Epcoritamab + R-mini-CHOP results in 2-year remissions and high MRD negativity rates in elderly patients with newly diagnosed DLBCL: Results from the EPCORE NHL-2 trial
Year: 2025
Type: conference-abstract
Abstract: Introduction: Dose-attenuated rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-mini-CHOP) is a standard of care (SOC) for patients with newly diagnosed (1L) diffuse large B-cell lymphoma (DLBCL) unable to receive full-dose R-CHOP due to age or comorbidities. However, outcomes following R-mini-CHOP remain suboptimal, with overall response rates (ORR) of 60%–80%, complete response (CR) rates of 40%–60%, 2-year PFS of 51%, and 2-year OS of 60% (Al-Sarayfi D, et al. Am J Hematol 2024;99:216–222). In the EPCORE® NHL-2 trial (phase 1b/2; NCT04663347), epcoritamab, a CD3×CD20 bispecific antibody, combined with R-mini-CHOP demonstrated promising efficacy and manageable safety in elderly patients with 1L DLBCL ineligible for full-dose R-CHOP (Leslie LA, et al. Blood 2024;144[Suppl 1]:3106). Here, we present results from this cohort after 2 years of follow-up. Methods: Adults with newly diagnosed CD20+ DLBCL who were ineligible for full-dose R-CHOP due to age ≥75 years or age ≥65 years with comorbidities, received fixed-duration subcutaneous epcoritamab 48 mg (QW, cycle(s) [C] 1–2 [21 days each]; Q3W, C3–6 [21 d each]; Q4W, C7–8 [28 d each]; with step-up dosing in C1 [0.16 mg on C1 day 1 (D1) and 0.8 mg on C1D8]) + R-mini-CHOP (Q3W, C1–6). The primary endpoint was ORR per Lugano criteria. Minimal residual disease (MRD) negativity was assessed as a secondary endpoint using the exploratory AVENIO Oncology circulating tumor DNA (ctDNA) method; MRD negativity was defined as <1 mutant molecule per mL. Results: As of April 9, 2025, 28 patients had received epcoritamab + R-mini-CHOP. Median age was 81 years (range, 74–90), 89% of patients had de novo DLBCL, 46% had germinal center B-cell (GCB) and 39% had non-GCB, 68% had International Prognostic Index (IPI) scores 3–5, 64% had elevated LDH, and 39% had bulky disease (≥7 cm). Most patients (22/28; 79%) completed treatment as planned, and median relative dose intensity of R-mini-CHOP was ≥94%. With a median follow-up of 28.0 months (range, 2.8–34.5), the ORR was 89% and the CR rate was 86%. Median duration of response and duration of CR were not reached (NR) at data cutoff. At 2 years, an estimated 78% of all responses and 78% of CRs were maintained. Median PFS and median OS were NR. The estimated 2-year PFS and OS rates were 76% and 82%, respectively, at data cutoff. 20/22 patients who completed treatment had a CR at end of treatment; with a median follow-up for duration of CR of 22.6 months after treatment end, 18/20 (90%) remained in CR at data cutoff. MRD negativity was reported for 20 (95%) of the 21 patients evaluable for MRD at any time; 16/20 were MRD negative by C3D1. Among patients who were MRD negative at C3D1 and had paired longitudinal samples, 86% (12/14) sustained their MRD negativity through C6D1. High rates of MRD negativity were observed among high-risk subgroups, such as patients with bulky disease (8/9, 89%) and IPI score 3-5 (14/15, 93%). Safety was consistent with prior reports (Leslie LA, et al. Blood 2024;144 [Suppl 1]:3106). Eight (29%) patients experienced a grade ≥3 infection, with the majority (in 6/8 patients) occurring within the first 6 cycles of treatment. Treatment-emergent AEs led to epcoritamab discontinuation in 3 (11%) patients, including grade 2 rhinitis, grade 2 cytokine release syndrome, and grade 5 confusional state and cytomegalovirus infection reactivation in a patient aged 90 years also diagnosed with acute cerebrovascular accident. Conclusions: Fixed-duration epcoritamab + R-mini-CHOP led to high ORR and CR rates, rapid and sustained MRD negativity, and durable remissions in elderly patients with newly diagnosed DLBCL ineligible for full-dose R-CHOP. Despite the elderly population, outcomes compare favorably with historical outcomes of R-mini-CHOP alone. These results, along with those from other arms of the trial, support combinations of epcoritamab with SOC across a range of disease settings and patient populations.
Source: Blood
Authors: Chan Cheah, Juraj Ďuraš, David Belada, Justin Darrah, Yasmin Karimi, Franck Morschhauser, Gerardo Musuraca, Mats Hellstrom, Katerina Kopeckova, Lori Leslie, Anna Sureda Balarí, Catherine Thieblemont, Umberto Vitolo, Kojo Osei-Bonsu, Yi Hao, Monica Wielgos-Bonvallet, Mina Khoshdeli, Aidan Reilly, Malene Risum, Joost Vermaat, Joshua Brody
Institutions: The University of Western Australia, Sir Charles Gairdner Hospital, University Hospital Ostrava, Charles University, Cedars-Sinai Medical Center, University of Michigan, Université de Lille, Centre Hospitalier Universitaire de Lille, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Uppsala University, Uppsala University Hospital, General University Hospital in Prague, Hackensack Meridian Health, Hackensack Meridian School of Medicine, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis, Candiolo Cancer Institute, AbbVie (United States), Genmab (United States), Genmab (Denmark), Leiden University Medical Center, Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7108472836