Long-Term Outcomes in Patients With Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) and Complete Response (CR) at 2‚ÄâYears With Epcoritamab Monotherapy: Novel Analysis of 3-Year Results From the Pivotal EPCORE NHL-1 Trial
Introduction/Background/Significance: In LBCL, duration of CR (DOCR) correlates with long-term outcomes. Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, is approved for patients with different types of R/R LBCL after ≥2 prior lines of treatment (pLOT). In the LBCL expansion cohort of EPCORE® NHL-1 (phase 1/2; NCT03625037), epcoritamab monotherapy led to durable CRs at 3 years of follow-up, with a median DOCR of 36 months. We report long-term efficacy and safety from a post hoc subgroup analysis of patients remaining in CR 2 years after initiating epcoritamab (patients in CR at 2 years).
Materials and Methods/Case Presentation/Objective: Adults with R/R CD20+ LBCL and ≥2 pLOT received subcutaneous epcoritamab (0.16- and 0.8-mg step-up doses in cycle [C] 1; 48-mg full doses thereafter) in 28-day Cs (C1–3, QW; C4–9, Q2W; C≥10, Q4W) until progressive disease (PD) or unacceptable toxicity. The primary endpoint was overall response rate (ORR).
Results/Description/Main Outcome Measures: As of May 3, 2024, ORR was 59% (92/157). Sixty-five patients (41%) had CR, 32 of whom remained in CR at 2 years. Among these 32 patients, median follow-up was 37 months (range, 32−46), median age was 63 years, 53% were female, and 66% had disease refractory to ≥2 consecutive pLOT. Patients in CR at 2 years had lower tumor burden at baseline (bulky disease >7 cm, 19% vs 34%; LDH, 294 vs 501 U/L) and lower baseline ferritin levels (383 vs 856 μg/L) than patients who were not in CR at 2 years; prior CAR T exposure was similar (38% vs 39%). Among the 32 patients in CR at 2 years, 31 had CR or partial response by the second response assessment at week 12. Median DOCR, progression-free survival, and overall survival were not reached, and an estimated 96% of patients remained in CR at 3 years. At data cutoff, the longest ongoing CR was >43 months. The safety profile of epcoritamab in patients in CR at 2 years was consistent with that in the overall EPCORE NHL-1 LBCL population. Median treatment duration for patients in CR at 2 years was 35 months (range, 8–43). Among 26 patients (81%) with ongoing treatment at 2 years, 19% (5/26) had ≥1 serious infection after 2 years; the most common was pneumonia (n=4). Two fatal infections occurred after the 2-year mark (COVID-19 pneumonia and pneumonia). Nineteen of the 32 patients in CR at 2 years (59%) remained on treatment at the data cutoff. One patient discontinued treatment due to PD and 12 discontinued for other reasons (including AEs; n=6). In the 12 patients who discontinued for reasons other than PD, CR was maintained after treatment discontinuation for a median of 14 months (range, 2−28).
Conclusions: Long-term disease remission was observed in patients with R/R LBCL who had ongoing CR 2‚Äâyears after starting epcoritamab. Safety remained manageable. These results highlight the benefits of epcoritamab for patients with R/R LBCL with ‚â•2 pLOT.
Encore statement: Results were previously presented in part at the American Society of Clinical Oncology Annual Meeting; May 30–June 3, 2025; Chicago, IL, USA.
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