The FDA has approved epcoritamab (Epkinly, Genmab/Abbvie) with lenalidomide and rituximab (R2) for relapsed or refractory follicular lymphoma (R/R FL). 

The approval makes the T-cell-engaging bispecific antibody the first bispecific antibody approved for combination treatment in lymphoma. However, the CD19-directed cytolytic antibody tafasitamab (Monjuvi, Incyte) is also indicated with lenalidomide and rituximab for R/R FL.

Approval was based on the open-label EPCORE FL-1 trial with 488 patients randomized equally to either R2 alone, a standard of care, or with epcoritamab after a median of one prior line of systemic treatment. 

The overall response rate (ORR) was 89% with epcoritamab add-on, including 74% of subjects with complete responses; ORR was 74% with R2 with complete responses in 43%. 

Median progression-free survival (PFS) was 11.2 months in the R2 arm but not reached in the epcoritamab group (hazard ratio favoring epcoritamab 0.21, P < .0001).

By way of comparison, the 548-patient inMind trial that won tafasitamab its R/R FL indication with R2 had a median PFS of 22.4 months with tafasitamab add-on vs 13.9 months with R2 alone.

FDA also converted epcoritamab’s 2024 accelerated approval as monotherapy for R/R FL after two or more lines of systemic therapy to a full approval based on the EPCORE FL-1 results. Another bispecific antibody, mosunetuzemab (Lunsumio, Roche), carries the same indication. Tafasitamab and mosunetuzemab are both intravenous medications while epcoritamab is subcutaneous. 

Epcoritamab labeling warns that it can cause cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), with additional warnings and precautions for infections and cytopenias. Serious adverse events occurred in 51% of epcoritamab patients in EPCORE FL-1, including serious infections in 28%. CRS occurred in 24% of patients, including serious CRS in 12%. ICANS occurred in 0.8%.

For the combination indication, epcoritamab is dosed for up to twelve 28-day cycles, with lenalidomide on days 1-21 of each cycle and rituximab for five cycles. To reduce the CRS risk, epcoritamab dosing is stepped-up in cycle 1, followed by 48 mg weekly in cycle 2 and 3, then 48 mg every 4 weeks through cycle 12. 

According to drugs.com, 48 mg/0.8 mL subcutaneous solution costs $16,105.86.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.