Background: Epcoritamab, a CD3×CD20 bispecific antibody, is approved for adults with relapsed/refractory large B-cell lymphoma (R/R LBCL) for treatment to progression (TTP) or unacceptable toxicity after ≥2 lines of systemic therapy. With a 3-year median follow-up, in the pivotal Phase 2 EPCORE® NHL-1 study (NCT03625037), epcoritamab monotherapy resulted in sustained deep and durable responses with patients in complete response (CR) achieving a median duration of complete response (DOCR) of 36.1 months (95% CI, 20.2-not reached [NR]); the median overall survival (OS) was NR. The safety profile was manageable (Vose JM, et al.Blood. 2024;[Supplement 1]:4480). The aim of this analysis was to evaluate the durability of response of patients with R/R LBCL in CR who either paused or discontinued epcoritamab treatment.

Methods: Adults with R/R CD20+ LBCL (including diffuse LBCL [DLBCL], high-grade B-cell lymphoma [HGBCL], primary mediastinal [PM] BCL, and follicular lymphoma [FL] grade 3B) and ≥2 prior lines of systemic therapy were enrolled in the expansion phase of the study and treated with subcutaneous epcoritamab (0.16 mg and 0.8 mg step-up doses followed by 48-mg full doses) in 28-day cycles according to the approved dosing schedule: once weekly, cycles 1-3; every 2 weeks, cycles 4-9; every 4 weeks cycles ≥10 until progressive disease or unacceptable toxicity. Corticosteroid prophylaxis was given during cycle 1. The primary endpoint was overall response rate (ORR) per Lugano criteria. Efficacy results were based on investigator's assessment (Vose JM, et al. Blood. 2024;[Supplement 1]:4480). Patients in CR who had treatment pauses/dose delays epcoritamab for >6 weeks after initial treatment prior to restarting treatment and patients in CR who permanently discontinued epcoritamab for reasons other than progressive disease or death in the EPCORE® NHL-1 trial were included in this analysis.

Results: At the data cutoff date of May 3, 2024, 16 patients (n=15, DLBCL; n=1, other [PMBCL]) had treatment pauses/dose delays and 32 patients (n=27, DLBCL; n=5, other [n=2, HGBCL; n=2, PMBCL; n=1, FL Grade 3B]) had discontinued treatment while in CR.

For patients in CR whohad treatmentpauses/delays of epcoritamab for >6 weeks, the median follow-up time was 37.0 months (95% CI, 35.0-41.1), the median duration of treatment hold was 70.5 days (range, 48–257), with a median duration of treatment prior to pause of 18.9 months (range, 9.3–31.7). Themedian age was 69 years (range, 20–83), and all 16 patients had an ECOG PS 0–1. The most common reason for treatment pauses/delays was adverse events (AEs) including COVID-19. Both the median duration of response (DOR) and median DOCR were NR (95% CI, 32.0–NR). The median progression-free survival (PFS) was NR (95% CI, 34.2–NR), and the median OS was NR (95% CI, NR–NR). Of these 16 patients, 15 had a post-pause lymphoma assessment scan and all 15 maintained their CR following treatment reinitiation.

For patients in CR who discontinued epcoritamab, the median follow-up time was 37.1 months (95% CI, 35.0-39.9), the median duration of treatment prior to discontinuation was 13.2 months (range, 2.6–35.7). Median age was 63 years (range, 20–82), and all 32 patients had an ECOG PS 0–1. The most common reason for treatment discontinuation was AEs followed by transplant, patient/investigator decision, maximum clinical benefit, or other reasons. The median DOR was 29.7 months (95% CI, 18.8–NR), and the median DOCR was 26.5 months (95% CI, 15.8–NR). The median PFS was 30.9 months (95% CI, 20.5–NR), and the median OS was NR (27.7–NR).

Conclusions: These findings demonstrate that patients with relapsed/refractory LBCL in CR may sustain durable remissions even after temporary treatment pauses or discontinuation for reasons other than progression. While these outcomes highlight the potential flexibility of the epcoritamab regimen, treatment until progression remains the optimal approach as reflected in the main EPCORE® NHL-1 results. With a median DOCR exceeding 3 years and the longest reported median DOCR for a bispecific antibody in this setting, epcoritamab continues to show a favorable balance of efficacy and manageability in 3L+ LBCL.

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2025
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