Phase 3 Data: Epcoritamab Plus R-CHOP Lowers Risk of Progression or Death by Half in Newly Diagnosed DLBCL

Patients recently diagnosed with an aggressive form of lymphoma may soon gain a new first-line treatment option. On October 5, Genmab and AbbVie announced that incorporating the drug epcoritamab into standard R-CHOP chemotherapy reduced the risk of cancer progression or death by 51% in a large Phase 3 trial involving patients with diffuse large B-cell lymphoma, or DLBCL.

These are topline results announced by the companies, not yet a published study. Complete data, including survival figures and detailed safety profiles, have not been released or peer-reviewed, and the combination is not currently approved for newly diagnosed patients.

The finding stands out because R-CHOP has been the backbone of first-line DLBCL care since a landmark trial established it as a standard nearly 25 years ago. While many patients achieve a cure, a meaningful portion experience cancer recurrence or fail to respond fully.

EPCORE DLBCL-2 Trial Results So Far

The global EPCORE DLBCL-2 trial enrolled patients with newly diagnosed DLBCL and an International Prognostic Index (IPI) score of 2 to 5, a measure of higher-risk disease, according to the Genmab announcement. Participants were randomly assigned to receive either six cycles of epcoritamab plus R-CHOP followed by two cycles of epcoritamab, or six cycles of R-CHOP followed by two cycles of rituximab.

In the primary analyzed group, patients with the highest-risk scores of 3 to 5 showed a hazard ratio for progression or death of 0.49. The same 51% risk reduction appeared in the broader group with scores of 2 to 5, a key secondary measure, according to OncLive. The trial enrolled adults ages 18 to 79, and the main result was evaluated by an independent review committee.

The companies described the combination as “generally well tolerated and consistent with the previously reported safety profiles of the individual agents,” but did not release specific side effect rates. Epcoritamab, a bispecific antibody administered via subcutaneous injection, is already approved in the U.S. as Epkinly for certain patients whose DLBCL or follicular lymphoma returned or did not respond to earlier treatment, including in combination for follicular lymphoma. The drug carries a boxed warning for cytokine release syndrome, an immune reaction that can cause fever and low blood pressure, as well as neurologic toxicity.

Evidence Check: Strong Signal, Missing Details

The trial was randomized, a robust design, and its primary endpoint was assessed by independent reviewers, features that add weight to the result.

However, significant gaps remain. The trial was open-label, meaning patients and doctors knew which treatment was assigned. Progression-free survival measures how long cancer stays in check rather than how long patients live, and no overall survival data were shared. The announcement also failed to disclose how many patients enrolled.

The most prominent outside voice so far is not fully independent. Dr. Gilles Salles, chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center in New York, was a trial investigator and has financial interests related to AbbVie and Genmab, as the companies disclosed. He stated the results “have the potential to be practice-changing.” The public materials released so far include no comment from lymphoma specialists unaffiliated with the trial, another reason to treat the findings as preliminary.

Many prior attempts to improve upon R-CHOP have failed in Phase 3, although the FDA approved polatuzumab vedotin plus R-CHP for previously untreated DLBCL in 2023. Physicians are likely to wait for the full dataset before changing practice. Key details still missing include enrollment numbers, follow-up duration, the frequency of serious immune reactions, and whether older patients benefited as much as younger ones.

Patients and Families Weighing First-Line Options

About 25,000 people in the U.S. are diagnosed with DLBCL each year, according to figures cited by Genmab. It is the most common type of non-Hodgkin lymphoma and occurs more frequently in older adults.

Symptoms prompting a diagnosis often include painless swelling of lymph nodes in the neck, armpit, or groin, unexplained fever, drenching night sweats, weight loss, and fatigue. Individuals whose symptoms persist for more than a couple of weeks should consult a clinician.

For patients diagnosed currently, approved first-line regimens remain the standard and are often curative, and nobody should delay treatment while waiting for new drugs. Patients can ask their oncologist whether a clinical trial is appropriate for them; the federal ClinicalTrials.gov registry lists details for this study.

Cost and access could become issues later. Bispecific antibodies are expensive and often require monitoring for immune reactions, especially early in treatment, which may be difficult for patients far from major cancer centers. Patients facing high bills can inquire about manufacturer assistance programs and nonprofit support from groups such as Blood Cancer United, formerly the Leukemia & Lymphoma Society.

Genmab and AbbVie said they will submit the data for presentation at a future medical meeting and engage with regulators worldwide to determine next steps.

Key Questions Answered

What did the trial find? Adding epcoritamab to R-CHOP reduced the risk of cancer progression or death by 51% compared with R-CHOP followed by rituximab in newly diagnosed DLBCL.

Are these results final? No. They are topline results from the companies, and full data have not been presented or peer-reviewed.

Is the combination available now? Not for newly diagnosed patients. Epcoritamab is approved only for certain relapsed or treatment-resistant lymphomas.

Did the treatment help people live longer? Survival data have not been released, so that remains unknown.

What are the main side effects? Specific rates were not disclosed. Epcoritamab carries a boxed warning for cytokine release syndrome and neurologic toxicity.

What should newly diagnosed patients do? Start recommended treatment without delay and ask an oncologist whether a clinical trial is an option.

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