Q&A: Pharmacists Play Key Role as Epcoritamab Moves Into Second-Line Therapy for FL

In an interview with Pharmacy Times®, Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, a clinical pharmacy manager at the University of Kansas Health System, discussed key findings from the global phase 3 EPCORE FL-1 trial (NCT05409066), which led to the FDA approval of epcoritamab (Epkinly; Genmab, AbbVie) in combination with rituximab (Rituxan; Genentech) and lenalidomide (Revlimid; Bristol Myers Squibb) (R²) for patients with relapsed or refractory follicular lymphoma (RR FL).

Mahmoudjafari emphasizes the central role of pharmacists in implementing this therapy, from coordinating step-up dosing and monitoring cytopenias or immune-mediated toxicities to managing infection prophylaxis and assisting with financial navigation. She also notes that this approval may accelerate the development of bispecific antibody strategies and their use in earlier lines of therapy across follicular and other indolent lymphomas, further expanding accessible, immune-based treatment options.

Pharmacy Times: Can you summarize the key findings of the EPCORE FL-1 trial that supported the FDA’s approval of epcoritamab in combination with lenalidomide and rituximab for patients with relapsed/refractory follicular lymphoma?

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: The EPCORE FL-1 trial was a global, phase 3, open-label randomized trial that compared epcoritamab plus rituximab and lenalidomide. We often refer to rituximab and lenalidomide as R². That combination plus epcoritamab was compared against R² alone in patients with relapsed or refractory follicular lymphoma.

These patients had to have grade 1 to 3A disease after at least 1 prior systemic therapy, including an anti-CD20 agent plus chemotherapy. They were randomized 1:1, so they either received epcoritamab plus R² or R² alone. Epcoritamab was given using standard subcutaneous step-up dosing up to 48 mg in cycle 1, then weekly in cycles 2 and 3, and every 4 weeks beyond that for up to 12 cycles. For primary endpoints, overall response rate was the main focus, with progression-free survival as another key measure. Secondary endpoints included complete response rate, duration of response, and overall survival—endpoints we commonly see in this disease state.

What was remarkable is that the combination of the three drugs led to a significantly higher overall response rate in patients receiving epcoritamab plus R² compared with R² alone—95% versus 79%. R² has a strong response on its own, but epcoritamab with R² performs even better. The risk of progression or death was reduced by 79% with the addition of epcoritamab. Progression-free survival also favored the combination, and complete response rates and durability were substantially higher. The median duration of response was not yet reached, which is encouraging.

Regarding safety, some cytokine release syndrome (CRS) was observed, typically early and mostly grade 1 or 2, and manageable with standard mitigation strategies. No new safety signals were identified beyond what was previously known. Overall, this shows a high and durable response rate in previously treated patients, with mostly low-grade CRS that is manageable—highlighting a promising chemo-free, immunotherapy-based regimen for relapsed/refractory follicular lymphoma.

Pharmacy Times: How does the mechanism of action of epcoritamab as a bispecific T-cell engager differ from traditional therapies used in follicular lymphoma?

Mahmoudjafari: Epcoritamab is unique. It's considered chemotherapy-free. It’s a CD3xCD20 bispecific T-cell engager that simultaneously binds CD20 on malignant B cells and CD3 on T cells. Essentially, it redirects a patient’s own T cells to directly kill the lymphoma cells. This differs fundamentally from traditional follicular lymphoma therapies, which rely on passive immune mechanisms or cytotoxic chemotherapy. Compared with lenalidomide alone, epcoritamab provides more direct, targeted action, leading to potent, antigen-specific cytotoxicity without the ex vivo cell manipulation required for CAR T-cell therapy. So it’s a unique mechanism of action and clearly shows strong responses in this patient population.

Pharmacy Times: Following the FDA’s approval, where does the epcoritamab plus rituximab and lenalidomide regimen fit within the current treatment paradigm for relapsed/refractory FL?

Mahmoudjafari: This was recently approved in November 2025 by the FDA in combination with rituximab and lenalidomide for adult patients with relapsed/refractory follicular lymphoma after at least 1 prior systemic therapy. In terms of landscape implications, this is the first bispecific antibody combination regimen in a randomized phase 3 trial to demonstrate superior outcomes versus standard R². The magnitude of progression-free survival advantage, deep complete response rates, and durability suggest this could become a new benchmark in second-line therapy. It’s an important early option for patients who have progressed after frontline immunochemotherapy and are candidates for an immune-based outpatient regimen.

It may be particularly attractive for patients looking to avoid chemotherapy-related toxicities, those who aren’t ideal candidates for CAR T-cell therapy, or those who prefer a readily available off-the-shelf option with strong efficacy. The challenge isn’t with epcoritamab itself, but lenalidomide can be toxic, so pharmacists need to be mindful of management considerations for these patients.

Pharmacy Times: What practical considerations should pharmacists keep in mind when helping clinicians and patients implement this regimen in practice?

Mahmoudjafari: Pharmacists play a central role in implementing any new FDA-approved regimen, especially bispecific antibodies. Pharmacists must coordinate to ensure patients receive their step-up dosing, whether inpatient, outpatient, or a combination. They also ensure the care team follows mitigation protocols. Often pharmacists help create these protocols and make sure adherence is maintained while educating patients and caregivers. Pharmacists are critical in selecting premedications and managing prophylaxis, particularly because this regimen can be immunosuppressive. Patients often require prophylactic antibiotics, and pharmacists help monitor and prevent infections.

With lenalidomide, cytopenias are common, so pharmacists manage these and other immune-mediated toxicities. Pharmacists also support financial navigation, helping patients afford therapy and get insurance approval. In short, pharmacists have key operational, clinical, and financial responsibilities in implementing this regimen safely and effectively.

Pharmacy Times: From a patient perspective, what improvements does this approval offer compared with existing standard options in terms of outcomes and quality of life?

Mahmoudjafari: From a patient perspective, this approval offers high response rates without traditional chemotherapy, which some patients are hesitant to pursue. It’s convenient and off-the-shelf, so patients don’t have to worry about cell collection and manufacturing over several weeks. Patients also avoid prolonged hospitalizations often seen with CAR T-cell therapy. There’s potential for improved quality of life, as many patients can maintain daily activities and work while receiving outpatient treatment. Overall, this regimen allows faster access to effective therapy at the first relapse.

Pharmacy Times: How do you think the approval of a bispecific antibody combination will influence future therapeutic development in follicular lymphoma or other indolent lymphomas?

Mahmoudjafari: This approval validates bispecific antibodies as a cornerstone platform in indolent lymphomas and beyond. Many bispecifics are being studied in hematologic malignancies and other areas of oncology. We can anticipate accelerated development of combination strategies, movement into earlier lines of therapy, and continued exploration to maximize efficacy. The focus remains on chemo-free, immune-based regimens that are scalable and accessible to the broader community.