Outpatient administration of epcoritamab monotherapy for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL): Results from EPCORE NHL-6 by race and ethnicity

Abstract

Abstract Background: DLBCL is most frequently diagnosed in White males and least commonly in Black females (Wang SS Semin Hematol. 2023;60:255-266). Limited data exists on the safety and efficacy of bispecific antibodies (bsAbs) in DLBCL by race and ethnicity. Epcoritamab, a CD3×CD20 bsAb, is approved for R/R DLBCL after ≥2 lines of treatment. Previous EPCORE NHL-6 data showed patients could be safely monitored in the outpatient setting at both academic and community sites across the US (Vaidya et al, ICML 2025 Abstract 625). Here, we report outcomes by racial/ethnic subgroups (Black/Hispanic vs White/Asian). Methods: EPCORE NHL-6 (NCT05451810) is an open-label phase 2 study.Eligible patients with R/R DLBCL were ≥18 years old, had ECOG PS 0–2, received ≥1 prior line of therapy including anti-CD20 antibody, and failed/were ineligible for autologous hematopoietic stem cell transplantation. Epcoritamab was administered in 28-day cycles (C). C1 included 2 step-up doses (0.16 mg, 0.8 mg), and full dose (48 mg) beginning at C1D15. The administration frequency was QW in C1–3, Q2W in C4–9, and Q4W in remaining cycles. Outpatient monitoring was implemented across academic and community centers. Patients were required to stay within ~30 min of the investigator's hospital for 24 hrs after the first full dose of epcoritamab. Premedication with antihistamines, antipyretics, and corticosteroids was mandated as cytokine release syndrome (CRS) prophylaxis. Primary endpoints were grade (G) 3+ CRS, immune cell-associated neurotoxicity syndrome (ICANS), and neurologic events. Secondary endpoints included responses assessed by investigators per Lugano criteria, and efficacy and safety outcomes. Results: Ninety-two US patients with R/R DLBCL (2L, n=42; 3L+, n=50) were enrolled at academic (n=51) and community (n=41) sites. The Black/Hispanic subgroup had 26 patients (Black or African American, n=14; Hispanic/Latino, n=20) and the White/Asian subgroup had 66 patients (not Hispanic/Latino White, n=62; Asian, n=3; race not reported, n=1). Baseline patient and disease characteristics were as follows (Black/Hispanic vs White/Asian): 42.3% vs 63.6% male, 65.0 vs 70.5 years median age, 57.7% vs 48.5% International Prognostic Index ≥3, 80.8% vs 83.3% Ann Arbor Staging stage III–IV, 23.1% vs 24.2% prior treatment with CAR T, 7.7% vs 15.2% bulky disease 7–10 cm, and 7.7% vs 12.1% bulky disease >10 cm. Among 88 patients who received the first full dose, 81 (92%) were monitored in the outpatient setting and 7 monitored inpatient (5 were admitted per investigator's discretion and 2 were already admitted). At the data cutoff, 50% of patients remained on treatment. CRS was reported in 38.5% (G1, 15.4%; G2, 23.1%) of patients in the Black/Hispanic and 40.9% (G1, 24.2%; G2, 13.6%; G3, 3.0%) in the White/Asian subgroup. Most CRS occurred after the first full dose of epcoritamab, and median time to onset after the first full dose was similar across the subgroups (Black/Hispanic, 20.6 hr [range, 7.7–165.1]; White/Asian, 31.8 hr [range, 8.7–226.4]). CRS was predictable in timing, all events resolved (median time to CRS resolution: Black/Hispanic, 2.0 days [range, 1–6]; White/Asian, 2.0 days [range, 1–24]), and none led to treatment discontinuation. ICANS occurred in 7.7% (all G1) of patients in the Black/Hispanic subgroup and 7.6% (G1, 3.0%; G2, 3.0%; G3, 1.5%) in the White/Asian. All events resolved with no treatment discontinuations. Overall response rates were 61.5% (complete response rate [CRR], 53.8%) in the Black/Hispanic and 62.1% (CRR, 37.9%) in the White/Asian subgroup, with respective median duration of response of not reached (NR) mo (95% CI, 2.9–NR) and 15.2 mo (95% CI, 4.4–NR). Median progression-free survival was NR (95% CI, 1.6 mo–NR) in the Black/Hispanic and 5.7 mo (95% CI, 2.9–16.4) in the White/Asian subgroup, with median duration of study follow-up of 6.0 mo (95% CI, 3.8–8.5) and 8.2 mo (95% CI, 6.0–10.4), respectively. Conclusions: Patients with 2L+ DLBCL receiving epcoritamab were monitored in the outpatient setting. CRS and ICANS incidence and severity were consistent across racial subgroups and with previous outpatient cohort data, as well as data from the pivotal EPCORE NHL-1 trial. These results provide new insights into the efficacy and safety of bsAbs in ethnically and racially diverse patients and further reinforce the feasibility of outpatient administration across patient types and practice settings.