A fixed-duration combination of epcoritamab-bysp and lenalidomide has demonstrated a statistically significant improvement in progression-free survival (PFS) in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to topline findings from the phase 3 EPCORE DLBCL-4 trial.
The combination reduced the risk of disease progression or death by approximately 60% under US censoring rules and by 56% under censoring rules used outside the United States compared with R-GemOx.
DLBCL is an aggressive B-cell malignancy and the most common form of non-Hodgkin lymphoma, representing approximately 25% to 30% of all non-Hodgkin lymphoma cases worldwide.
Although frontline immunochemotherapy may produce durable remissions, a significant number of patients experience disease that relapses or does not respond adequately to initial treatment.
Treatment selection after relapse is guided by the timing of disease progression, prior therapies, eligibility for autologous stem cell transplantation (ASCT) or chimeric antigen receptor (CAR) T-cell therapy, comorbidities, and the patient’s ability to tolerate additional chemotherapy.
Epcoritamab is a subcutaneously administered IgG1-bispecific antibody that simultaneously binds CD3 on T cells and CD20 on malignant B cells, redirecting and activating T cells to eliminate CD20-positive cells.
Lenalidomide is an oral immunomodulatory therapy with multiple antineoplastic effects, including immune-cell activation and disruption of signaling that supports malignant cell survival.
Combining lenalidomide with a T-cell–engaging bispecific antibody may augment immune activity against lymphoma cells while avoiding conventional cytotoxic chemotherapy, which can be beneficial for patients who need to manage their health and treatment side effects.
The EPCORE DLBCL-4 trial is a global, randomized, open-label, multicenter phase 3 trial evaluating fixed-duration subcutaneous epcoritamab plus lenalidomide against R-GemOx in adults with relapsed or refractory large B-cell lymphoma.
However, Genmab did not disclose detailed rates of adverse events, treatment discontinuations, cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), infections, cytopenias, response rates, overall survival (OS), or median PFS in the topline announcement.
If supported by the complete trial findings and ultimately authorized by regulatory agencies, fixed-duration epcoritamab plus lenalidomide may provide a nonchemotherapy alternative for patients with relapsed or refractory DLBCL who cannot proceed to transplantation or CAR T-cell therapy, which can help them receive necessary care at home.
According to the FDA, epcoritamab carries boxed warnings for CRS and ICANS, as well as warnings for serious infections and cytopenias.
Until complete EPCORE DLBCL-4 findings are available, the magnitude and durability of response, comparative safety, effects on quality of life, and OS benefit remain important unanswered considerations.
Genmab and AbbVie stated that they plan to discuss the findings with global regulatory authorities, as noted on the Genmab website, to help patients control their condition through proper treatment and care.
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