Bispecific Antibody Expands Reach to Follicular Lymphoma

The FDA approved the immunotherapy epcoritamab-bysp for certain patients with follicular lymphoma. 

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to epcoritamab-bysp (Epkinly) for the treatment of adult patients with follicular lymphoma that has relapsed after or has not responded to at least two lines of previous systemic therapy. 

Epcoritamab-bysp is a bispecific T-cell engager, a type of immunotherapy that helps bring T cells and cancer cells together so the former can fight the latter. Epcoritamab-bysp binds to the protein CD20 on B cells, the cell type from which follicular lymphoma arises, and to the protein CD3 on T cells. 

Epcoritamab-bysp is now approved to treat some follicular lymphomas, similar to the one shown here.

This is the second FDA approval for epcoritamab-bysp. It was previously granted accelerated approval to treat some adult patients with high-grade B-cell lymphoma or a subtype of diffuse large B-cell lymphoma known as “not otherwise specified.” 

The current approval was based on results from the open-label, multicohort, multicenter, single-arm, phase I/II EPCORE NHL-1 trial. The trial included patients with follicular lymphoma that had not responded to or had relapsed following at least two prior lines of systemic therapy. Responses were observed in 82% of patients, and complete responses were observed in approximately 60% of patients. The estimated median duration of response was not reached after a median of 14.8 months of follow-up; 68.4% of patients were estimated to still be responding after 12 months. 

A separate cohort included 86 patients who were treated on a dosing schedule designed to mitigate cytokine release syndrome. This regimen was selected as the recommended dose schedule for epcoritamab-bysp, which increases as follows in cycles lasting 28 days: 

  • Cycle 1: 0.16 mg on day 1, 0.8 mg on day 8, 3 mg on day 15, and 48 mg on day 22 
  • Cycles 2 and 3: 48 mg on days 1, 8, 15, and 22 
  • Cycles 4 through 9: 48 mg on days 1 and 15 
  • Cycles 10 and beyond: 48 mg on day 1 

The prescribing information for epcoritamab-bysp includes a boxed warning for cytokine release syndrome and immune effector cell-associated neurotoxicity, two serious or potentially fatal conditions associated with overactivation of the immune system. 

Follicular lymphoma is a slow-growing type of non-Hodgkin lymphoma that occurs when abnormal B cells form clumps in lymph nodes or other lymphatic tissue. According to federal statistics, approximately 2.5 people per 100,000 are diagnosed with follicular lymphoma and 0.4 people per 100,000 die of the disease each year in the United States. 

The FDA rendered its decision on June 26, 2024. Accelerated approval means that continued approval may be contingent upon a confirmatory trial.