In May 2023, EPKINLY (epcoritamab-bysp) was granted accelerated approval by the US Food and Drug Administration (FDA) for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and high-grade B-cell lymphoma after two or more lines of systemic therapy.

Recently in February 2024, the FDA granted Priority Review of the supplemental Biologics License Application (sBLA) for EPKINLY, for the treatment of adult relapsed or refractory follicular lymphoma after two or more lines of therapy with a target action date of June 2024. If approved, epcoritamab will be the first and only subcutaneous bispecific antibody to treat adults with relapsed/refractory follicular lymphoma (R/R FL) after two lines of prior therapy. This supplemental Biologics License Application was supported by data from the phase I/II EPCORE NHL-1 trial (NCT03625037) clinical trial, demonstrating strong and durable treatment responses.

During EHA 2024, Umberto Vitolo reported 1st results from EPCORE NHL-1 FL cycle 1 optimization (C1 OPT) cohort investigating mitigation strategies for cytokine release syndrome (CRS) with no mandatory hospitalization in patients with R/R FL receiving epcoritamab.

 

KOL insights

“I think overall, with time and more experience like what they've already done with rituximab, obinutuzumab or venetoclax, we will get comfortable with the unique adverse events that come with these treatments. Again, once that comfortability level is reached, I think the utilization of this bispecific and probably all the other ones may hit the mark, and it will be quite substantial. Overall, it'll help benefit the patients.” – MD, United States

Conclusion 

FL is the second most common form of NHL, accounting for 20-30% of all NHL cases, and it primarily affects B-cells. Despite being considered incurable with conventional therapies, there are several treatment options for FL. These include watchful waiting for asymptomatic patients, radiotherapy targeting the affected lymph nodes, chemotherapy to kill cancer cells, and targeted therapies specifically designed for lymphoma cells. However, FL tends to relapse, and with each relapse, the periods of remission become shorter. The impact of FL on patients is significant, affecting both emotional well-being and quality of life. The uncertainty about symptom development and the need for treatment can cause anxiety, and frequent relapses can lead to increased healthcare costs and a decline in overall well-being. Research is ongoing to improve outcomes and potentially find a cure for FL, offering hope for better management and treatment of the disease in the future.

The 3-SUD regimen and prophylactic dexamethasone administration and hydration have significantly reduced the incidence and severity of CR) and ICAN). Remarkably, most patients were monitored as outpatients, eliminating the need for mandatory hospitalization. The manageable CRS across various treatment settings is a positive outcome.

In terms of efficacy, epcoritamab demonstrated robust and clinically meaningful results in the largest dataset for R/R FL to date. Early and durable deep responses were observed, and high minimal residual disease negativity rates were achieved. Consistent efficacy was seen across both the pivotal and C1 OPT cohorts, considering response rates, MRD negativity, and time to response. Importantly, MRD negativity at any time correlated with improved progression-free survival.

These encouraging findings further support the feasibility and safety of epcoritamab as a potential outpatient treatment option for patients with R/R FL. The FDA’s grant of Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD) underscores its potential impact. 

 

Epcoritamab-bysp has a boxed warning for cytokine-release syndrome and immune effector cell–associated neurologic toxicity syndrome. It also has warnings/precautions for infections, cytopenias, and embryofetal toxicity.