Full Data Published Showing 87% CR at 3 Years for Epcoritamab Plus BR in First-Line FL

After 3 years, 87% of patients with follicular lymphoma (FL) treated from the start with epcoritamab (Epkinly; AbbVie/Genmab), bendamustine, and rituximab (BR), maintained a complete response, according to long-term results of an arm of the EPCORE-NHL-2 trial (NCT04663347) published this week.¹

Led by Umberto Vitolo, MD, of Candiolo Cancer Institute, and Lorenzo Falchi, MD, of Memorial Sloan Kettering Cancer Center, the report in HemaSphere contains 3-year follow-up data from arm 3 of the phase 1b/2 EPCORE NHL-2 trial evaluating subcutaneous epcoritamab—a CD3×CD20 bispecific antibody—combined with BR as first-line therapy for follicular lymphoma (FL).¹ The findings illuminate results presented in a poster at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition, using the same April 9, 2025, data cutoff but now in peer-reviewed form with fuller detail.²

Rationale and Design

BR is a standard first-line regimen in FL, but the authors note that “maintaining durable remissions remains challenging.” Epcoritamab is already approved as monotherapy for relapsed/refractory FL after 2 or more prior lines and in combination with rituximab plus lenalidomide (R²) after at least 1 prior line.³ Preclinical work cited in the paper found that epcoritamab and rituximab do not interfere with each other's tumor-killing activity despite both targeting CD20, and that epcoritamab “enhances rituximab-mediated cytotoxicity,” providing rationale for combining it with BR.

In arm 3, 25 treatment-naïve patients with CD20+ FL (grade 1–3A) received epcoritamab plus BR for 6 cycles of 28 days each, followed by epcoritamab monotherapy for up to 2 years. Epcoritamab was dosed subcutaneously using a step-up schedule (0.16 mg, then 0.8 mg) in cycle 1, followed by full 48 mg doses weekly through cycle 3, every 2 weeks through cycle 9, and every 4 weeks from cycle 10 onward. Bendamustine (90 mg/m²) was given on days 1–2 and rituximab (375 mg/m²) on day 1 of cycles 1–6. This was a high-risk population: all patients had Ann Arbor stage III/IV disease, 56% had a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3–5, 28% had bulky disease (≥7 cm), and 48% had bone marrow involvement.

Efficacy Results

At a median follow-up of 41.3 months, response rates remained exceptionally high. The authors report “the best overall response and CR rates were both 96%,” with a median time to complete response (CR) of 1.5 (range 1–6) months, reflecting the first scheduled response assessment. Notably, the CR rate and overall response rate (ORR) at the end of epcoritamab plus BR treatment was 96%, “which matches the best ORR,” the authors stated, indicating responses were achieved early and largely sustained through the initial combination phase.

Durability at 3 years was a key finding, the authors wrote. “At 3 years, 87% of responders maintained CR,” and this held up across difficult-to-treat subgroups. “High CR rates were observed across subgroups, including 100% of patients with bulky disease (≥7 cm), 93% with Follicular Lymphoma International Prognostic Index score ≥3, and 100% with bone marrow involvement.” Among 11 patients who completed the full 2 years of protocol treatment, all had CR at end of treatment, and 82% maintained it at data cutoff.

Longer-term survival outcomes were similarly strong: “The 3-year progression-free survival and overall survival rates were 83% and 96%, respectively.” Only 3 patients (12%) experienced disease progression within 24 months—a subgroup historically associated with poor prognosis—and these were the only patients requiring subsequent antilymphoma therapy during the study.

The authors compare these results favorably against historical BR data: a retrospective analysis across 18 US cancer centers found that “CR rates were 72% in patients with grade 1–2 FL and 66% in patients with grade 3A FL, with estimated 3-year PFS rates of 75% and 65%, respectively.” The results also track closely with a separate EPCORE NHL-2 arm combining epcoritamab with R² in first-line FL, which demonstrated a CR rate of 88% and a 3-year PFS estimate of 83%.

“These findings support the benefit of incorporating epcoritamab as a potential new backbone that would be flexibly deployed with different agent combinations in frontline FL,” the authors wrote.

Safety

All 25 patients experienced at least 1 treatment-emergent adverse event (TEAE). The authors emphasize, “The most common TEAEs in this study were hematologic and infectious in nature, aligning with the known profiles of bendamustine- and [bispecific antibody]-containing regimens.” The most frequent events included COVID-19 (84%), cytokine release syndrome (CRS, 68%), nausea (64%), injection-site reactions (56%), fatigue (52%), and neutropenia (52%). Grade 3 or higher TEAEs occurred in 92% of patients, driven largely by serious infection (44%) and neutropenia (40%).

Of note, all CRS events were low-grade (grade 1–2) and resolved, and the authors report that “no high-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome events." No clinical tumor lysis syndrome was observed.

Infection was the dominant adverse event, occurring in 92% of patients, with COVID-19 the most common at 84%. The trial's enrollment period overlapped substantially with the COVID-19 pandemic, and the authors report 1 death due to COVID-19, and 7 patients discontinued due to AEs of COVID-19. They also flag opportunistic infections of note: 1 case of progressive multifocal leukoencephalopathy, 1 P. jirovecii infection, and 2 cases of CMV reactivations, of which 1 was CMV colitis, which they attribute to the combined B-cell-depleting effects of epcoritamab and the immunosuppressive activity of bendamustine. Four patients developed secondary primary malignancies (2 basal cell carcinoma, 1 Bowen's disease, 1 cutaneous T-cell lymphoma).

Despite this toxicity burden, treatment delivery was largely preserved, they stated. "The addition of epcoritamab to BR did not impact the dose intensity of BR, and the majority of patients were able to complete the planned number of BR cycles," with median relative dose intensities of 99% to100% across all 3 agents during the combination phase.

 Discussion and Limitations

The authors conclude that epcoritamab plus BR resulted in deep, durable responses beyond 3 years with a consistent safety profile, and that these results compare favorably with BR alone, although they require confirmation in further studies. They explicitly caution that this was “a nonrandomized, single-arm study” with a small sample size, thus limiting definitive comparative conclusions and subgroup interpretation. Given bendamustine's toxicity profile, the authors advise that “physicians should carefully consider which patients are most likely to benefit from this combination.” Additional first-line FL studies incorporating epcoritamab—including chemotherapy-free and doublet approaches—are currently underway.

References

1. Vitolo U, Falchi L, Andersson P-O, et al. First-line treatment with epcoritamab in combination with bendamustine plus rituximab induces sustained remissions beyond 3 years in patients with follicular lymphoma. HemaSphere. 2026;10:e70443. Published online August 4, 2026. https://doi.org/10.1002/hem3.70443
2. Vitolo U, Falchi L, Snauwaert S, et al. Fixed-duration epcoritamab in combination with bendamustine + Rituximab (BR) for 􀀀rst-line (1L) treatment of follicular lymphoma (FL): 3-year results from EPCORE NHL-2 arm 3 demonstrate deep and durable responses with manageable safety. Blood. 2025;146(Suppl 1):5357-5358.
3. Caffrey M. Epcoritamab with rituximab plus lenalidomide approved for R/R follicular lymphoma in second line. AJMC. November 18, 2025. Accessed August 6, 2026.https://www.ajmc.com/view/epcoritamab-with-rituximab-plus-lenalidomide-approved-for-r-r-follicular-lymphoma-in-second-line