Epcoritamab Therapy Demonstrates Promising Outcomes for Follicular Lymphoma in Clinical Trials

Promising Clinical Results for Epcoritamab in Follicular Lymphoma

In a landmark clinical trial, AbbVie's epcoritamab (DuoBody® CD3xCD20) has emerged as a potential breakthrough treatment for adults suffering from relapsed or refractory follicular lymphoma (FL). The findings from the Phase 1b/2 EPCORE® NHL-2 trial, which were showcased during the 66th Annual Meeting and Exposition of the American Society of Hematology (ASH), present a compelling narrative for the efficacy of this innovative therapeutic approach.

Study Overview

The EPCORE NHL-2 trial was focused on examining the fixed-duration subcutaneous administration of epcoritamab in combination with lenalidomide and rituximab (R2) for adult patients diagnosed with relapsed or refractory FL. The trial enrolled 111 participants, with a median follow-up period exceeding two years. Remarkably, the overall response rate (ORR) achieved by the combination therapy stood at an impressive 96%, while the complete response (CR) rate reached 87%.

Notably, among patients who achieved a complete response after the combination therapy, an estimated 89% remained in complete response at 18 months, signifying a durable efficacy.

Clinical Implications

Dr. Mariana Cota Stirner, AbbVie's vice president and therapeutic area head for hematology, emphasized the significant advantages these findings illustrate regarding the treatment of relapsed or refractory FL. The data suggest that epcoritamab combined with standard therapies could provide a long-lasting treatment option for a patient demographic that desperately needs more effective therapies, particularly given that FL is often considered an incurable malignancy.

The Challenge of Follicular Lymphoma

FL, characterized as an indolent type of non-Hodgkin lymphoma, represents approximately 20-30% of lymphoma cases, with an estimated 15,000 new cases emerging each year in the United States. Sadly, the reality for many patients is one of continual relapse, with every recurrence typically resulting in shorter remissions until eventual transformation into a more aggressive form of lymphoma. Studies indicate that more than 25% of FL patients may experience transformation to diffuse large B-cell lymphoma, which is associated with significantly poorer survival outcomes.

Dr. Lorenzo Falchi, a lymphoma specialist from the Memorial Sloan Kettering Cancer Center, reiterated the critical need for more viable treatment options for patients who find themselves in this challenging situation. The results from the EPCORE NHL-2 trial provide hope that epcoritamab can serve as a crucial option in combination therapies.

Safety Profile and Considerations

While the clinical results are encouraging, the safety profile of epcoritamab must be thoroughly assessed. The trial highlighted that 57% of participants reported COVID-19 during the treatment course, leading to discontinuation in 13% of cases. Other common treatment-emergent adverse events included neutropenia (62% of patients) and cytokine release syndrome (CRS, affecting 51%). CRS events were primarily low grade, emerging predominantly after the initial full dose of the medication, and typically resolved without the need for treatment cessation.

It's essential to note that as of now, the combination of epcoritamab and R2 has not gained approval in the U.S., EU, or any other region, and ongoing trials will continue to explore its safety and efficacy in varied settings.

Future Directions

The regulatory journey for epcoritamab received a boost when the U.S. FDA granted breakthrough therapy designation for the medication in conjunction with lenalidomide and rituximab, aiming to treat adult patients with relapsed or refractory FL who have undergone at least one prior line of treatment. The ongoing Phase 3 EPCORE FL-1 trial is expected to provide further clarity on the efficacy of epcoritamab, potentially solidifying its role as a foundational treatment in managing B-cell malignancies.

In conclusion, the updated results from the EPCORE NHL-2 trial underscore the transformative potential of epcoritamab for relapsed or refractory FL, illustrating its high response rates and paving the way for further investigation and potential advancements in treatment strategies for this challenging condition.