Comparison of epcoritamab, lenalidomide, and rituximab versus usual care in relapsed/refractory follicular lymphoma

Patients with relapsed/refractory follicular lymphoma (R/R FL) often experience multiple disease recurrences with progressively shorter duration of remission. Chemoimmunotherapy (CIT) is commonly used for R/R FL in second-line and later settings but is not curative; novel, improved treatments are needed. Epcoritamab, a CD3 × CD20 bispecific antibody, is approved as monotherapy for R/R FL after ≥ 2 lines of therapy (LOTs) and combined with lenalidomide and rituximab (R²) for R/R FL. Epcoritamab + R² pivotal data demonstrated superiority over R², but no comparison of epcoritamab + R² versus CIT exists. Therefore, we conducted an adjusted comparative analysis of epcoritamab + R² from arm 2 of the phase 1b/2 EPCORE NHL-2 trial (NCT04663347; n = 111; US, 23.4%) versus R²/CIT using COTA individual patient-level electronic health records (n = 380; US, 100%) of patients with R/R FL after ≥ 1 previous LOT. Epcoritamab + R² improved response rates over R²/CIT (overall response, 96.9% versus 80.5%, P < .001; complete response, 90.2% versus 55.1%, P < .001). Epcoritamab + R² improved duration of response (HR, 0.29 [95% CI, 0.18-0.47]; P < .001), duration of complete response (HR, 0.31 [95% CI, 0.17-0.55]; P < .001), progression-free survival (HR, 0.43 [95% CI, 0.28-0.68]; P < .001), and overall survival (HR, 0.33 [95% CI, 0.16-0.70]; P = .003) over R²/CIT. These findings support epcoritamab + R² as a promising chemotherapy-free treatment option for R/R FL.