BACKGROUND: Studies in patients with rheumatoid arthritis and advanced follicular lymphoma have shown that CT-P10, a rituximab biosimilar, has equivalent or non-inferior efficacy and pharmacokinetics to rituximab. We aimed to assess the therapeutic equivalence of single-agent CT-P10 and rituximab in patients with newly diagnosed low-tumour burden follicular lymphoma. METHODS: In this ongoing, randomised, double-blind, parallel-group, active-controlled, phase 3 trial, adult patients (≥18 years) with stage II-IV low-tumour-burden follicular lymphoma were randomly assigned (1:1) using an interactive web or voice response system stratified by region, stage, and age to CT-P10 or US-sourced rituximab. Patients received CT-P10 or rituximab (375 mg/m2 intravenous) on day 1 of four 7-day cycles (induction period). Patients who had disease control after the induction period continued to a maintenance period of CT-P10 or rituximab administered every 8 weeks for six cycles and, if completed, a second year of maintenance therapy of additional CT-P10 (every 8 weeks for six cycles) was offered. The study was partially unmasked after database lock (Feb 23, 2018) for all data up to 7 months (before cycle 3 of the maintenance period). The primary endpoint was the proportion of patients who achieved an overall response by 7 months in the intention-to-treat population. Efficacy equivalence was shown if the two-sided 90% CIs for the treatment difference in the proportion of responders between CT-P10 and rituximab was within the equivalence margin of 17%. This trial is registered with ClinicalTrials.gov, number NCT02260804. FINDINGS: Between Nov 9, 2015, and Jan 4, 2018, 402 patients were assessed for eligibility, of whom 258 were randomly assigned: 130 to CT-P10 and 128 to rituximab. 108 (83%) of 130 patients assigned to CT-P10 and 104 (81%) of 128 assigned to rituximab achieved an overall response by month 7 (treatment difference estimate 1·8%; 90% CI -6·43 to 10·20). Therapeutic equivalence was shown (90% CIs were within the prespecified margin of 17%). The most common grade 3 or 4 treatment-emergent adverse events were decreased neutrophil count (two grade 3 in the CT-P10 group) and neutropenia (one in each group); all other grade 3 or 4 treatment-emergent adverse events occurred in one patient each. Six (5%) of 130 patients who received CT-P10 and three (2%) of 128 who received rituximab experienced at least one treatment-emergent serious adverse event. INTERPRETATION: CT-P10 was equivalent to rituximab in terms of efficacy and was well tolerated. CT-P10 monotherapy is suggested as a new therapeutic option for patients with low-tumour-burden follicular lymphoma. FUNDING: Celltrion, Inc.

Celltrion Inc Incheon South Korea

Comprehensive Cancer Center Ulm University Hospital of Ulm Ulm Germany

Department of Haematology and Oncology Kasugai Municipal Hospital Kasugai Japan; School of Medicine Fujita Medical University Toyoake Japan

Department of Haematology Jagiellonian University Kraków Poland

Department of Hematology Catholic Blood and Marrow Transplantation Center Seoul St Mary's Hospital The Catholic University of Korea Seoul South Korea

Department of Hematology Hospices Civils de Lyon Lyon France

Department of Hematology Hospital Arnau de Vilanova Valencia Spain

Department of Hematology Nizhniy Novgorod Region Clinical Hospital Nizhniy Novgorod Russia

Department of Hematology Shinshu University School of Medicine Matsumoto Japan

Department of Internal Medicine Universidad de la Frontera Temuco Chile

Department of Internal Medicine Yonsei University College of Medicine Severance Hospital Seoul South Korea

Department of Medicine Charles University General Hospital Prague Prague Czech Republic

Department of Onco Hematology Portuguese Institute of Oncology Porto Portugal

Division of Hematology and Bone Marrow Transplantation N N Blokhin Russian Cancer Research Center Moscow Russia

Division of Hematology and Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea

Hematology Department The Catalan Institute of Oncology The Josep Carreras Leukaemia Research Institute Hospital Germans Trias i Pujol Badalona Spain

N N Alexandrov Republican Scientific and Practical Centre of Oncology and Medical Radiology Minsk Belarus

Northern Institute for Cancer Care Newcastle University Newcastle upon Tyne UK

Russian Research Center for Radiology and Surgical Technologies Ministry of Health of the Russian Federation St Petersburg Russia

Shimane University Hospital Innovative Cancer Center Oncology Hematology Izumo Japan

Toni Stephenson Lymphoma Center and Department of Hematology and Hematopoietic Cell Transplantation City of Hope Duarte CA USA

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ClinicalTrials.gov
NCT02260804