Efficacy and safety of rituximab biosimilar (DRL_RI) versus MabThera^® in low-tumor-burden follicular lymphoma: the FLINTER study.

IF 4.3 2区医学 Q2 ONCOLOGY

Therapeutic Advances in Medical Oncology Pub Date : 2025-05-24 eCollection Date: 2025-01-01 DOI:10.1177/17588359251339925

Narendra Maharaj, Dharma Rao Uppada, Anand Eswaraiah, Ranjith Kakkattu, Pramod Reddy, Volha A Kalenik, David Belada, Ana Oliveira Ramos, Jin Seok Kim, Yauheni V Baranau

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引用次数: 0

Abstract

Background and objectives: This phase III study (RI-01-006; FLINTER) was conducted to demonstrate equivalent efficacy of DRL_RI to EU-approved rituximab (MabThera^®) in patients with previously untreated Stage II-IV, CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL). This study also evaluated safety, immunogenicity, rituximab concentrations, and pharmacodynamics (PD) of DRL_RI compared with MabThera.

Design and methods: Previously untreated, stage II-IV, CD20-positive LTB-FL patients (N = 317) were randomized (1:1) to receive DRL_RI (n = 162) or MabThera (n = 155) as intravenous infusions of 375 mg/m² weekly for 4 weeks (induction period), and thereafter every 8 weeks from Week 12 to Week 36 (maintenance treatment), and followed up till Week 52. The primary end point was best overall response rate (BORR) up to Week 28 based on blinded independent central review. Efficacy equivalence was demonstrated if the two-sided 90% confidence interval (CI) for BORR difference was within the prespecified equivalence margin (±17%). Secondary end points included objective and complete responses, duration of response, progression-free survival, overall survival, safety, immunogenicity, mean serum concentrations, and PD.

Results: The BORR up to Week 28 was 80.2% versus 79.4% for DRL_RI versus MabThera group; with a difference of 0.89% (90% CI: -6.67 to 8.48; 95% CI: -8.05 to 9.93 within the prespecified margin). Both treatment groups were comparable for all secondary efficacy end points. Treatment-emergent adverse events were reported in 68.6% of patients; safety, immunogenicity, and mean serum concentrations were similar between groups. Peripheral B-cell counts declined below quantifiable limits in most patients, with a median time to B-cell depletion of 6.9 versus 7.0 days for DRL_RI versus MabThera.

Conclusion: The study demonstrated efficacy equivalence of DRL_RI to MabThera; with comparable safety, immunogenicity, serum concentrations, and PD between groups.

Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT03976102 and EudraCT (2018-004223-36).

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利妥昔单抗生物类似药（DRL_RI）与MabThera®治疗低肿瘤负荷滤泡性淋巴瘤的疗效和安全性：FLINTER研究

背景和目的：该III期研究(RI-01-006；FLINTER)研究表明，在未接受治疗的II-IV期、cd20阳性、低肿瘤负荷滤泡性淋巴瘤（LTB-FL）患者中，DRL_RI与欧盟批准的利妥昔单抗（MabThera®）的疗效相当。该研究还评估了DRL_RI与MabThera的安全性、免疫原性、利妥昔单抗浓度和药效学（PD）。设计和方法：先前未治疗的II-IV期cd20阳性LTB-FL患者（N = 317）随机（1:1）接受DRL_RI （N = 162）或MabThera （N = 155）静脉滴注375 mg/m²，每周4周（诱导期），此后每8周（第12周至第36周）（维持治疗），随访至第52周。主要终点是基于盲法独立中心评价的28周最佳总缓解率（BORR）。如果BORR差异的双侧90%置信区间（CI）在预定的等效范围内（±17%），则证明疗效等效。次要终点包括客观和完全缓解、缓解持续时间、无进展生存期、总生存期、安全性、免疫原性、平均血清浓度和PD。结果：截至第28周，DRL_RI组的BORR为80.2%，而MabThera组为79.4%；差异为0.89% (90% CI: -6.67 ~ 8.48；95% CI: -8.05至9.93，在预先规定的范围内)。两个治疗组在所有次要疗效终点上具有可比性。68.6%的患者报告了治疗后出现的不良事件；两组间的安全性、免疫原性和平均血清浓度相似。大多数患者的外周b细胞计数下降到可量化的限度以下，DRL_RI和MabThera的中位b细胞耗尽时间为6.9天，而MabThera为7.0天。结论：DRL_RI与MabThera疗效相当；两组间的安全性、免疫原性、血清浓度和PD相当。试验注册：该试验在ClinicalTrials.gov注册，识别码：NCT03976102和EudraCT（2018-004223-36）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Therapeutic Advances in Medical Oncology ONCOLOGY-

CiteScore

8.20

自引率

2.00%

发文量

160

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).