Fixed-Duration Epcoritamab Monotherapy or Epcoritamab Plus Lenalidomide Leads to High Overall Response Rates in Elderly Patients With Comorbidities and Newly Diagnosed Large B-Cell Lymphoma (LBCL): Results From the Phase 2 EPCORE DLBCL-3 Trial
Introduction/Background/Significance: R-mini-CHOP is commonly used for treatment of elderly, frail patients with newly diagnosed LBCL. However, many patients are not suitable candidates for standard chemotherapy-based regimens due to advanced age and/or comorbidities. Epcoritamab, a CD3xCD20 bispecific antibody, is approved as monotherapy for different types of relapsed or refractory LBCL after ≥2 lines of systemic therapy. EPCORE® DLBCL-3 (NCT05660967) is a 2-stage, randomized phase 2 trial evaluating epcoritamab monotherapy vs epcoritamab+lenalidomide in elderly patients with newly diagnosed LBCL and comorbidities. We report EPCORE DLBCL-3 stage 1 results, including from the epcoritamab+lenalidomide arm.
Materials and Methods/Case Presentation/Objective: In stage 1, elderly patients with newly diagnosed CD20+ LBCL who were ineligible for anthracyclines due to age ≥80 years or age ≥75 years with underlying comorbidities were randomly assigned to receive epcoritamab or epcoritamab+lenalidomide as first-line treatment for up to 12 cycles (28 days/cycle). Patients received step-up doses of subcutaneous epcoritamab (C1D1, 0.16 mg; C1D8, 0.8 mg) followed by 48-mg full doses (QW C1–3, Q4W C4–12). Patients in the epcoritamab+lenalidomide arm received oral lenalidomide ≤20 mg daily on D1–21 of each cycle. Primary endpoint was complete response (CR) rate (Lugano criteria).
Results/Description/Main Outcome Measures: As of September 21, 2024, 88 patients were randomly assigned to receive epcoritamab monotherapy (n=45) or epcoritamab+lenalidomide (n=43); median follow-up was 9.5 and 9.2 months, respectively. Baseline demographic and disease characteristics were generally balanced across arms. At data cutoff, 20% of treated patients in the epcoritamab arm (n=44) and 10% of treated patients in the epcoritamab+lenalidomide arm (n=42) had completed treatment per protocol; 32% and 31%, respectively, were ongoing treatment; and 48% and 60% discontinued. Among response-evaluable patients (epcoritamab, n=40; epcoritamab+lenalidomide, n=37), overall response/CR rates were 78%/70% and 70%/49%, respectively. Median duration of CR was not reached in either arm. At 6 months, an estimated 84% (epcoritamab) and 85% (epcoritamab+lenalidomide) of complete responders remained in CR; an estimated 73% and 56% of patients, respectively, remained progression free. The most common treatment-emergent AEs (TEAEs) with epcoritamab were CRS (70%), constipation (23%), and fatigue (23%). The most common TEAEs with epcoritamab+lenalidomide were CRS (71%), neutropenia (45%), and anemia (43%). TEAEs led to treatment discontinuation in 18% (epcoritamab) and 33% (epcoritamab+lenalidomide) of treated patients; 1 fatal treatment-related AE occurred in each arm. CRS was primarily low grade and timing was predictable; most events occurred in C1. CRS resolved in 97%/100% of patients with CRS in the epcoritamab/epcoritamab+lenalidomide arms. ICANS occurred in 7 patients in each arm (all grade ≤3); 1 patient in each arm discontinued epcoritamab due to ICANS.
Conclusions: Fixed-duration epcoritamab with or without lenalidomide demonstrated high overall response rates in elderly patients with newly diagnosed LBCL and comorbidities. Safety was as expected and consistent with previous reports. Based on promising efficacy and manageable safety as a chemotherapy-free regimen for this population with high unmet need, epcoritamab monotherapy was selected for further enrollment in stage 2 of the study.
Encore statement: The monotherapy results were previously presented at the American Society of Hematology Annual Meeting; December 7–10, 2024; San Diego, CA, USA.
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