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ORLANDO, Fla. — Adding epcoritamab (Epkinly) to the standard-of-care (SOC) therapy of lenalidomide (Revlimid) and rituximab (Rituxan), a combination known as R2, lowered the risk for disease progression or death by 79% in patients with relapsed or refractory follicular lymphoma (FL), a study found.
Lorenzo Falchi, MD, of Memorial Sloan Kettering Cancer Center in New York City, presented the interim results of the phase 3, randomized, open-label EPCORE FL-1 trial at the American Society of Hematology (ASH) 2025 Annual Meeting.
The overall estimated survival rate at 16 months was 95.8% in the epcoritamab plus R2 group and 88.8% in the R2 group. Overall response rates were 95% and 79%, respectively, over a median follow-up of 14.8 months, wrote Falchi and colleagues in their paper, which was published in The Lancet at the time of the presentation.
In addition to better outcomes in overall response rate and progression-free survival (PFS), patients taking epcoritamab plus R2 also had “longer duration of response, superior time to next lymphoma therapy, and a positive trend for overall survival,” Falchi said, during his presentation at the meeting. “The benefits were consistent across patient subgroups, including high-risk and low-risk patients, and the safety profile was manageable in this regimen that was administered fully in the outpatient setting.”
The FDA approved epcoritamab plus R2 on November 18 for the treatment of patients with relapsed or refractory FL. It also granted traditional approval for the treatment of relapsed or refractory FL after two or more lines of systemic therapy, following an earlier accelerated approval.
An ‘Unmet Need’ for Better Therapy
For the most part, patients with FL are not cured of their disease, Falchi explained at the meeting. “Particularly after the first-line therapy, the chance and duration of responses become shorter with each subsequent line of therapy. There clearly is an unmet need in this space.”
The R2 regimen, he added, “certainly underperforms and does not serve well in this population because most patients either do not respond or relapse.”
The study enrolled 488 participants. The subjects were randomly assigned in a 1:1 ratio to receive treatment with epcoritamab plus R2 (n = 243; median age, 60 years; 57% male; 69% White and 26% Asian) or R2 alone (n = 245; median age, 63 years; 56% male; 75% White and 22% Asian).
“The study included a number of high-risk patients, including 34% with primary refractory disease, 42% with CD20 refractory disease, and 37% of patients with double-refractory disease. That means refractory to CD20 antibodies and chemotherapy,” Falchi said.
Study Results: Response Rates, PFS, Deaths
The complete response rate was 83% for the epcoritamab plus R2 group vs 50% for the R2 group (P < 0.0001). The median duration of response was 11.5 months with R2 and not evaluable with epcoritamab plus R2.
The median PFS was not evaluable in the epcoritamab plus R2 group and was 11.7 months in the R2 group, and the estimated 16-month PFS favored epcoritamab plus R2 (85.5% vs 40.2%).
Among treated patients, deaths occurred in 4% of the epcoritamab plus R2 group vs 10% of the R2 group. Adverse events of grade 3 or higher were more common in the epcoritamab plus R2 group, with grade 3 or higher neutropenia occurring in 69% of the 243 participants receiving epcoritamab plus R2 and 42% of the 238 participants receiving R2.
“Adding epcoritamab to R2 certainly resulted in added adverse events, but these…did not lead to a significant rate of treatment discontinuation,” Falchi said. “Only 3% of patients discontinued due to neutropenia and 6% due to infections.”
The study authors noted limitations such as the open-label design and the “relatively short” follow-up time.
Study Shows ‘Gigantic Benefit’
In an interview with Medscape Medical News, hematologist oncologist Joshua Brody, MD, director of the Lymphoma Immunotherapy Program at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai in New York City, said the study shows a “gigantic benefit” for epcoritamab plus R2 in terms of PFS and a “strong trend” toward overall survival benefit.
“This should be the [SOC] for second- and later-line follicular lymphoma,” said Brody, who was not involved in the study.
As for adverse effects, he said his experience has shown that “overall, epcoritamab is very well tolerated. It’s one of the best-tolerated medicines we have. It’s not quite as gentle as rituximab but might be one of the next best things in terms of safety.”
While infections that could land patients in the hospital were more common in patients taking the triplet therapy, “those infections couldn’t have been too bad because overall, the patients were living longer with the triple therapy,” Brody said.
In an accompanying commentary to the paper published in The Lancet, Laura Magnano, MD, PhD, and Andrea Rivero, MD, of the Hematology Department at Hospital Clinic of Barcelona, IDIBAPS, Barcelona, Spain, wrote that “if confirmed with longer follow-up, fixed-duration epcoritamab plus R2 could represent an important therapeutic advancement for individuals with early relapsed follicular lymphoma, offering deeper and more durable responses than current approaches and potentially redefining the [SOC].”
The study was funded by AbbVie and Genmab.
Falchi disclosed having relationships with Roche, Genentech, Genmab, AbbVie, Innate Pharma, BeOne, AstraZeneca, Sanofi, Merck, ADC Therapeutics, Seagen, Ipsen, Johnson & Johnson, Regeneron, and Kite.
Magnano disclosed having relationships with Roche, BeOne, and Janssen. Rivero disclosed having relationships with Roche, BeOne, and Takeda.
Brody disclosed having relationships with AbbVie, Genmab, Roche, ADC Therapeutics, Epizyme, Seagen, Bristol Myers Squibb, Genentech, Kite, and Merck.
