Amongst sufferers with relapsed/refractory follicular lymphoma, fixed-duration Epkinly (epcoritamab) plus Rituxan (rituximab) and Revlimid (lenalidomide; R2) was related to important enhancements in progression-free survival (PFS) and response charges in contrast with R2 alone.
Findings from the section 3 EPCORE FL-1 trial have been offered in a press briefing through the 2025 American Society of Hematology (ASH) Annual Assembly and Exposition.
At a median follow-up of 14.8 months, outcomes confirmed that the median PFS per unbiased evaluate committee (IRC) was not estimable with Epkinly plus R2 in contrast with 11.7 months with R2 alone, resulting in a 79% discount within the threat of illness development or demise. The concordance charge was 94% for PFS between IRC and investigator evaluation. The estimated 16-month PFS charges have been 85.5% and 40.2%, respectively.
Glossary
Development-Free Survival (PFS): The size of time throughout and after remedy that the most cancers doesn’t develop or worsen.
Goal Response Price (ORR): The proportion of sufferers whose most cancers shrinks or disappears with remedy. It consists of each full and partial responses.
Full Response (CR) Price: The proportion of sufferers whose most cancers fully disappears on checks after remedy.
Partial Response (PR) Price: The proportion of sufferers whose most cancers shrinks considerably—however doesn’t disappear fully—after remedy.
Steady Illness (SD): When the most cancers doesn’t shrink sufficient to be referred to as a response but in addition doesn’t develop or unfold. It stays “steady.”
Progressive Illness (PD): When the most cancers grows or spreads regardless of remedy.
General Survival (OS): How lengthy sufferers keep alive after analysis or the beginning of remedy, it doesn’t matter what occurs with the most cancers.
Neutropenia: A low variety of neutrophils, an vital white blood cell that fights an infection. Neutropenia will increase the chance of infections and is a typical facet impact of some therapies.
Cytokine Launch Syndrome (CRS): A response that may occur when sure therapies activate the immune system very strongly. It will possibly trigger fever, tiredness, and low blood stress. Medical doctors monitor and deal with CRS rigorously.
Thrombocytopenia: A low variety of platelets, the blood cells that assist cease bleeding. This will result in straightforward bruising, nosebleeds, or bleeding that takes longer to cease.
Pyrexia: The medical phrase for fever—when the physique temperature is larger than regular.
Febrile Neutropenia: A mix of fever and neutropenia (low infection-fighting white cells). That is handled as an emergency as a result of the physique could not be capable of struggle infections nicely.
The Epkinly routine elicited a 95% goal response charge (ORR) in contrast with 79% with R2 alone. Within the Epkinly arm, the whole response (CR) charge was 83% and the partial response (PR) charge was 12%; one affected person had steady illness (SD), 3% of sufferers had progressive illness (PD) and a couple of% weren’t evaluable. Within the R2 arm, the CR charge was 50% and the PR charge was 29%; 7% of sufferers every had SD, PD and weren’t evaluable.
“[Epkinly] and R2 is a novel chemotherapy-free, fixed-duration remedy that’s appropriate for outpatient administration, and we consider units a brand new benchmark as customary of look after second-line [and beyond] follicular lymphoma,” lead research creator Dr. Lorenzo Falchi of the Lymphoma Service at Memorial Sloan Kettering Most cancers Middle in New York stated within the oral presentation. “We’re completely satisfied to see that the FDA granted full approval to [Epkinly] and R2 on Nov. 18, 2025, for [this patient population].”
R2 is the one second-line different to chemoimmunotherapy-based remedy for sufferers with relapsed/refractory follicular lymphoma. The FDA initially authorised Epkinly, a CD3xCD20 bispecific antibody, as a single agent for the remedy of sufferers with relapsed/refractory follicular lymphoma following not less than two strains of systemic remedy.
Early information from the section 1b/2 EPCORE NHL-2 trial, which evaluated fixed-duration Epkinly plus R2 for relapsed/refractory follicular lymphoma, demonstrated deep and sturdy responses and a manageable security profile.
In November 2025, the FDA additionally authorised Epkinly together with R2 in relapsed/refractory follicular lymphoma, primarily based on the section 3 EPCORE FL-1 findings, which is what Falchi offered through the press briefing. Within the worldwide, open-label, EPCORE FL-1 trial, sufferers underwent randomization to obtain fixed-duration Epkinly at 48 milligrams (mg) plus R2 (243 sufferers) or R2 alone (245 sufferers).
Epkinly was administered in a three-step-up, two-dosing schedule at 0.16 mg on day 1, 0.8 mg on day 8 and three mg on day 15, all in cycle 1. Cycles 2 and three have been administered weekly, and cycles 4 to 12 have been administered each 4 weeks. Rituxan was given at 375 mg/m2 for 5 cycles; the agent was given weekly in cycle 1 and each 4 weeks in cycles 2 by way of 5. Lastly, Revlimid was given at 20 mg for 12 cycles; remedy was given each day in cycles 1 by way of 12 on days 1 by way of 21.
The info cutoff date was Might 24, 2025, and sufferers have been enrolled between October 2022 and January 2025.
Baseline traits confirmed that the median age was 61 years and 40% of sufferers have been not less than 65 years outdated; 57% of sufferers have been male and 72% have been White. Thirty-one % of sufferers had an ECOG efficiency standing of 1 to 2, whereas 83% had Ann Arbor stage 3 to 4 illness. Relating to Follicular Lymphoma Worldwide Prognostic Index, the breakdown of scores was 0 to 1 (24%), 2 (32%) and three to five (44%). Twenty-two % of sufferers had cumbersome illness, consisting of not less than 7 cm.
The median time from preliminary analysis to randomization was 5 years, and the median variety of prior strains of remedy was one, with most sufferers receiving one (59%), two (24%) or not less than three (17%). All sufferers acquired a previous anti-CD20 antibody and three% had acquired prior R2. Forty-one % of sufferers skilled illness development inside two years from beginning frontline remedy; 34% of sufferers have been refractory to their first-line remedy, and 37% of sufferers had double-refractory illness.
Further efficacy information confirmed that the median DOR with Epkinly plus R2 was NE in contrast with 11.5 months with R2 alone.
The Epkinly routine additionally prolonged time to subsequent lymphoma remedy (TTNLT); the median was NE (NE-NE) in contrast with 24.3 months with R2 alone. At 16 months, 92.8% of sufferers on Epkinly plus R2 remained free from new anti-lymphoma remedy versus 64.9% of these on R2 alone.
Falchi famous there’s a constructive development for OS with the Epkinly arm, which is NE in each arms, including that there are 10 and 25 occasions within the Epkinly and R2-alone arms, respectively. Sixteen-month estimates for OS have been 95.8% for Epkinly plus R2 versus 88.8% with R2 alone.
Relating to security, any-grade unwanted effects occurred in 100% and 99% of sufferers on Epkinly plus R2 and R2 alone, with grade 3 (extreme) or larger unwanted effects at 90% and 68%, respectively. Severe unwanted effects occurred in 56% and 29%, respectively, and unwanted effects that led to remedy discontinuation occurred in 19% and 12% of sufferers.
Any-grade and grade 3 or larger unwanted effects of scientific curiosity occurring in not less than 20% of sufferers on Epkinly/R2 and R2 alone included infections (77% and 33% versus 53% and 16%), neutropenia (74% and 69% versus 52% and 42%), cytokine launch syndrome (any-grade, 35% versus <1%) thrombocytopenia (28% and 9% versus 18% and 6%), pyrexia (24% and <1%; 14% and 1%), rash (24% and eight% versus 22% and 4%) and COVID-19 (22% and three% vs 13% and a couple of%).
On the Epkinly arm, 3% of sufferers discontinued attributable to neutropenia versus 2% within the R2-alone arm. Febrile neutropenia occurred in 6% and three% of sufferers, respectively. Discontinuation charges attributable to infections occurred in 6% and 1% of sufferers, respectively.
Two % and 4% of sufferers on Epkinly and R2 and R2 alone skilled deadly unwanted effects. “Regardless of these larger charges of [side effects] within the Epkinly and R2 arm, the median relative dose depth was larger than 90%,” Falchi added.
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References
- “Main section 3 outcomes from the EPCORE- FL-1 trial of epcoritamab with rituximab and lenalidomide (R2) versus R2 for relapsed or refractory follicular lymphoma” by Dr. Lorenzo Falchi et al., Blood.
- “Epcoritamab, lenalidomide, and rituximab versus lenalidomide and rituximab for relapsed/refractory follicular lymphoma (EPCORE FL-1): a worldwide, open-label, randomised, section 3 trial,” by Dr. Lorenzo Falchi et al., Lancet.
- “EPKINLY™ (epcoritamab-bysp) injection prescribing data,” FDA; https://tinyurl.com/mrvfmaur
- “Fastened-duration epcoritamab plus R2 drives favorable outcomes in relapsed or refractory follicular lymphoma” by Dr. Lorenzo Falchi et al., Blood.
- “FDA approves epcoritamab-bysp for follicular lymphoma indications,” information launch, FDA; https://tinyurl.com/y8t4hh3a
