Epcoritamab + Lenalidomide Shows Promise For R/R DLBCL
- AbbVie and Genmab’s Phase 3 EPCORE DLBCL‑4 trial showed that the chemo‑free combination of epcoritamab plus lenalidomide significantly improved progression‑free survival compared with R‑GemOx in transplant‑ and CAR T‑ineligible relapsed/refractory DLBCL.
- “This is a very difficult patient population to treat because, without a curative treatment option for these patients, we often only get responses that last a few months before needing a new line of therapy,” Dr. Leslie Popplewell, chief of hematology at City of Hope Atlanta, tells SurvivorNet Connect.
- The regimen achieved a higher overall response rate with a safety profile consistent with known data, though full efficacy results are expected to be presented at a future scientific meeting.
- If confirmed in the full dataset, these findings could expand the role of bispecific antibodies earlier in DLBCL treatment, offering a new option for patients who lack access to curative cellular therapies.
AbbVie and Genmab have announced positive topline results from the Phase 3 EPCORE DLBCL-4 trial evaluating the chemotherapy-free combination of epcoritamab plus lenalidomide in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant and CAR T-cell therapy.
According to the company, the study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with rituximab, gemcitabine, and oxaliplatin (R-GemOx).
The regimen also met a key secondary endpoint of overall response rate, while overall survival data remain immature.
“The trial is following the trend of incorporating novel T-cell therapy earlier in the treatment of DLBCL,” Dr. Leslie Popplewell, chief of hematology at City of Hope Atlanta, tells SurvivorNet Connect. “This particular trial looks at patients who are not eligible for stem cell transplant or CAR T-cell therapy, and this is a very difficult patient population to treat because, without a curative treatment option for these patients, we often only get responses that last a few months before needing a new line of therapy.”
If confirmed in the full dataset, the findings could further expand the role of bispecific antibodies earlier in the treatment algorithm for patients who are not candidates for potentially curative cellular therapies.
The Current Data
Epcoritamab is currently approved as monotherapy for adults with R/R DLBCL after two or more prior lines of systemic therapy, and EPCORE DLBCL-4 is one of the first Phase 3 studies to report a positive outcome for a chemotherapy-free epcoritamab-based combination in the transplant and CAR T ineligible setting.
AbbVie reported that the safety profile was consistent with the known safety profiles of epcoritamab and lenalidomide, with no new safety signals identified.
The hazard ratio within the U.S. is 0.40 (95% CI 0.30–0.55), p<0.0001 — a 60% risk reduction. Outside the U.S., the hazard ratio is reported as 0.44 (95% CI 0.33–0.60), p<0.0001 — a 56% risk reduction.
Lingering Questions Remain
Several key questions remain ahead of the full presentation, including the magnitude of the PFS benefit, hazard ratio, complete response rate, duration of response, overall survival, and patient-reported outcomes.
Additional subgroup analyses, including outcomes of high-risk subsets, will help clarify which patients derive the greatest benefit.
“I look forward to the final analysis of the trial, which is still ongoing, and likely we will see a more comprehensive report at the ASH meeting in December 2026,” Dr. Popplewell explains.
Although EPCORE DLBCL-4 focused on patients who were ineligible for ASCT and CAR T-cell therapy, Dr. Popplewell notes that the positive findings also reinforce broader efforts to integrate bispecific antibodies across different treatment settings.
“It is difficult to know how we will ultimately resolve the sequencing of bispecific antibodies versus CAR T-cells,” she says. “Both are exciting new treatments that have entirely changed the way we think about treating relapsed DLBCL.”
The complete efficacy and safety results, expected to be presented later this year, will provide greater insight into whether epcoritamab plus lenalidomide should become a new standard of care for patients with relapsed or refractory DLBCL who are not candidates for transplant or CAR T-cell therapy.
