The National Institute for Health and Care Excellence (NICE) has recommended epcoritamab (Tepkinly, AbbVie) as a treatment option for adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. 

Under the final draft guidance, epcoritamab can be used provided treatment is stopped after 3 years or earlier if the lymphoma progresses, and the drug is supplied under the company’s commercial arrangement with the NHS.

The recommendation is expected to benefit around 250 patients in England each year who have exhausted standard options for this incurable cancer.

Understanding Follicular Lymphoma

Follicular lymphoma is the most common type of low-grade lymphoma, affecting B lymphocytes within the immune system's lymphatic network. In England in 2022, 2404 cases were diagnosed (1217 in females and 1187 in males). The 5-year survival rate is approximately 90%, although outcomes are poorer in patients with additional risk factors or treatment-resistant disease. 

Despite its indolent course, follicular lymphoma is incurable and characterised by repeated relapses. Around 20% of patients develop more aggressive disease requiring multiple lines of therapy, and options become increasingly limited after third- or fourth-line treatment. 

Clinical experts noted that later-line options in the UK can be more limited compared with some comparable countries, particularly for patients diagnosed at a younger age who exhaust standard options. 

How the Therapy Works 

Epcoritamab is a CD3 × CD20 bispecific antibody that binds to CD20 on malignant B cells and CD3 on T cells, leading to T-cell-mediated destruction of cancer cells.

The therapy is administered subcutaneously at 48 mg doses, offering greater convenience than intravenous alternatives and allowing patients to continue working throughout treatment. A step-up dosing regimen is used during the first cycle to mitigate cytokine release syndrome; therapy begins with a 0.16-mg priming dose, followed by intermediate dosing before full-strength administration. Treatment continues for up to 3 years or until disease progression, whichever occurs first.

Superior Survival Gains

The approval was based on evidence from multiple clinical trials, including the EPCORE NHL-1 trial, a single-arm phase 2 study, and the phase 3 EPCORE FL-1 trial. 

In the EPCORE FL-1 trial, which enrolled 488 participants across 189 centres in 30 countries, epcoritamab combined with lenalidomide and rituximab showed superior efficacy over standard therapy. The combination achieved an overall response rate of 95% vs 79% with lenalidomide and rituximab alone, with complete response rates of 83% and 50%, respectively. Median progression-free survival was not reached in the epcoritamab group compared with 11.7 months in the control group, representing a 79% reduction in the risk for disease progression or risk.

The earlier EPCORE NHL-1 monotherapy study of 128 patients with multiply relapsed or refractory follicular lymphoma showed an overall response rate of 82% with a complete response rate of 62.5%.

Safety Profile

The most common grade 3-4 adverse event was neutropenia, occurring in 25% of patients receiving monotherapy. Cytokine release syndrome was reported in 65% of patients but was predominantly low-grade, with only 2% experiencing grade 3 events. Immune effector cell-associated neurotoxicity syndrome occurred in 6% of patients, all grade 1-2.

In the combination therapy trial, grade 3 or higher adverse events were more frequent with epcoritamab plus lenalidomide and with rituximab vs standard therapy alone, but adverse events were manageable and consistent with established safety profiles.

Access and Implementation

Tepkinly will be available in two vial strengths: a 4 mg/0.8 mL concentrate for solution priced at £547.33 and a 48 mg/0.8 mL solution at £6568.00, excluding VAT. 

NICE concluded that the treatment offers sufficient value to warrant routine NHS funding, which must be implemented within 90 days of final guidance publication. 

AbbVie has agreed a confidential commercial discount with the NHS, providing a potential alternative to traditional chemotherapy, which often carries a heavy side-effect burden for patients who have already undergone multiple treatment cycles.