Chan Cheah, MBBS, Sir Charles Gairdner Hospital, Perth, Australia, presented updated results from the EPCORE NHL-2 trial which evaluated epcoritamab plus R-mini-CHOP among elderly, treatment-naive patients with diffuse large B-cell lymphoma (DLBCL) ineligible for full-dose anthracycline at the 2025 ASH Annual Meeting & Exposition.

At over 2 years of follow-up, the regimen achieved a 92% overall response rate, 83% complete response rate, and 2-year PFS and OS rates of 79% and 82%, respectively, with manageable toxicity. 

Dr Cheah concluded, “The efficacy results do suggest that it does suggest superior efficacy to R-mini-CHOP, but of course this would need to be tested in a randomized fashion to be confident of.”

Transcript:

My name is Chan Cheah. I'm a professor of hematology at Sir Charles Gairdner Hospital in Perth in Western Australia. I'm here at ASH and we're in Orlando. I'm presenting data at this meeting on epcoritamab plus R-mini-CHOP in patients with treatment-naive, diffuse large B-cell lymphoma unsuitable for treatment with full-dose anthracycline.

This was an arm of a larger basket trial. It was arm 8 of EPCORE NHL-2 and we treated 28 patients on this study. In order to be eligible, you needed to have treatment-naive diffuse large B-cell lymphoma and some kind of medical reason why you couldn't have full dose anthracycline. The most common reason was being over 75 years of age. We know that giving full-dose chemotherapy to this group can be challenging, or you could be over 65 years of age with significant other health issues. The median age of patients on this trial was actually 81 years, so it was a truly an elderly population.

The main reason for these patients not receiving full dose R-CHOP was actually being over 75 years of age, which was the case for 27 of the 28 patients. Other than that, other eligibility criteria included adequate organ function and performance status and no previous treatment. The treatment schedule involved the combination of chemoimmunotherapy with R-mini-CHOP. That's the standard delivery, every 3 weeks with lower doses of all of the chemotherapy components compared with full dose R-CHOP. 

In addition to that, patients received the CD20/CD3 bispecific antibody epcoritamab, which was given weekly initially for cycles 1 to 3, and then 3 weekly for cycles 3 to 6, and then monthly for cycle 7 and 8. This was a fixed duration regimen, so only 8 cycles of epcoritamab were delivered. The primary endpoint was the overall response rate with key secondary endpoints being safety, progression free, and overall survival.

We've previously presented the response rates actually, but now at this meeting, we updated the follow-up with now more than 2 years of follow-up, and the response rates remain stable. The overall response rate was 92% and the CR rate was 83%, and that was consistent across high-risk subgroups, such as high-risk IPI, bulky disease, and poor performance status. 

We also updated the progression-free and overall survival, and now we have 2-year point estimates on those with 2-year PFS 79%, 2-year overall survival, 82%. Once you get out to 2 years in diffuse large B-cell lymphoma, it's unlikely that those patients are subsequently going to experience treatment failure. We probably are looking at curing about 80% of patients treated on this study. If you compare that to historic controls, R-miniCHOP monotherapy probably only cures about 50 to 55% of patients in this similar population.

At least compared with in a non-randomized fashion, it appears as though this regimen is substantially more effective than R- miniCHOP on its own, suggesting that epcoritamab is a useful drug to add in this circumstance. Now, we, of course, did have some MRD data as well, and the majority of patients who were evaluable did attain MRD negativity. A few patients were slow to clear; they were slow to achieve molecular response. Among those patients, there was a tendency for earlier treatment failure. We did identify slow MRD clearance or failure to eradicate MRD as a potential prognostic biomarker in this setting, which is something that we've seen in other disease settings as well.

To summarize, epcoritamab plus R-miniCHOP is an applicable regimen in patients with treatment treatment-naive DLBCL. The safety profile was pretty reasonable. Cytokine release syndrome was the most common adverse event, but it was all grade 1, except for 1 case of grade 2, and the infection rate was not much more than what you would see with R-mini-CHOP alone. The efficacy results do suggest that it does suggest superior efficacy to R-mini-CHOP, but of course this would need to be tested in a randomized fashion to be confident of. Thank you for your attention.

Source:

Cheah C, Ďuraš J, Belada D, et al. Epcoritamab + R-mini-CHOP results in 2-year remissions and high MRD negativity rates in elderly patients with newly diagnosed DLBCL: Results from the EPCORE NHL-2 trial. Dec 6-9, 2025; Orlando, FL. Abstract: 64