Treating R/R Follicular Lymphoma with Epcoritamab + Rituximab + Lenalidomide

If follicular lymphoma comes back after prior treatments (relapsed/refractory), finding therapies that are effective and long-lasting can be a challenge. 

Read about the updates on a promising treatment combination that uses epcoritamab, rituximab, and lenalidomide. 

Dr. Lorenzo Falchi's Updates from the EPCORE NHL-2 Trial

Lorenzo Falchi, MD, from Memorial Sloan Kettering Cancer Center, explained in an interview with HealthTree at the 2024 ASH conference the results of the EPCORE NHL-2 trial. This study combined a two-year combination of epcoritamab, rituximab, and lenalidomide for relapsed/refractory and high-risk patients with follicular lymphoma. 

Watch Dr. Falchi’s interview or read the summary of the research he led below.

How Effective is Epcoritamab + Rituximab + Lenalidomide for Follicular Lymphoma?

Epcoritamab (Epkinly, Genmab and AbbVie) is an FDA-approved third-line bispecific antibody for people with follicular lymphoma. Rituximab (Rituxan, Genentech) and lenalidomide (Revlimid, BMS) are a common follicular lymphoma treatment combination. 

To improve outcomes for relapsed/refractory and high-risk patients, Dr. Falchi and colleagues combined these therapies together in the EPCORE NHL-2 trial.

111 people with relapsed/refractory follicular lymphoma received the treatment combination for up to two years. 

• Epcoritamab was given as a subcutaneous injection (shot under the skin) more frequently during the first three months, then once a month for the second year.
• Rituximab was given intravenously (IV) for the first six months.
• Lenalidomide was taken as a pill for the first year.

Study Outcomes

• Encouraging responses:
  • 96% of patients responded to the therapy, meaning their tumors shrank.
  • 87% achieved a complete response, meaning no signs of follicular lymphoma were found on scans.
  • 88% of patients achieved MRD negativity (minimal residual disease testing, a highly precise method of screening remaining cancer cells in a blood sample that, if negative, confirms a deep response achieved). 
• Long-lasting benefits:
  • After nearly two years, 80% of patients remained in remission.
  • 90% of patients were alive without significant cancer progression or need for further treatment.
  • Even in cases where the lymphoma recurred, many patients didn’t need immediate treatment, as the recurrence was minimal.
• Side effects:
  • The most common side effect that 62% of patients experienced (32% of cases being severe) was neutropenia, causing symptoms like frequent infections and fever. Neutropenia is a known side effect of lenalidomide with rituximab. To reduce its impact in the trial, investigators will shorten the amount of time patients receive epcoritamab during phase 3. Patients can also expect to receive supportive care to help neutrophil counts recover.

What Do the Study’s Results Mean for People with Follicular Lymphoma? 

The results from the EPCORE NHL-2 trial are promising because they show that the combination of epcoritamab, rituximab, and lenalidomide is highly effective. Most patients in the study experienced deep, long-lasting responses to treatment, improving their quality of life.  

Specialists are further reviewing this treatment combination in phase 3 of the EPCORE FL-1 trial. Dr. Falchi hopes that with additional testing, this regimen could become the new standard of care for people with relapsed/refractory follicular lymphoma. If phase 3 results prove to be positive, they could support the approval of this combination’s use outside clinical trials. 

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Sources:

• 342 Fixed-Duration Epcoritamab + R2 Drives Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: 2-Year Follow-up from Arm 2 of the Epcore NHL-2 Trial
• Epcoritamab, Rituximab, Lenalidomide Triplet in R/R Follicular Lymphoma | Lorenzo Falchi