Epcoritamab with rituximab plus lenalidomide provides durable responses in patients with high-risk follicular lymphoma, regardless of POD24 status
To date, there is no standard treatment approach for patients with high-risk, relapsed or refractory follicular lymphoma (R/R FL), including those with a disease that is primary refractory, double refractory, or refractory to prior anti-CD20 treatment and those who progress within 24 months after first-line chemoimmunotherapy (POD24). Epcoritamab plus rituximab and lenalidomide now showed potent antitumour activity and a manageable safety profile in a large R/R FL population. Furthermore, encouraging responses were seen in patients with high-risk disease, including those with POD24.
Follicular lymphoma (FL) is the second most common lymphoma, with a subset of patients exhibiting high-risk features associated with worse outcomes. Poor outcomes are especially seen in those who progress within 24 months after first-line chemoimmunotherapy (POD24) and those who are double refractory to both an anti-CD20 monoclonal antibody and an alkylating agent. Despite therapeutic advances, outcomes in relapsed/refractory follicular lymphoma (R/R FL) are suboptimal and there is no established standard of care for POD24 patients. Epcoritamab is a subcutaneously administered bispecific antibody that has demonstrated deep and durable responses with a manageable safety profile in the EPCORE NHL-1 trial. The immunomodulatory properties of lenalidomide may increase the therapeutic potential of epcoritamab. At EHA 2023, Dr. Sureda presented a pooled analyses from cohorts 2a and 2b of the ongoing phase 1/2 EPCORE™ NHL-2 trial (NCT04663347) of epcoritamab plus rituximab and lenalidomide (R2) in R/R FL.
Study design
Patients with R/R CD20-positive FL received subcutaneous epcoritamab + R2 for 12 cycles (28 days each). Epcoritamab was dosed QW in cycles 1–3, Q2W in cycles 4–9, and Q4W in cycles ≥10 (2a) or QW in cycles 1–2 and Q4W in cycles ≥3 (2b) for ≤2 year. Informed consent was obtained.
Results
Among the 111 patients included in the analysis, median age was 65 years, 60% of patients had Ann Arbor stage IV disease and 58% of patients had FLIPI 3-5. Median time from diagnosis to first dose of 63 months and median time from end of last line of therapy to first dose was 17 months. The median number of prior lines of therapy was one (range 1-7). At data cut-off, 73% of patients continued to receive treatment. Grade ≥ 3 treatment-emergent adverse events (TEAEs) were reported in 76% of patients. Two patients experienced ICANS, with a median time to resolution of 5.5 days. Furthermore, 48% of patients experienced CRS, although mostly of low grade (Grade 1, 34%; Grade 2, 12%; Grade 3, 2%). All events resolved, with a median time to resolution of 3 days. The most common TEAEs were neutropenia, CRS, injection site reactions and fatigue. Four fatal TEAEs occurred, all related to COVID-19.
After a median follow-up of 11.4 months, the overall response rates (ORR) was 98%, with a complete molecular response (CMR) rate of 87%. High overall response and CMR were obtained regardless of subgroups. Notably, patients achieved higher ORR/CMR rates with epcoritamab + R2 vs. their immediate prior therapy (ORR, 98% vs. 85%; CMR, 87% vs. 58%). For patients with POD24, ORR and CMR rate were 98% and 75.0%, respectively. High response rates were found to be independent of line of therapy. Median time to response was 1.4 months. Epcoritamab plus R2 led to durable complete response, including in POD24 patients (12-month estimate of complete response of 90%). The 12-month PFS was 78% in the overall populations and was reported at 77% for the POD24 population. Finally, epcoritamab plus R2 led to durable complete responses in other high-risk and non-high risk populations.
Conclusion
The addition of subcutaneous epcoritamab to R2 drives deep and durable remissions in R/R FL patients, including POD24 and other high-risk populations. Consistent with previous reports, epcoritamab has a manageable safety profile with no new safety signals. Combination regimens with subcutaneous epcoritamab are being studied in the ongoing, randomised, phase III EPCORE FL-1 trial as well as in a POD24 cohort in the EPCORE NHL-2 trial.
Reference
Sureda A, et al. Epcoritamab with rituximab + lenalidomide provides durable responses in patients with high-risk follicular lymphoma, regardless of POD24 status. Presented at EHA 2023; Abstract S222.
