Fixed-duration epcoritamab plus R2 drives favorable outcomes in relapsed or refractory follicular lymphoma

Author(s): Falchi, Lorenzo1; Sureda, Anna2; Leppä, Sirpa3; Vermaat, Joost S. P.4; Nijland, Marcel5; Christensen, Jacob Haaber6; de Vos, Sven7; Holte, Harald8; Merryman, Reid W.9; Lugtenburg, Pieternella J.10; Abrisqueta, Pau11; Linton, Kim M.12; Sunkersett, Gauri13; Hoehn, Daniela14; Rana, Ali14; Abbas, Aqeel14; Marek, Jennifer14; Hao, Yi14; Steele, Andrew J.14; Morehouse, Christopher14; Hutchings, Martin15; Belada, David16;
Source: Blood (2025) 146 (22): 2629–2640.
Original Article
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The EPCORE NHL-2 phase 1b/2 trial evaluated fixed-duration epcoritamab plus R2 in R/R FL after at least one prior line, showing impressive efficacy with an overall response rate (ORR) of 96% and a complete response (CR) of 88%, and 2-year rates for remaining in CR (82%), progression-free survival (PFS) (76%), overall survival (OS) (90%), and freedom from next therapy (84%)—all with non-reached medians. High-risk groups did just as well, with CR rates of 90% in primary refractory, 82% in double refractory. MRD negativity was achieved by 86% overall. Safety was manageable, with mostly low-grade CRS (grade 1/2/3: 38%/11%/2%), neutropenia (65%), and COVID-19 (59%)—notably, no CRS-related discontinuations. This chemo-free, off-the-shelf regimen is delivering deep, durable remissions with practical outpatient dosing—something we’ve all been hoping to see for R/R FL.

ABSTRACT

Epcoritamab is a subcutaneous CD3×CD20 bispecific antibody approved as monotherapy for relapsed/refractory (R/R) follicular lymphoma (FL). We evaluated fixed-duration epcoritamab with rituximab plus lenalidomide (R2) in R/R FL in arm 2 of EPCORE NHL-2 (phase 1b/2). Patients received epcoritamab (2 step-up doses, then 48-mg full doses) for up to 2 years, and R2 for up to 12 cycles (28 days per cycle). The primary end point was overall response rate (ORR) per investigator assessment (Lugano criteria). As of 21 September 2024, 108 patients received ≥1 epcoritamab dose in expansion (median follow-up, 28.2 months). Median age was 65 years; 57% had 1 previous line of therapy. ORR and complete response (CR) rate were 96% and 88%, respectively; CR rates in patients with high-risk features were 90% (primary refractory), 82% (refractory to anti-CD20 and an alkylating agent), and 83% (disease progression within 24 months of first-line therapy). Two-year estimates for remaining in CR, progression-free survival, overall survival, and not starting next antilymphoma therapy were 82%, 76%, 90%, and 84%, respectively. Minimal residual disease negativity was observed in 86% of evaluable patients (clonoSEQ assay). Common treatment-emergent adverse events (TEAEs) included neutropenia (65%), COVID-19 (59%), and cytokine release syndrome (CRS; 51%). Grade ≥3 TEAEs occurred in 87% of patients; 5 had grade 5 TEAEs (all COVID-19). CRS events were mostly low grade (grade 1, 38%; grade 2, 11%; grade 3, 2%), all resolved, and none led to epcoritamab discontinuation. Fixed-duration epcoritamab plus R2 demonstrated deep, durable responses with manageable safety and favorable outcomes in R/R FL, irrespective of risk features. This trial was registered at www.ClinicalTrials.gov as #NCT04663347.

Author Affiliations

1Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; 2Clinical Hematology Department, Institut Català d’Oncologia, L’Hospitalet, IDIBELL, Universitat de Barcelona, Barcelona, Spain; 3Department of Oncology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland; 4Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands; 5Department of Hematology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands; 6Department of Haematology, Odense University Hospital, Odense, Denmark; 7Department of Medicine, Hematology/Oncology, Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, CA; 8Department of Oncology, Oslo University Hospital and KG Jebsen Center for B-cell Malignancies, Oslo, Norway; 9Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; 10Department of Hematology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands; 11Department of Hematology, Hospital Universitario Vall d’Hebron, Barcelona, Spain; 12Division of Cancer Sciences, The Christie NHS Foundation Trust, Manchester Cancer Research Centre, University of Manchester, Manchester, United Kingdom; 13AbbVie, North Chicago, IL; 14Genmab, Plainsboro, NJ; 15Department of Haematology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark; 164th Department of Internal Medicine, Haematology, Hospital and Faculty of Medicine, Charles University, Hradec Králové, Czech Republic

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