Epkinly Plus Chemo Elicits Durable Responses in DLBCL

At the 2025 ASH Annual Meeting, CURE sat down for an interview with researcher Dr. Josh Brody to discuss the findings of a clinical trial which found that the combination of Epkinly (epcoritamab) with the chemotherapies gemcitabine plus oxaliplatin (GemOx) achieved durable remissions of longer than two years among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in the second-line setting.

Brody runs the lymphoma therapy program at the Icahn School of Medicine at Mount Sinai in New York.

Transcript

For patients with DLBCL, what unmet need do you hope to address by combining Epkinly with GemOx?

We're very lucky for diffuse large B-cell lymphoma that we are able to cure a majority of people with frontline therapy. That's great news. We probably cure 55%, 60% of people with standard chemoimmunotherapy. So that is great news if you're one of those 60 people. And for the other 40, there is still a lot of unmet need.

And one thing that's a big deal in that second line of therapies is CAR-T cells. Still, the majority of Americans who might be able to get CAR-T cell therapy in the second line, just for usually logistical or practical reasons, are not able to get it, and there are a lot of hurdles to getting CAR-T cells. Stem cell transplant is also a thing as a second line therapy, that's based on PARMA data from 1994, that's the old trial. The benefits of stem cell transplant compared to the side effects is a tough call with all these modern therapies. The goal of this new, more modern, off-the-shelf immunotherapy approach, combining a bispecific antibody, [Epkinly], in this case, a CD20xCD3 bispecific antibody.

So to explain what that is, it grabs the lymphoma cells and grabs your immune cells, your T cells, and makes your immune cells kill your lymphoma cells. So, an elegant concept. They have a lot of data on this and diffuse large B-cell lymphoma and others. But even though they're pretty good as monotherapy, these bispecific antibodies, they should be better with standard-of-care therapy. So combining that immunotherapy with standard chemotherapy, we saw the complete remission rates were drastically improved compared to chemo alone, and also a lot higher than the immunotherapy alone. Complete remission rates in this [Epkinly]/GemOx study that we're presenting here were about 60%, that's like 25% with chemo, or maybe 40% with the immunotherapy, shooting up to 60%. The majority of people are getting complete remissions, and these are people for whom multiple other medicines (aggressive chemotherapies, or even CAR-T) have failed. So, to get that high efficacy was great.

The medicines were, overall, well tolerated. I don't want to oversell the chemotherapy, in and of itself it has some side effects, risks of low immune system, risks of infections; but overall, they were well tolerated, and adding the immunotherapy only made a little bit of increase in the side effects. A lot of extra bang, just for a little bit extra buck overall. These were gratifying results for our patients with later-line DLBCL.

Transcript has been edited for clarity and conciseness.

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