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    Home > Active Ingredient News > Antitumor Therapy > 2021EHA study express│Professor Zhang Huilai: Data analysis of the effectiveness and safety of the Phase II study (MAGNOLIA study) of Zebutinib in the treatment of relapsed and refractory marginal zone lymphoma

    2021EHA study express│Professor Zhang Huilai: Data analysis of the effectiveness and safety of the Phase II study (MAGNOLIA study) of Zebutinib in the treatment of relapsed and refractory marginal zone lymphoma

    • Last Update: 2021-06-22
    • Source: Internet
    • Author: User
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    The epidemic continues, academic supremacy, the annual top international oncology conference, the 26th European Hematology Annual Conference (EHA) online conference in 2021 is underway.
    This conference will be held from June 9th to June 17th.
    BeiGene, a domestic innovative drug research and development company, today announced the effectiveness and safety data analysis of the Phase II study (MAGNOLIA study) of Zebutinib in the treatment of relapsed and refractory (R/R) marginal zone lymphoma (MZL)
    .

     Research background Marginal zone lymphoma is a highly heterogeneous lymphoma, and there is no uniform treatment plan
    .

    Patients with advanced marginal zone lymphoma often cannot be cured, and B cell receptor-mediated signal transduction has been identified as a key step in the pathogenesis of MZL
    .

    Zebutinib (BGB-3111) is a powerful and highly specific new-generation BTK inhibitor.
    It is a BTK inhibitor that can maximize the inhibition of BTK while seldom affecting the TEC and EGFR family kinases.
    Inhibition of other targets can be considered as off-target effects and is related to atrial fibrillation, thrombocytopenia and bleeding events
    .

    Research methods The MAGNOLIA study (2021 EHA EP783) is a multi-center, phase 2, single-arm study.
    The study included adult patients with R/R MZL who had received at least one CD20-based induction therapy before
    .

    All enrolled patients were given zebutinib 160 mg twice daily until disease progression or unacceptable toxicity
    .

    Long-term antiplatelet and anticoagulant drugs are allowed during the trial
    .

    The primary endpoint is the overall response rate (ORR) determined by the Independent Review Committee (IRC) according to LUGANO criteria
    .

    Secondary endpoints include ORR, duration of response (DOR), progression-free survival (PFS), and safety assessed by the investigator
    .

    (Picture: MAGNOLIA study trial design) (Picture: MAGNOLIA study baseline characteristics) The results of the study as of January 11, 2021, 68 people were enrolled
    .

    The median age is 70 years (range 37-95 years), and 28% of patients are ≥75 years old
    .

    Subtypes include extranodal type (mucosa-associated lymphoid tissue; 38%), lymph node type (38%), splenic type (18%), and undetermined MZL (6%)
    .

    The median number of treatment lines is 2 (range 1-6)
    .

    (Illustration: Evaluation of the efficacy of MAGNOLIA study IRC and INV) (Illustration: summary of results of various types of MAGNOLIA study) The median sustained exposure time of the drug is 59.
    1 weeks (range 3.
    7-84.
    1 weeks)
    .

    The efficacy of 66 patients can be evaluated
    .

    With a median follow-up of 15.
    7 months (1.
    6-21.
    7 months), the ORR (CR+PR) assessed by IRC was 68.
    2% (CR 25.
    8%, PR 42.
    4%), and the ORR (CR+PR) assessed by the investigator was 74% (CR 24%, PR 50%)
    .

    Responses were observed in all subtypes.
    The ORRs for extranodal, lymph node, splenic, and uncertain subtypes were 64%, 76%, 67%, and 50%, respectively
    .

    The CR rates of extranodal type, lymph node type, spleen type and uncertain subtype were 40%, 20%, 8%, and 25%, respectively
    .

    The median DOR and PFS were not reached; the 15-month PFS was 82.
    5%, and the 12-month DOR was 81%
    .

    (Graph: median follow-up of 15.
    7 months, PFS did not reach; 15 months PFS was 82.
    5%) (graphic: target lesion maximum diameter and vertical diameter product [SPD] change from baseline) (graphic: median follow-up 15.
    7 Months, DOR was not reached; 12-month DOR was 81%) (Figure: TEAEs summary) (Figure: ≥10% TEAEs) According to reports, the most common (≥10%) adverse event was diarrhea (22.
    1%) ), bruising (21%), thrombocytopenia (14.
    7%), constipation (14.
    7%), neutropenia (13.
    2%) and the like
    .

    Among 68 patients, 27 cases (39.
    7%) had grade 3 and above TEAE
    .

    Most of the adverse events were grade 1 and 2, and neutropenia was the most common (10%) AE of grade ≥3
    .

    Two patients died of new coronary pneumonia, and one patient died of myocardial infarction
    .

    These deaths have nothing to do with Zebutinib
    .

    Adverse events of concern also included all grades of neutropenia (13%), thrombocytopenia (13%), atrial fibrillation/flutter (3%), and hypertension (3%)
    .

    There are no reports of major bleeding/severe bleeding
    .

    There was no reduction in Zebutinib due to AEs
    .

    Research conclusions Zebutinib showed a high response rate and durable disease control in a phase II trial of relapsed and refractory marginal zone lymphoma (MAGNOLIA study), and has good safety
    .

    Professor Zhang Huilai commented that MZL is an indolent lymphoma with a long median survival time and significant heterogeneity
    .

    At present, immunochemotherapy can bring good curative effects, but there are still unmet needs for treatment, how to improve the long-term survival benefits of patients and how to reduce the long-term toxicity of therapeutic drugs
    .

    The emergence of targeted drugs, especially BTK inhibitors, has brought more treatment options for MZL patients, such as high tumor burden, elderly people who are not suitable for chemotherapy, and patients with early relapse or drug resistance after immunochemotherapy, and BTK inhibitors will be combined in the future The treatment may bring about survival improvement
    .

    Previous single-agent data showed that the ORR of the first-generation BTK inhibitor ibrutinib was 48% in treated MZL, and the median PFS was 14.
    2 months
    .

    The MAGNOLIA study showed that the ORR assessed by IRC was 68.
    2%, and the CR was 25.
    8%; remission was seen in all MZL subgroups; median follow-up time was 15.
    5 months, median DOR and PFS were not reached; 15-month PFS was 82.
    5 %
    .

    As a new generation of innovative products with specific structural modifications, Zebutinib has been approved by the FDA.
    It has higher target selectivity and higher drug exposure, which may bring better efficacy and safety, and provide it for the majority of MZL patients.
    Better treatment options
    .

    Professor Zhang Huilai Doctor of Oncology, Chief Physician, Doctoral Supervisor, Currently Director of Lymphoma Department of Cancer Hospital of Tianjin Medical University, Deputy Chairman of Lymphoma Professional Committee of Chinese Anti-Cancer Association, Chinese Society of Clinical Oncology (CSCO) Standing Committee of Anti-Lymphoma Alliance, China Healthcare Vice Chairman of the Oncology Branch of the International Exchange Promotion Association Vice Chairman of the Lymphoma Professional Committee of the Chinese Geriatric Healthcare Association Member of the Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Oncology and Cardiology Committee Member of the Lymphoma Group of the Oncology Branch of the Chinese Medical Association Chinese Anti-Cancer Association Member of the Integrated Oncology and Cardiology Committee, Chairman of the Lymphoma Professional Committee of Tianjin Anti-Cancer Association, Vice Chairman of Tianjin Blood Disease Quality Control Center, Vice Chairman of Tianjin Medical Association Hematologist Branch References: 1.
    Seiler T, Dreyling M Expert Opin Investig Drugs.
    2017;26(8):909-915.
    2.
    Becnel MR, Nastoupil LJ,Samaniego F, et al.
    Lenalidomide plus rituximab (R2) in previously untreatedmarginal zone lymphoma: subgroup analysis and long-term follow-up of anopen-label phase 2 trial.
    Br J Haematol.
    2019;185:874–882.
    3.
    Iannitto E, Bellei M,Amorim S,et al.
    Efficacy of bendamustine and rituximab in splenic marginal zonelymphoma: results from the phase II BRISMA/IELSG36 study.
    Br J Haematol.
    018;183:755–765.
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