Epcoritamab + GemOx achieves durable >2-year remissions in relapsed/refractory (R/R) 2L+ diffuse large B-cell lymphoma (DLBCL): Long-term data reinforce clinical potential of the regimen across a diverse patient population
Year: 2025
Type: conference-abstract
Abstract: Introduction Patients (pts) with R/R DLBCL ineligible for chimeric antigen receptor T cell (CAR T) therapy or autologous stem cell transplant (ASCT) have limited treatment (tx) options and poor outcomes. In R/R DLBCL, standard salvage therapy with gemcitabine plus oxaliplatin (GemOx) yielded a complete response (CR) rate of 25%, overall response rate (ORR) of 41%, median progression-free survival (mPFS) of 3.6 mo, and median overall survival (mOS) of 12.9 mo (Abramson JS, et al. Lancet 2024;404:1940–1954). In the EPCORE® NHL-2 trial (NCT04663347), epcoritamab (epcor), a CD3×CD20 bispecific antibody, combined with GemOx led to high response rates in pts with R/R DLBCL ineligible for ASCT. Here, we report long-term durability data from this cohort after >2 y of follow-up. Methods : Pts with CD20+ R/R LBCL ineligible for ASCT due to advanced age, performance status, or lack of response to prior ASCT received subcutaneous epcor (step-up doses: 0.16 mg, 0.8 mg; 48 mg thereafter) QW in cycles (C) 1–3, Q2W in C4–9, and Q4W in ≥C10. GemOx (gemcitabine 1000 mg/m², oxaliplatin 100 mg/m²) was given Q2W for 4 C (8 total doses). The primary endpoint was ORR by Lugano criteria. Minimal residual disease (MRD) negativity was assessed as a secondary endpoint, using the exploratory AVENIO Oncology circulating tumor DNA (ctDNA) method (cutoff: <1 mutant molecule per mL). Data cutoff was April 9, 2025; efficacy assessments were per investigator. Results : In total, 103 pts were treated. Median age was 72 y (range, 20–87). The pt population was 76% White, 4% Black/African American, and 4% Asian; pts were enrolled across the United States (US; 27%), Europe (72%), and Australia (1%). Pts had a median of 2 prior lines of tx (pLOT; range, 1–6); 37% had 1 pLOT; 61% had Ann Arbor stage IV, 7/66 (11%) assessed pts had double-hit/triple-hit disease, 33% had bulky disease (≥7 cm), 52% had primary refractory disease, 70% were refractory to last therapy, 10% had prior ASCT, and 28% had prior CAR T therapy. ORR was 81%, and 60% of pts had a CR. After a median follow-up of 27.9 mo (range, 1.0+ to 47.9), epcor + GemOx led to mPFS of 16.3 mo (95% CI, 8.3–not reached [NR]), and mOS of 28.2 mo (95% CI, 11.7–NR). At 2 y, an estimated 48% of all pts were progression-free and 53% were alive. Responses were durable, with a median duration of response of 27.3 mo (95% CI, 11.7–NR), and a median duration of complete response (mDOCR) of 40.7 mo (95% CI, 40.7–NR). An estimated 67% of complete responders remained in CR at 2 y. Among pts with 1 pLOT, CR rate was 74% and mDOCR was NR. Pts with >1 pLOT (some received up to 6 pLOTs) experienced clinically meaningful responses (CR rate: 52%), with mDOCR of 40.7 mo (95% CI, 17.5–NR). When analyzed by region, outcomes were consistent in pts from the US and Europe. Overall MRD negativity by C7 day 1 (D1), was observed in 71% (44/62) of MRD-evaluable pts. Deep and sustained MRD negativity through C7D1 was observed across difficult-to-treat subgroups. At data cutoff, 24% (25/103) of pts remained on tx. There were 16 pts who discontinued tx while in CR for reasons other than progressive disease or death; 12 (75%) of these pts remained in CR (median time since end of tx, 8.8 mo [range, 0.5–26.8]) at data cutoff. Safety was consistent with previous reports (Brody JD, et al. Blood 2025;145:1621–1631). Incidence of serious infections was highest (23%) in the first 24 weeks of tx, as expected, given known toxicities of the individual components, then decreased and remained consistent over time. With 14.7 mo more follow-up since the last report, 4 additional pts had an infection, and 4 additional pts experienced grade 5 treatment-emergent adverse events (pancreatic adenocarcinoma, lung infection, subacute sclerosing panencephalitis, COVID-19). Conclusions Epcor + GemOx demonstrated sustained remissions of >2 y, prolonged PFS and OS, and deep MRD negativity in challenging-to-treat 2L+ R/R DLBCL; these results are widely applicable to a diverse pt population across the US and Europe. With longer follow-up, the safety profile remained consistent with previous reports. These findings support the combinability of epcor with standard-of-care chemotherapy and offer an effective option for ASCT-ineligible pts, a population with otherwise limited tx choices.
Source: Blood
Institutions: Icahn School of Medicine at Mount Sinai, Charles University, Hospital Universitario Fundación Jiménez Díaz, Assistance Publique Hôpitaux de Marseille, General University Hospital in Prague, University of California, Los Angeles, Ronald Reagan UCLA Medical Center, Los Angeles Medical Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Candiolo Cancer Institute, National Health Service, Derriford Hospital, University Hospitals Plymouth NHS Trust, Odense University Hospital, University Medical Center Groningen, University of Groningen, AbbVie (United States), Genmab (United States), Genmab (Denmark), Aarhus University Hospital
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417012278
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