Amongst older sufferers with newly identified diffuse massive B-cell lymphoma (DLBCL), remedy with fixed-duration Epkinly (epcoritamab-bysp) plus dose-attenuated Rituxan (rituximab) plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-mini-CHOP) seemed to be properly tolerated and elicited responses, scientific trial information have proven.
Information from arm 8 of the part 1/2 EPCORE NHL-2 trial, which had been offered on the 2025 ASH Annual Assembly, confirmed that at a median follow-up of 33.4 months, the general response fee (ORR) in all sufferers (28 sufferers) was 93%, which was comprised of a whole response (CR) fee of 86% and a partial response (PR) fee of seven%. The median time to response was 1.4 months and the median time to CR was 1.6 months.
At two years, 79% of sufferers remained in response to remedy with the routine, and 79% remained in CR. Of the 22 sufferers who accomplished remedy, 20 skilled a CR on the finish of remedy (91%). At a median follow-up of twenty-two.6 months after the tip of remedy, 90% of the 20 sufferers remained in CR. Furthermore, the two-year progression-free (PFS) and total survival (OS) charges had been 76% and 82%, respectively. The median PFS and OS weren’t reached regardless of Worldwide Prognostic Index rating.
Glossary
General Response Price (ORR): The proportion of sufferers whose most cancers shrinks or disappears after remedy. It consists of each partial and full responses.
Development-Free Survival (PFS): The size of time throughout and after remedy that the most cancers doesn’t develop or worsen.
General Survival (OS): How lengthy sufferers keep alive after prognosis or the beginning of remedy, no matter whether or not the most cancers returns or progresses.
Worldwide Prognostic Index (IPI) Rating: A software docs use—particularly for sure lymphomas—to estimate how aggressive the illness could also be. It considers elements similar to age, stage of most cancers, signs, and a few blood take a look at outcomes to assist information remedy planning.
Minimal Residual Illness (MRD): A really small quantity of most cancers cells that stay within the physique after remedy, even when assessments present no apparent indicators of illness. Extremely delicate assessments can detect MRD and assist docs perceive the danger of the most cancers returning.
Myocardial Infarction: The medical time period for a coronary heart assault. It occurs when blood move to a part of the center is blocked, inflicting coronary heart muscle injury.
Elevated Lactate Dehydrogenase (LDH): Greater-than-normal ranges of an enzyme discovered in lots of tissues. When LDH is elevated in blood assessments, it may be an indication of cell injury or irritation and will assist docs perceive how energetic the most cancers is.
Neutropenia: A low variety of neutrophils, a kind of white blood cell that fights an infection. Neutropenia can enhance the danger of infections and is a typical facet impact of chemotherapy.
Cytokine Launch Syndrome (CRS): An inflammatory response that may occur when sure most cancers remedies activate the immune system very strongly. Signs can embody fever, fatigue and low blood strain. Medical doctors monitor for CRS intently.
Hypokalemia: A lower-than-normal degree of potassium within the blood. Potassium helps muscle groups and nerves perform correctly. Low ranges could cause weak spot, cramps, or irregular heartbeats.
Of the 21 sufferers evaluable for minimal residual illness (MRD), 20 (95%) had been destructive on the time of the info cutoff date of Sept. 21, 2025. On the first evaluation, which was achieved on day 1 of cycle 3, 80% (16) of sufferers achieved MRD negativity. Of the 4 MRD-positive sufferers at this evaluation, three transformed to MRD negativity by the second evaluation, which was achieved on day 1 of cycle 6; two sufferers skilled subsequent progressive illness. Notably, MRD negativity was noticed throughout all affected person subgroups, together with cumbersome illness (89%) and people with an IPI rating starting from 3 to five (93%).
“We are able to conclude that together with dose-attenuated chemotherapy, [Epkinly] might have a job within the remedy of sufferers with traditionally poor outcomes,” Dr. Chan Cheah, of the Sir Charles Gairdner Hospital and the College of Western Australia, in Nedlands, Australia, stated throughout a presentation of the info.
Why add Epkinly to R-mini-CHOP?
Though R-mini-CHOP is the usual of care (SOC) for sufferers with newly identified DLBCL who aren’t in a position to obtain the complete dose, outcomes with the routine stay suboptimal, Cheah defined. “It’s clear that higher choices for these sufferers are required,” he added. Beforehand, the CD3xCD20 bispecific antibody Epkinly was discovered to be efficacious when administered as a monotherapy or paired with SOC in these with newly identified DLBCL.
For instance, findings from the part 2 EPCORE DLBCL-3 trial indicated that single-agent Epkinly induced sturdy responses in sufferers with newly identified massive B-cell lymphoma and comorbidities. Different findings from EPCORE NHL-2 confirmed that the mix of Epkinly and R-mini-CHOP elicited an ORR of 89% and a CR fee of 82% in aged sufferers with newly identified DLBCL who couldn’t obtain the complete dose of R-CHOP. On the assembly, Cheah shared follow-up information from EPCORE NHL-2.
What did EPCORE NHL-2 consider?
The open-label, part 1b/2 trial enrolled sufferers with newly identified DLBCL, which might have been DLBCL not in any other case specified, T-cell or histocyte-rich DLBCL, high-grade B-cell lymphoma, or grade 3B follicular lymphoma. Sufferers had an ECOG efficiency standing starting from 0 to 2 and couldn’t be eligible to obtain full-dose R-CHOP as a result of they had been 75 years of age or older or 65 years of age or older with a comorbidity.
Twenty-eight sufferers acquired a set length of subcutaneous Epkinly at a dose of 48 mg as soon as weekly for cycles 1 and a pair of and each three weeks for cycles 3 to six and intravenous R-mini-CHOP, which comprised 375 mg/m2 of Rituxan, 400 mg/m2 of cyclophosphamide, 25 mg/m2 of doxorubicin, 1 mg/m2 of vincristine — all given each three weeks — and 100 mg/day of prednisone, given on days 1 to five of every cycle from cycles 1 to six. Epkinly was then given at 48 mg each 4 weeks for cycles 7 to eight.
By way of baseline traits, the median affected person age was 81 years. Sufferers weren’t eligible to obtain a full dose of anthracycline due to age older than 75 years (96%), hypertension requiring remedy (54%), diabetes mellitus (11%) or historical past of myocardial infarction (4%). Furthermore, 43% of sufferers had an IPI rating of 4 to five at screening, 39% had a cumbersome tumor of seven cm or bigger, and the bulk had elevated lactate dehydrogenase (64%).
What was the protection profile of Epkinly on this inhabitants?
Cheah famous that almost all unintended effects had been gentle to average in severity, and no new security considerations related to the addition of Epkinly to R-mini-CHOP offered with longer follow-up. Probably the most frequent grade 3 (extreme) or larger treatment-emergent unintended effects had been neutropenia (43%), severe infections (32%) and anemia 14%). Most grade 3 or larger severe infections had been reported throughout the first six cycles of remedy, when R-mini-CHOP was being coadministered.
The most typical treatment-emergent facet impact was cytokine launch syndrome (CRS), which occurred in 61% of sufferers; this impact was grade 1 (gentle) for 32% of sufferers and grade 2 (average) for 29% of sufferers. Time to first onset of CRS occurred at a median of 16 days. Sufferers had been handled with both Actemra (tocilizumab; 29%) or corticosteroids (14%), resulting in CRS decision throughout all sufferers affected. The median time to decision was two days. CRS led to remedy discontinuation in a single affected person. Cheah famous that the majority (90%) CRS occasions occurred in cycle 1 of remedy.
Extra widespread treatment-emergent unintended effects occurring in 20% or extra sufferers had been neutropenia, severe infections, anemia, constipation, fatigue, hypokalemia and fall. No sufferers skilled immune effector cell–related neurotoxicity syndrome (ICANS) or tumor lysis syndrome (TLS).
TEAEs led to discontinuation of Epkinly in three sufferers (11%), together with one deadly occasion, and discontinuation of R-mini-CHOP in six sufferers (21%).
What’s the significance of the up to date EPCORE NHL-2 information?
“Regardless of an older inhabitants of newly identified diffuse massive B-cell lymphoma, the outcomes noticed in arm 8 of the EPCORE NHL-2 evaluating fixed-duration Epkinly plus R-mini-CHOP are encouraging,” Cheah acknowledged in a information launch issued by Genmab. “These outcomes, together with these from different arms of the trial, assist the potential for mixtures of Epkinly with normal of care remedy throughout a variety of illness settings and affected person populations.”
References
- “Epcoritamab + R-mini-CHOP leads to 2-year remissions and excessive MRD negativity charges in aged sufferers with newly identified DLBCL: Outcomes from the EPCORE NHL-2 trial” by Dr. Chan Cheah et al., offered at: 2025 ASH Annual Assembly; Dec. 6 to 9, 2025; Orlando, Florida. Summary 64.
- “Fastened-duration epcoritamab monotherapy induces excessive response and MRD-negativity charges in aged sufferers with newly identified massive B-cell lymphoma (LBCL) and comorbidities: Outcomes from EPCORE DLBCL-3” by Dr. Umberto Vitolo et al., offered at: 2025 ASH Annual Assembly; December 6 to 9, 2025; Orlando, Florida. Summary 63.
- “Fastened-duration epcoritamab + R-mini-CHOP in sufferers with beforehand untreated diffuse massive B-cell lymphoma ineligible for full-dose R-CHOP: Up to date outcomes from arm 8 of the Epcore NHL-2 trial,” by Dr. Chan Cheah et al. Blood. 2024;144(suppl 1):3106. doi: 10.1182/blood-2024-199652
- “Genmab proclaims information from a number of scientific trials exhibiting remedy with fixed-duration epcoritamab led to remissions in first-line diffuse massive B-cell lymphoma (DLBCL) and follicular lymphoma (FL),” information launch; https://ir.genmab.com/news-releases/news-release-details/genmab-announces-data-multiple-clinical-trials-showing-treatment
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