Epcoritamab Plus R2 Maintains Quality of Life in R/R Follicular
Key Clinical Summary
- In the phase 3 EPCORE FL-1 study, epcoritamab plus rituximab and lenalidomide (E+R2) achieved a 75% complete response rate vs 43% with R2 alone in relapsed or refractory follicular lymphoma (R/R FL).
- Despite higher rates of grade 3/4 adverse events (88% vs 62%), health-related quality of life (HRQoL) was maintained and comparable between treatment arms.
- Patient-reported outcomes showed no clinically meaningful decline, supporting E+R2 as a chemotherapy-free regimen with preserved quality of life.
R/R FL remains a chronic, relapsing disease with limited chemotherapy-free treatment options. New findings from the phase 3 EPCORE FL-1 trial suggest that adding epcoritamab to rituximab and lenalidomide (E+R2) may improve clinical outcomes without compromising patient quality of life, a key consideration in this indolent but burdensome disease.
Study Findings
The EPCORE FL-1 trial evaluated fixed-duration E+R2 vs standard rituximab plus lenalidomide (R2) in patients with R/R FL. A total of 488 patients were randomized 1:1, with 243 receiving E+R2 and 245 receiving R2 alone.
Efficacy outcomes favored the combination regimen. Complete response rates were 75% in the E+R2 arm compared with 43% in the R2 arm, highlighting a substantial improvement in disease control.
HRQoL was assessed using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) instrument. At baseline, both groups had high scores, reflecting relatively low symptom burden. Across treatment cycles, patients receiving E+R2 experienced a modest early decline in quality-of-life measures during cycles 2 to 4. However, scores returned to baseline by cycle 5 and remained comparable to R2 through the remainder of treatment.
Importantly, changes in total score, treatment outcome index, and lymphoma-specific symptom scores did not meet thresholds for clinically meaningful deterioration at any time point. Patient-reported symptoms—including fatigue, pain, fever, and weight loss—remained stable across both treatment arms.
Although grade 3/4 adverse events were more frequent with E+R2 (88% vs 62%), these did not translate into sustained declines in patient-reported quality of life.
Clinical Implications
For managed care decision-makers, these findings highlight a key trade-off in oncology treatment selection: improved efficacy often comes with increased toxicity. However, the EPCORE FL-1 data suggest that higher-grade adverse events with E+R2 do not necessarily translate into worse patient experience or reduced functional status.
Maintaining HRQoL is particularly important in R/R FL, where patients may receive multiple lines of therapy over time. A chemotherapy-free regimen that improves response rates while preserving quality of life may offer both clinical and economic value by reducing downstream disease burden and treatment switching.
The fixed-duration design of E+R2 also has implications for cost predictability and resource utilization, potentially offering advantages over indefinite therapy strategies.
Conclusion
E+R2 demonstrated improved efficacy without compromising quality of life in patients with R/R FL. These findings support its potential role as a next-generation, chemotherapy-free standard of care in this setting.
Reference
Linton K, Morschhauser F, Nijland M, et al. Health-related quality of life (HRQoL) in patients with relapsed/refractory follicular lymphoma treated with epcoritamab in combination with rituximab plus lenalidomide (E+R2): Primary results of the EPCORE FL-1 trial. Blood. 2025;146(1):5370. doi:10.1182/blood-2025-5370
