P. Abrisqueta

Clinical trial Open access Sep 2026

Epcoritamab with rituximab and lenalidomide as first-line treatment for follicular lymphoma (EPCORE NHL-2): an open-label, multicentre, phase 1/2 b trial.

BACKGROUND Chemotherapy-free regimens, such as rituximab and lenalidomide, are attractive first-line treatment options for follicular lymphoma, but combinations providing deeper, more durable responses are needed. We aimed to assess 3-year activity and safety of epcoritamab, a subcutaneously administered CD3 × CD20 bispecific antibody, plus rituximab-lenalidomide as first-line treatment for follicular lymphoma. METHODS EPCORE NHL-2 is an open-label, phase 1b/2, clinical trial. Arm 6 of the study was conducted at 20 hospitals in six countries in Europe (Spain, the Netherlands, Czech Republic, Sweden, Belgium, and Denmark) and the USA in patients aged 18 years and older with CD20+, histologically confirmed grade 1-3A follicular lymphoma, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received intravenous rituximab 375 mg/m2 once per week in cycle 1 (28 days per cycle) and every 4 weeks in cycles 2-6; oral lenalidomide 20 mg daily on days 1-21 of cycles 1-12; and subcutaneous epcoritamab in a two-step-up dosing regimen of a 0·16 mg priming dose, followed by a 0·8 mg intermediate dose, then full 48 mg doses in cycle 1, 48 mg once per week in cycle 2, and 48 mg every 4 weeks in subsequent cycles for up to 2 years. The primary endpoint was investigator-assessed overall response rate by Lugano Response Criteria for Malignant Lymphoma. The full analysis set and the safety set included all patients who received one or more doses of trial drug. This study is registered with ClinicalTrials.gov (NCT04663347) and is ongoing (closed to new participants). FINDINGS Between Sept 23, 2021, and May 3, 2022, 45 patients were assessed for eligibility in Arm 6, 41 of whom were eligible and included in the full analysis and safety sets. 21 (51%) of 41 patients were male and 20 (49%) were female; 27 (66%) of patients were White, one (2%) was Asian, one (2%) was of another race, and 12 (29%) did not have race reported. At a median follow-up of 35·9 months (IQR 35·8-36·6) the overall response rate was 95% (95% CI 84-99; 39 of 41 patients). The most common grade 3-4 adverse events were neutropenia (20 [49%] of 41 patients), infections (12 [29%]), COVID-19 (six [15%]), and alanine aminotransferase increase (five [12%]). Serious adverse events occurred in 29 (71%) patients, including cytokine release syndrome (13 [32%]), serious infections (13 [32%]; one grade 2), pyrexia (three [7%]), organising pneumonia (one [2%]), pleural effusion (one [2%]), pneumonitis (one [2%]), pulmonary embolism (one [2%]), maculopapular rash (two [5%]), toxic skin eruption (one [2%]), atrial fibrillation (one [2%]), diarrhoea (one [2%]), dehydration (one [2%]), ovarian epithelial cancer (one [2%]), cerebrovascular accident (one [2%]), and thrombophlebitis (one [2%]). Treatment-related deaths occurred in three (7%) patients due to septic shock, progressive multifocal leukoencephalopathy, and COVID-19. INTERPRETATION Epcoritamab plus rituximab-lenalidomide showed high activity in first-line treatment for follicular lymphoma, with 95% of patients having a response over 3 years of follow-up, supporting this treatment regimen as a promising approach that warrants further analysis to ascertain its role in this setting. FUNDING Genmab and AbbVie.

L. Falchi, J. Vermaat, Joshua D. Brody et al. · The Lancet Haematology · 0 citations

Open access Aug 2026

Prolonged SARS-CoV-2 infection in hematologic malignancies: clinical impact, risk factors and intra-host viral evolution

Introduction Prolonged SARS-CoV-2 infection in hematologic patients may go unrecognized. The aim of the study is to describe the incidence, risk factors, viral evolution and clinical outcomes of prolonged SARS-CoV-2 infection in patients with hematologic malignancies. Methods This is a prospective, observational study. We performed a longitudinal follow-up rRT-PCR with cycle threshold (Ct) assessment until negativization to 500 patients diagnosed with hematologic malignancies who suffered SARS-CoV-2 infection between March 2020 and August 2023. We considered prolonged COVID-19 to a positive rRT-PCR with a Ct <35 beyond 30 days after microbiological diagnosis with the same viral variant. Results Prolonged SARS-CoV-2 infection is a complication in 44.8% (156/348) of patients diagnosed with hematologic malignancies with a median time of rRT-PCR positivity of 58 days (IQR 43-88). Active treatment with bispecific antibodies, anti-CD20 antibodies, BTK inhibitors and immunosuppressive drugs for GvHD are significantly associated with prolonged viral shedding; as well as lack of vaccination, lesser booster vaccine doses, absence of anti-S seroconversion after immunization, severe acute infection and delayed antiviral treatment. A 56.4% (88/156) of patients exhibit a pattern of remitting and relapsing symptoms and fluctuant viral load. During those exacerbations, 70.5% of patients experienced an increase in the severity of the acute infection and 34% developed pneumopathy, particularly organizing pneumonia. Persistent COVID-19 caused 54.5% (85/156) of patients to interrupt and 19.9% (31/156) to suspend indefinitely their hematologic treatments. Viral intra-host mutations across the entire viral genome, predominantly within the spike were detected in most patients with prolonged COVID-19, especially in those who received anti-SARS-CoV-2 mAb as sotrovimab (E340, R346, K356) and tixagevimab/cilgavimab (R346, K444 and G446). These substitutions are associated with reduced viral susceptibility. Discussion Prolonged SARS-CoV-2 infection in hematologic patients is frequent and leads to persistent viral replication, significant morbidity and the emergence of intra-host viral mutations. Optimizing treatments and monitoring viral clearance are medical needs for high-risk patients.

M. Jiménez, Cristina Andrés, Alejandra González-Sánchez et al. · Frontiers in Immunology · 0 citations