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    Home > Active Ingredient News > Blood System > Roundtable pie to inventory the most common types of leukemia acute myeloid leukemia treatment, the efficacy of the improvement "future can be expected"

    Roundtable pie to inventory the most common types of leukemia acute myeloid leukemia treatment, the efficacy of the improvement "future can be expected"

    • Last Update: 2022-10-14
    • Source: Internet
    • Author: User
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    Acute myeloid leukemia (AML) is a highly heterogeneous malignant hematologic tumor and is the most common type of acute leukemia in adults [1
    ].
    Traditional treatments include chemotherapy and hematopoietic stem cell transplantation, but the recurrence rate is more than 50% and the overall survival rate is less than 50% [2
    ].
    Treatment of AML is urgently needed for further development
    .
    Professor Li Daqi, Director of the Department of Hematology of the Affiliated Central Hospital of Shandong First Medical University, Professor Xu Hongzhi, Director of the Department of Hematology of Shandong Provincial Hospital, Professor Zhang Hao, Director of the Department of Hematology of the Affiliated Hospital of Jining Medical College, Professor Zhang Haiyan, Director of the Department of Hematology of Linyi People's Hospital, and Professor Xiao Taiwu, Director of the Department of Hematology of Liaocheng People's Hospital, were invited to discuss the current situation of acute myeloid leukemia treatment and look forward to the new trend
    of AML treatment.



    01


    Prof.
    Daqi Li: Traditional treatment methods combined with new treatment methods have significantly improved the efficacy of AML

    AML is one of the most concerned diseases by hematologists and the most challenging
    .
    In recent years, with the application of new targeted drugs and biological therapies combined with traditional chemotherapy and hematopoietic stem cell transplantation, the efficacy of AML has improved
    significantly.
    Among them, chemotherapy is still the basic treatment method of AML; Targeted drugs make up for the needs of patients who are not suitable for intensive therapy, significantly improve the prognosis of such patients, and improve patient survival; Biological therapy is effective in refractory patients with TP53 positive; Hematopoietic stem cell transplantation, which includes autologous hematopoietic stem cells and allogeneic hematopoietic stem cells, is a key treatment method for AML, and autologous hematopoietic stem cell transplantation is available for patients with a good prognosis and an intermediate prognosis (negative for small residual lesions after treatment), while allogeneic hematopoietic stem cell transplantation is required for patients with poor prognosis
    .
    Although the combination of new targeted drugs with traditional chemotherapy and hematopoietic stem cell transplantation has made great progress in the treatment of AML, it still needs to be refined
    .
    How to better carry out AML maintenance therapy also needs further research and discussion [3,4].


    02

    Professor Xu Hongzhi: Clarify the therapeutic significance of hematopoietic stem cell transplantation and continuously optimize the treatment plan

    In recent years, with the deepening of research on AML, the development of targeted drugs has injected fresh blood into the treatment of AML
    .
    So, how should the treatment plan of AML be selected at this stage? Will targeted drugs replace conventional chemotherapy? Is transplant treatment still necessary? These are all questions
    that clinicians need to consider.


    The new targeted drugs do not replace traditional chemotherapy, but only complement and improve
    them.
    For young AML patients, chemotherapy or even hematopoietic stem cell transplantation is still needed to be cured
    .
    Hematopoietic stem cell transplantation is still one of the most effective ways to treat AML, and factors that affect the efficacy of AML transplantation include pretreatment protocol, grafts, and donor age [5].

    But as haplotype transplantation opens a new chapter where everyone is a donor, transplant mode is no longer a major factor
    affecting patient survival.
    Haplotype transplant therapy can be used as an alternative donor for medium- to high-risk AML transplantation and even as a first choice for
    some high-risk AML patients.
    Therefore, hematopoietic stem cell transplantation, which integrates immunology, molecular biology, cytogenetics and multi-clinical disciplines, has made great progress in both basic and clinical research in recent years, and is still the most effective cure for malignant blood diseases, severe bone marrow failure diseases and congenital genetic metabolic diseases [6,7].


    At the same time, the development of targeted drugs has made up for the treatment gap
    that is not suitable for patients with intense chemotherapy or transplantation.
    However, with the application of second-generation sequencing in the diagnosis and treatment of AML, the combined analysis of integrating multiple mutations is a development trend and a necessity for comprehensive and in-depth study of AML
    .
    [8] AML will enter an era of precision therapy in which traditional chemotherapy is combined with targeted therapies [8].

    03

    Professor Zhang Hao: AML induction therapy is the key, and a reasonable plan is selected "according to individual conditions"

    AML induction therapy is a critical stage
    in treatment.
    For patients aged < 60 years: national and international guidelines recommend standard dose IA or DA regimen; The 2017 China AML Guidelines recommended HA+ anthracycline regimens such as HAA, HAD, etc.
    The standard dose recommended by NCCN in 2020 is DA+GO (CD33 positive<b11>).


    For patients > age 60 years who are suitable for intensive therapy: standard dose of IA, DA or MA regimen is recommended; The 2017 China AML guidelines recommend small-dose chemotherapy such as CAG, HAG, etc
    .
    For patients who are not candidates for standard dose chemotherapy, guidelines recommend low-intensity chemotherapy, low-dose cytarabine, vinetok + AZA, or DEC [9,10
    ].


    At present, there are many small molecule targeted drugs for the treatment of AML
    .
    For different patients, there are corresponding treatment options:


    • Patients with fit: induction therapy is recommended based on intensive therapy;

    • In patients with FLT3 mutations, intensive therapy is combined with midotoline
      .

    • CD33-positive patients: intensive therapy in combination with GO [3].

    • Patients with t-AML or AML-MRC: CPX-351 is used, and the new drug combination regimen includes intensive therapy plus vinetoxyl, intensive therapy combined with the 2nd generation FLT3 inhibitor gerratinib, etc
      .

    • Patients with Unfit: with low-dose chemotherapy, the demethylated drug azacitidine in combination with vinetok can be selected;

    • Patients with IDH1 mutations can combine with avonib, azacitidine plus Selinizol, azacitidine plus vinetok, and sidaaniline
      .

    • Patients with Frail are advised to add reduced doses of chemotherapy to the best supportive care [11,12] (Table 1).




    Table 1 AML therapeutic drugs [13].

    04

    Professor Haiyan Zhang: AML therapy may enter the era of targeted and immunotherapy, and future treatment needs to be further optimized

    In recent years, with the continuous progress of molecular biology, the emergence of new drugs with various different mechanisms, such as BCL-2 inhibitors, FLT3 inhibitors, IDH1/IDH2 inhibitors, etc.
    , has significantly improved the prognosis of AML
    .
    Therefore, in the era of targeted and immunotherapy in AML, AML therapy needs to be further optimized
    in the future.

    • Young low-risk patients are mainly chemotherapy containing medium and high doses of cytarabine, and whether innovative targeted drugs can replace or change this mode needs to be further explored;

    • Patients with comorbidities or underlying disease intolerance to chemotherapy may be treated with an elderly AML regimen
      .

    • Young high-risk patients, relapse refractory, no transplant contraindications, the use of new targeted drugs or targeted drugs combined with demethylated drugs or targeted drugs combined with chemotherapy, and immunotherapy (CAR-T) to achieve remission (MRD-) as soon as possible after allogeneic stem cell transplantation, regular testing after transplantation, donor lymphocyte infusion (DLI), molecular targeted drugs or demethylated drugs to prevent recurrence;

    • Future innovative targeted drugs continue to emerge and may also replace transplants
      in medium- and high-risk patients.

    • In elderly and unfit patients with AML, more treatment strategies with the BCL-2 inhibitor Vinekla plus azacitidine or decitabine are used instead of previous low-dose-intensity treatments;

    • Therapy with specific molecular mutations can be combined with specific molecularly targeted drugs by Venecra;

    • In the future, the treatment of elderly AML may enter the chemo-free mode, and the emergence of new targeted drugs will improve the long-term survival of elderly AML patients [4,14
      ].

    At present, there are few data on maintenance therapy, and the significance of innovative targeted drugs alone or in combination with or in combination with each other in maintenance therapy is worth further exploration
    .
    In short, the optimization of the treatment plan for acute leukemia in the future is based on the continuous development of genetic testing, the further refinement of risk stratification, the emergence of new targeted drugs, the further maturity of immunotherapy, and the unremitting exploration of blood disease experts, so that the cure of "AML" can be expected
    .

    05

    Professor Xiao Taiwu: Precise and individualized treatment to maximize the benefits of elderly AML patients

    The incidence of AML in the elderly is increasing, and the prognosis is worse
    in younger patients due to the fact that older AML patients often have cytogenetic abnormalities, a history of blood diseases, and a combination of organ function decline.
    Elderly AML patients still face great risks and challenges
    when choosing chemotherapy drugs and courses.
    With the improvement of medical technology and the development of second-generation sequencing technology, more and more new drugs and new therapies are gradually applied to the treatment of elderly AML, which makes the treatment of leukemia patients more individualized and brings new hope to elderly AML patients (Table 2).

    Table 2 Individualized AML treatment for the elderly (selection of treatment options based on poor prognostic factors[15]


    In generally well-deserved elderly patients, induction chemotherapy with a standard regimen (cytarabine plus anthracycline) provides a higher rate of
    complete remission and accident-free survival.
    The first-line treatment regimen for elderly AML patients who cannot tolerate intensive induction therapy is based on demethylated compounds (HMAs), and the most commonly used HMAs in clinical practice are decitabine and azacitidine
    .
    At the same time, clinical studies have shown that BCL-2 inhibitors can induce apoptosis in AML cells and have a good synergistic effect
    with HMA.


    In addition, new drugs such as FLT3 inhibitors, Hedgehog pathway inhibitors, isocitrate dehydrogenase inhibitors, histone deacetylase inhibitors, etc.
    , have played a good role
    in the treatment of elderly AML.
    Other emerging cell immunotherapy, PD-1 targeted therapy, allogeneic hematopoietic stem cell transplantation, and more molecularly targeted drugs are also in further clinical trials, which are believed to bring a new round of dawn to the treatment of elderly AML patients [16,17].

    06

    Professor Li Daqi concluded

    With the deepening of research and the development of medicine, the treatment of AML patients has undergone tremendous changes, more and more new drugs have become the choice of a new generation in clinical practice, and the efficacy of more combination chemotherapy regimens has become more and more significant
    .
    Therefore, for AML patients, in the clinic, the patient's age, molecular abnormalities, drug resistance, economic background and other factors should be fully considered, and their individualized and layered treatment plans should be formulated and improved to obtain the best efficacy
    .

    Expert profile


    Professor Li Daqi


    M.
    D.
    Professor, Master Supervisor

    Chief Physician, Department of Hematology, Affiliated Central Hospital of Shandong First Medical University

    Vice Chairman of Hematology and Tumor Branch of Shandong Anti-Cancer Association

    Vice Chairman of Stem Cell and Cell Application Committee of Shandong Medical Doctor Association

    Vice Chairman of the Hematology Professional Committee of Shandong Geriatrics Society

    Vice Chairman of the Hematology Committee of Shandong Society of Immunology

    Director of Shandong Stem Cell Society

    Chairman of the Hematology Professional Committee of Jinan Medical Association

    He is a member of the Hematology Branch of Shandong Medical Association

    Standing Committee Member of Hematology Physician Branch of Shandong Medical Doctor Association


    Expert profile


    Professor Xu Hongzhi


    Deputy Director of the Department of Hematology, Shandong Provincial Hospital

    Vice Chairman of Shandong Hematology Branch of Chinese Medical Association

    Vice Chairman of the Hematology Physicians Branch of Shandong Medical Doctor Association

    He is the chairman of the grass-roots committee of the Hematology Physicians Branch of Shandong Medical Doctor Association

    Vice Chairman of the Hematology Professional Committee of Shandong Geriatrics Society

    Vice Chairman of the Laboratory Medicine Professional Committee of the Chinese Association of Integrative Traditional and Western Medicine Expert Committee on Experimental Diagnosis of Hematological Diseases

    He is a member of the Hematology Professional Committee of the Cross-Strait Medical and Health Exchange Association

    The first batch of well-known experts of Shandong Provincial Hospital "National Public Health Emergency Response Expert Database" experts and "Journal of Chronic Diseases" editorial board

    He has presided over a number of funded scientific research projects funded by the Natural Science Foundation of Shandong Province, Shandong Provincial Science and Technology Research Center, Shandong Provincial Health Department, etc.
    , won 5 provincial and ministerial scientific and technological achievement awards, 3 department-level scientific and technological achievement awards, trained more than 20 doctoral and master students, published more than 40 papers in SCI and national academic journals, and participated in the compilation of 5 academic monographs.



    Expert profile


    Professor Zhang Hao

    Director of the Department of Hematology, Affiliated Hospital of Jining Medical College

    Doctor of Medicine, Chief Physician, Master Supervisor

    He is a member of the 8th Youth Committee of the Hematology Branch of the Chinese Medical Association

    He is a member of the Experimental Diagnostics Group of the Hematology Branch of the Chinese Medical Association

    Member of the Chinese Society of Clinical Oncology (CSCO) Anti-Leukemia Alliance

    He is a member of the Stem Cell Engineering Technology Branch of the Chinese Society of Biomedical Engineering

    He is a member of the Hematology Branch of Shandong Medical Association

    Deputy Leader of the Transplantation Group of the Hematology Branch of Shandong Medical Association

    Member of the Standing Committee of Hematology Branch of Shandong Medical Doctor Association

    Vice Chairman of Lymphoma Branch of Shandong Anti-Cancer Association

    He presided over four provincial, departmental and municipal projects

    He has edited 4 books and published 7 SCI papers

    There are more than 30 core journals in China



    Expert profile

    Professor Zhang Haiyan


    Director of the Department of Hematology, Linyi People's Hospital

    Linyi City special contribution young experts

    He is a member of the Blood Disease Translational Medicine Professional Committee of the Chinese Anti-Cancer Association

    Member of Shandong Hematology Society

    Standing Committee Member of Shandong Society of Hematology

    Vice Chairman of the Grassroots Committee of the Branch of Shandong Society of Hematology

    Vice Chairman of the Hematology Professional Committee of Shandong Geriatrics Society

    Member of Shandong Anti-Cancer Association

    He is a member of the Shandong Association of Integrative Traditional Chinese and Western Medicine

    Chairman of Linyi Hematology Society

    Vice Chairman of Linyi Association of Integrative Traditional Chinese and Western Medicine

    Member of Linyi Anti-Cancer Association



    Expert profile

    Professor Xiao Taiwu


    Director of the Department of Hematology, Liaocheng People's Hospital

    Chief physician, master supervisor

    Director of the Office of the National Stem Cell Clinical Research Institute of Liaocheng People's Hospital

    He is a member of the Blood Disease Branch of Shandong Medical Association

    He is a member of the Hematology Branch of Shandong Medical Doctor Association

    Vice Chairman of Lymphoma Immunotherapy Branch of Shandong Research Hospital Association

    Vice Chairman of the Hematology Branch of Liaocheng Medical Association



    References: (swipe to view)


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    NAIR R,BALDAUF H M.
    New strategies to treat AML: novel insights into AML survival pathways and combination therapies[J].
    Leukemia, 2021, 35(2): 299-311.


    2.
    KENNEDY V E, SMITH C C.
    FLT3 mutations in acute myeloid leukemia: key concepts and emerging controversies[J].
    Front Oncol, 2020, 10.


    3.
     DiNardo CD.
    Which novel agents hold the greatest promise in AML? [J].
    Best Pract Res Clin Haematol.
    2019 ,32(4):101106.

    4.
    LONG Xinyi,HU Rong.
    Research Progress on Targeted Therapy for Acute Myeloid Leukemia[J].
    Modern Oncology Medicine,2022,30(15):2847-2850.


    5.
    Zhao Chen,Sun Yuqian,Xu Lanping,et al.
    Effect of haplotype hematopoietic stem cell recovery status before transplantation on prognosis of patients with acute myeloid leukemia[J].
    Chinese Journal of Hematology,2021,42(12):1030-1034.

    6.
    Yegin ZA, Dikyar A, Aydın Kaynar L,et al.
    Comparison of post-remission strategies in acute myeloid leukemia: Autologous hematopoietic stem cell transplantation versus consolidation chemotherapy[J].
    Hematol Rep.
    2020 Dec 2; 12(3):8380.


    7.
    Li Z,Liu Y,Wang Q,et al.
    Autologous Stem Cell Transplantation Is a Viable Postremission Therapy for Intermediate-Risk Acute Myeloid Leukemia in First Complete Remission in the Absence of a Matched Identical Sibling: A Meta-Analysis[J].
    Acta Haematol.
    2019; 141(3):164-175.


    8.
    Wang Weimin,Li Yafei,Sun Ling,et al.
    Comparison of mutant gene profiles in elderly and young adults with acute myeloid leukemia based on second-generation sequencing[J].
    Chinese Journal of Experimental Hematology,2020,28(01):12-17.


    9.
    Leukemia & Lymphoma Group, Chinese Society of Hematology,Chinese Medical Association.
    Chinese guidelines for the diagnosis and treatment of adult acute myeloid leukemia (not APL) (2020) [J].
    2020 Aug 14; 42(8):617-623.


    10.
    Leukemia Lymphoma Group, Hematology Branch of Chinese Medical Association.
    Chinese Guidelines for the Diagnosis and Treatment of Acute Myeloid Leukemia in Adults (Nonacute Promyelocytic Leukemia) (2017 Edition)[J].
    Chinese Journal of Hematology,2017,38(03):117-182.


    11.
    Stone RM, Mandrekar SJ, Sanford BL,et al.
    Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation[J].
    N Engl J Med.
    2017,377(5):454-464.


    12.
    Nikanjam M, Capparelli EV, Lancet JE, et al.
    Persistent cytarabine and daunorubicin exposure after administration of novel liposomal formulation CPX-351: population pharmacokinetic assessment[J].
    Cancer Chemother Pharmacol.
    2018,81(1):171-178.


    13.
    Ma Jiale,Ge Zheng.
    Recent advances in clinical research on therapeutic drugs for acute myeloid leukemia[J].
    Advances in Pharmacy,2022,46(06):455-470.


    14.
    Konopleva M, Pollyea DA, Potluri J, et al.
    Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia[J].
    Cancer Discov.
    2016,6(10):1106-1117.


    15.
    Zhang Bing,Zhang Donghua.
    Treatment strategy and progress of acute myeloid leukemia in the elderly[J].
    Medical Review,2011,17(06):883-886.


    16.
    DiNardo CD, Pratz K, Pullarkat V, et al.
    Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia[J].
    Blood.
    2019,133(1):7-17.


    17.
    Fathi AT, Erba HP, Lancet JE, et al.
    A phase 1 trial of vadastuximab talirine combined with hypomethylating agents in patients with CD33-positive AML[J].
    Blood.
    2018 Sep 13; 132(11):1125-1133.

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