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
{"title":"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","authors":"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","doi":"10.1177/17588359251339925","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>This phase III study (RI-01-006; FLINTER) was conducted to demonstrate equivalent efficacy of DRL_RI to EU-approved rituximab (MabThera<sup>®</sup>) 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.</p><p><strong>Design and methods: </strong>Previously untreated, stage II-IV, CD20-positive LTB-FL patients (<i>N</i> = 317) were randomized (1:1) to receive DRL_RI (<i>n</i> = 162) or MabThera (<i>n</i> = 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>The study demonstrated efficacy equivalence of DRL_RI to MabThera; with comparable safety, immunogenicity, serum concentrations, and PD between groups.</p><p><strong>Trial registration: </strong>This trial was registered at ClinicalTrials.gov identifier: NCT03976102 and EudraCT (2018-004223-36).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251339925"},"PeriodicalIF":4.3000,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104602/pdf/","citationCount":"0","resultStr":"{\"title\":\"Efficacy and safety of rituximab biosimilar (DRL_RI) versus MabThera<sup>®</sup> in low-tumor-burden follicular lymphoma: the FLINTER study.\",\"authors\":\"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\",\"doi\":\"10.1177/17588359251339925\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>This phase III study (RI-01-006; FLINTER) was conducted to demonstrate equivalent efficacy of DRL_RI to EU-approved rituximab (MabThera<sup>®</sup>) 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.</p><p><strong>Design and methods: </strong>Previously untreated, stage II-IV, CD20-positive LTB-FL patients (<i>N</i> = 317) were randomized (1:1) to receive DRL_RI (<i>n</i> = 162) or MabThera (<i>n</i> = 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>The study demonstrated efficacy equivalence of DRL_RI to MabThera; with comparable safety, immunogenicity, serum concentrations, and PD between groups.</p><p><strong>Trial registration: </strong>This trial was registered at ClinicalTrials.gov identifier: NCT03976102 and EudraCT (2018-004223-36).</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"17 \",\"pages\":\"17588359251339925\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-05-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104602/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359251339925\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359251339925","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Efficacy and safety of rituximab biosimilar (DRL_RI) versus MabThera® in low-tumor-burden follicular lymphoma: the FLINTER study.
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).
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).
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