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    Home > Active Ingredient News > Blood System > 9.22 International Chronic Granules Professor Jiang Qian: The third generation of TKI drugs in China is expected to break the predicament of drug resistance and benefit more patients

    9.22 International Chronic Granules Professor Jiang Qian: The third generation of TKI drugs in China is expected to break the predicament of drug resistance and benefit more patients

    • Last Update: 2021-10-01
    • Source: Internet
    • Author: User
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    Chronic myeloid leukemia (CML, hereinafter referred to as chronic myeloid) is a malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells.
    It is caused by the ectopic production of fusion genes at the ends of chromosomes 9 and 22 in the body.
    September 22 This is where the "International Slow Grain Day" came from [1]
    .

    (Image source:In the era of conventional chemotherapy, the prognosis of patients with CML is very poor, and almost all patients die of leukemia[2]
    .

    After the advent of tyrosine kinase inhibitors (TKI) 20 years ago, the prognosis of patients with chronic particles has been greatly improved, and the 10-year survival rate is close to 90% [3]
    .

    However, about 10% of patients will develop resistance or disease progression
    .

    How to break the predicament of drug resistance, solve the survival pain points of this small number of patients, and make CML truly turn into a controllable and curable "chronic disease" has become the goal of researchers' exploration
    .

     On the occasion of the 20th anniversary of the "International CML Day" and targeted therapy, Professor Jiang Qian, deputy director of the Department of Hematology, Peking University People's Hospital, conducted popular science on the knowledge of chronic particles and the current status of diagnosis and treatment
    .

    She mentioned, “China’s CML diagnosis and treatment level is the same as the international level, but patients who are resistant or intolerant to the first and second generation TKIs lack third-generation TKI drugs
    .

    A new third-generation TKI drug independently developed by China—oribati Olverembatinib (HQP1351, formerly known as Nectinib and Oribatinib) has been in clinical trials for 5 years.
    In the current follow-up period, the efficacy is significant and the toxicity is tolerable
    .
    The
    drug has been submitted in China.
    Listing application and included in priority review
    .

    It is hoped that the drug will be marketed as soon as possible and will benefit more patients
    .

    "TKI drugs have turned chronic particles into chronic diseases.
    The 10-year survival rate is close to 90%.
    Chronic particles are one of the main diseases of leukemia, accounting for 15% of adult leukemia, and the global annual incidence rate is 1.
    6 to 2 per 100,000 [3, 4]
    .
    There
    are relatively more CML patients in China, and statistics show that the number of new-onset patients in China accounts for 38% of the 8 major countries in China, the United States, Japan and Europe
    .
    [5]
    In addition, CML patients in China are younger than those in the West.
    epidemiological surveys in several regions of the country show CML the median age of onset is 45 to 50 years, while the median age in Western countries CML was 67 years [3]
    .

     CML is the first to be proved and chromosomal abnormalities Of human tumors, due to the translocation of chromosomes 9 and 22 in the patient’s body, resulting in the formation of a new BCR-ABL fusion gene
    .

    This fusion gene expresses a unique 210kDa tyrosine phosphoprotein kinase (p210BCR-ABL) [ 1]
    .

    prior tyrosine kinase inhibitor appears unsatisfactory efficacy of traditional chemotherapy, bone marrow transplant conditions harsh, poor prognosis of patients with CML, 10-year survival rate of less than 20% [6]
    .

    2001 The first TKI drug to be approved internationally marked the entry of a targeted era of CML therapy.
    Since then, the prognosis of CML patients has been greatly improved, and the 10-year survival rate has increased to 85-90% [3]
    .

    TKI drugs have also become international and domestic The first-line and later-line treatments for CML recommended by multiple guidelines [3,4]
    .

     "After 20 years, TKI drugs have completely changed the course and treatment outcome of CML patients
    .

    Chronic granule is transforming from a malignant hematological tumor into a chronic disease similar to hypertension and diabetes
    .

    The treatment demands of patients with chronic particles have also changed from obtaining long-term survival to improving the quality of life
    .

    "Professor Jiang Qian said
    .
    The
    third generation of TKI welcomes breakthroughs and is expected to provide new solutions to the drug resistance problem.
    Although most patients with chronic particles can benefit from TKI drug treatment, some patients can even achieve treatment free remission.
    Remission, TFR), but still about 10% of patients will develop resistance or disease progression, acquired resistance has become the main challenge of chronic particle therapy
    .

    BCR-ABL kinase region mutation is an important mechanism of acquired resistance, of which T315I mutation is the most common type of resistance mutations, not only the high incidence of mutations (10-27%), but also a second-generation TKI resistance are leading to this kind of disease in patients with rapid progression and poor prognosis [7]
    .

     for For patients with drug resistance or poor curative effect and advanced chronic particles, especially for patients with T315I mutation, the new generation of TKI drugs is "just needed", but there is no third-generation TKI drug in China
    .
    For
    patients with T3151 mutation Unmet demand, a new third-generation TKI drug, oribatinib, has been developed in China
    .

     A clinical trial led by Professor Jiang Qian to treat oribatinib in chronic myeloid leukemia with previous TKI resistance The efficacy and safety of TKI were analyzed
    .
    The
    study has been 5 years since the first patient was enrolled in October 2016, and more than 200 patients were enrolled, of which 70-80% of patients experienced more than two types of TKI Drug resistance
    .
    The
    results show that in chronic phase patients, 60%-70% of patients have chromosomes turned negative, and one-third of patients have achieved a major molecular response (MMR), which means that their disease is very stable
    .

    And it is accelerating.
    Among the patients at the first stage, 80% of the patients’ blood picture was controlled, and half of the chromosomes became negative
    .

    It can be said that oribatinib has significant clinical efficacy in patients with first- and second-generation TKI resistance and multi-drug resistance, and its toxicity is tolerable
    .

    The study has been selected as an oral report by the American Annual Meeting of Hematology (ASH) for three consecutive years, and has been nominated for the "Best Research" at the 2019 ASH Annual Meeting
    .

     Professor Qian Jiang said: "The current trial population of Orebatinib is CML patients who have undergone first- and second-generation TKI resistance, or multi-drug resistance, but this drug targets the BCR-ABL gene.
    In theory, It can also be applied to Philadelphia chromosome-positive acute leukemia
    .
    It
    is very much hoped that the drug will be marketed as soon as possible, so that more patients will benefit from it
    .

    "It is understood that at present, Ascent Pharma’s oribatinib has submitted a new drug application in China.
    , And was included in the priority review and breakthrough treatment varieties
    .

    It is believed that with the introduction of new drugs and the standardization of kinase mutation detection, the existing drug resistance problem is expected to be overcome and more patients can benefit from it
    .

    Experts call for a "normal" treatment of CML patients and help them return to society.
    With the widespread use of TKI, the survival period of chronic granule patients is close to that of normal people of the same age, and more and more studies have begun to pay attention to the quality of life of patients
    .

    The quality of life is not only reflected in the physical and mental condition, but also in the return to society
    .

    According to Professor Jiang Qian’s own experience in medical consultations: Although the disease has been well controlled, many young patients still hide their condition, worrying that once they become public, they will be viewed from another perspective, which will cause resistance to their advancement to school and job hunting.

    .

     "The desire of CML patients to return to society and their desire to be accepted is very strong.
    There are many outstanding CML patients who have made important contributions to their work.
    These people should be regarded as normal people!" Professor Jiang Qian called for Patients with chronic particles should not only pay attention to disease management, but also accept them from the heart so that they can work and live normally
    .

    At the same time, patients with CML are encouraged to actively speak up, so that more people can understand the real life of CML
    .

    I hope that all sectors of society will actively contribute their efforts and work together to help patients with chronic particles rebuild their confidence in life and return to the "big family" of society! "Professor Jiang Qian, Doctor of Medicine, Chief Physician, Professor, PhD Supervisor, Deputy Director, Department of Hematology, Peking University People's Hospital, Member of the National Representative Committee of the International CML Foundation, Member of the Hematology Branch of the Chinese Medical Association, and Deputy Leader of the Leukemia Lymphoma Group, Beijing Medical Association Hematology Branch Designated Chairman, Chinese Medical Education Association Leukemia Branch Chairman, China Medical Education Association Hematology Branch Deputy Chairman Leukemia Research, Chinese Journal of Hematology, Chinese Journal of Experimental Hematology, Journal of Clinical Hematology Editorial Board Reference: [1 ] KaushanskyK, Marshall AL, Prchal JT, et al.
    Williams Hematology (9th edition) [M], Chen Zhu, Chen Saijuan, main translation.
    Beijing: People's Medical Publishing House, 2018: 1311-1345.
    [2] Baccarani M , Abruzzese E, Accurso V, et al.
    Managing chronic myeloid leukemia fortreatment-free remission: A proposal from the GIMEMA CML WP[J].
    Blood Advances,2019, 3(24):4280-4290.
    [3] Chinese Medical Association Chinese Journal of Hematology.
    Chinese Guidelines for Diagnosis and Treatment of Chronic Myeloid Leukemia (2020 Edition)[J].
    Chinese Journal of Hematology,2020,41(05): 353-364.
    [4] NCCNClinical Practice Guidelines in Oncology: Chronic Myeloid Leukemia, Version 1.
    2022-August 19, 2021.
    [5] Decision Resources Group 2017 data[6] Leukemia E.
    The price of drugs forchronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs:
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