Epcoritamab-bysp (Epkinly) demonstrated exceptional durability in patients with relapsed/refractory large B-cell lymphoma (LBCL), with 96% of patients who achieved complete response at 2 years maintaining their remissions at 3 years, according to long-term follow-up data from the pivotal EPCORE NHL-1 trial presented at the 2025 ASCO Annual Meeting.
The CD3xCD20-directed bispecific T-cell engager showed remarkable persistence of benefit, with the median duration of complete response reaching 36.1 months (95% CI, 20.2-NR) and the longest ongoing complete response exceeding 43 months. Among the 32 patients who remained in complete response at 2 years, all but one achieved either partial or complete response by the second assessment at 12 weeks.
Sustained Clinical Benefit Beyond Treatment Discontinuation
The analysis revealed that patients could maintain clinical benefit even after discontinuing therapy. Among 12 patients who stopped epcoritamab for reasons other than disease progression, complete response was sustained for a median of 14 months (range, 2-28 months) after treatment cessation, with no relapses observed during this period.
"These findings underscore the benefits of treat-to-progression epcoritamab in the third-line and beyond setting, indicating that some patients obtain long-term remission," said lead study author Yasmin H. Karimi, MD, a clinical assistant professor of internal medicine in the Division of Hematology/Oncology at the University of Michigan in Ann Arbor.
Patient Characteristics and Treatment Outcomes
The post hoc analysis focused on patients who maintained complete response 2 years after initiating epcoritamab treatment. These patients demonstrated favorable baseline characteristics compared to the overall study population, including lower tumor burden with bulky disease greater than 7 cm present in only 19% versus 31% in the overall population. They also had lower lactate dehydrogenase levels (294 U/L vs 338 U/L) and baseline ferritin levels (383 μg/L vs 406 μg/L).
At a median follow-up of 37 months, patients received a median treatment duration of 35 months (range, 8-43). Eighty-one percent of patients remained on treatment at the 2-year mark, with 59% still receiving therapy at the data cutoff. The median progression-free survival and overall survival among complete responders were both not reached, with an estimated 96% and 97% of patients reported as progression-free and alive, respectively, at 3 years.
Minimal Residual Disease Assessment
Molecular response assessment showed impressive depth of remission, with 95% of evaluable patients who achieved complete response at 2 years testing negative for minimal residual disease at day 1 of cycle 13.
Safety Profile and Long-term Tolerability
The safety analysis revealed that 81% of patients experienced at least one treatment-emergent adverse event leading to dose delays. The most common adverse events throughout treatment were COVID-19 (66%), cytokine release syndrome (53%), and diarrhea (44%). After the 2-year mark, COVID-19 remained the most frequent adverse event (34%), followed by diarrhea (16%) and upper respiratory tract infection (16%).
Serious infections occurred in 19% of patients still on treatment after 2 years, with pneumonia being the most common (n=4). Two treatment-related deaths occurred after 2 years due to COVID-19 pneumonia and bacterial pneumonia.
Regulatory Status and Future Directions
Epcoritamab received FDA accelerated approval in May 2023 for patients with relapsed/refractory diffuse LBCL not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after at least 2 lines of prior therapy. The approval was based on the initial findings from EPCORE NHL-1.
The EPCORE NHL-1 study enrolled 157 patients with relapsed/refractory CD20-positive mature B-cell neoplasms, including DLBCL, double- or triple-hit DLBCL, primary mediastinal B-cell lymphoma, and high-grade B-cell lymphoma. Patients received epcoritamab subcutaneously at 48 mg until progressive disease or unacceptable toxicity, with 41% achieving complete response.
"Epcoritamab is being explored in earlier lines of therapy, including in ongoing trials for first-line and second-line DLBCL," Karimi concluded, highlighting the potential for expanding the therapeutic application of this bispecific antibody to earlier treatment settings.
