers for patients with prior CAR T-cell therapy. These are particularly hard patients to treat, and while the response rates for the 40% of patients with prior CAR T-cell therapies were lower, the overall response rate was about 55%, and the complete response rate was about 30%. Those are still pretty good numbers for that challenging-to-treat population, and the duration of response looks similar for patients with prior CAR T-cell therapy, so I'm very excited to start using this drug in clinic.

Oncology Data Advisor: Definitely, those are very impressive results. As far as safety, are there any toxicities that clinicians should be particularly aware of to monitor for?

Dr. Merryman: Epcoritamab has a similar safety profile to the other CD3 and CD20 bispecific antibodies that are either approved or in development. The most frequent side effect that we think about is cytokine release syndrome (CRS). In this trial, that was seen in about 50% of patients. Most cases of CRS are low-grade, but a small number of patients did have grade three CRS, which is CRS that requires pressor support. That was 2.5% in this study.

Fortunately, CRS with epcoritamab seems to be predictable, in that it almost always occurs during the first two cycles. Most CRS occurs on Cycle 1, Day 15, which is the first full dose of epcoritamab. Patients were generally hospitalized on the initial clinical trials, during that first full dose when we expect to see the most cytokine release syndrome. So, that's a key toxicity that people should know about. I think with time, we'll get better at predicting which patients to worry about CRS for and which patients we maybe need to worry a little bit less about, as we have done with patients treated with CAR T-cell therapy, where cytokine release syndrome is a common side effect.

Unlike CAR T-cell therapy, we don't see a lot of neurotoxicity with bispecific antibodies, including epcoritamab. Infections are another concern. With any B-cell–depleting therapy, you worry about infections and you worry about more severe viral infections like COVID infections, so that's another thing to look out for if you're treating a patient with this drug.

Oncology Data Advisor: Absolutely, that's important to know. So, now that epcoritamab has received approval, how do you expect it to fit into the treatment landscape for DLBCL?

Dr. Merryman: I think it's a moving question because there are a number of trials that are testing epcoritamab in earlier lines of therapy. But right now, based on its current approval, I think this will be my go-to medication for many patients who are ineligible for CAR T cells or who relapse after CAR T-cell therapy. I suspect, like I said at the beginning, that's an area of unmet need. We have many patients who are left without many good treatment options, so I think epcoritamab will be used in those populations.

Oncology Data Advisor: Definitely. Well, this is a very exciting approval for this disease, so thank you so much for coming on today to talk about it.

Dr. Merryman: Of course.

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.

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