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    Home > Active Ingredient News > Blood System > 2021 CSCO Professor Gong Tiejun: Progress in the treatment of acute lymphoblastic leukemia

    2021 CSCO Professor Gong Tiejun: Progress in the treatment of acute lymphoblastic leukemia

    • Last Update: 2021-10-22
    • Source: Internet
    • Author: User
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    The 24th National Conference on Clinical Oncology and the 2021 CSCO Annual Conference will be held on September 25-29, 2021.
    The theme of this conference is "Focus on Innovative Research, Leading the Original Future"
    .

    The conference continues to adhere to the fundamental purpose of CSCO, adopts new forms to actively carry out academic exchange activities in special periods, promotes academic exchanges and scientific and technological cooperation in the field of clinical oncology in China, encourages support for clinical research and innovation, and advocates multidisciplinary standardized comprehensive treatment based on Precision oncology actively promotes the development of the discipline
    .

    At the CSCO conference, Professor Gong Tiejun from Harbin Institute of Hematology and Tumor gave a theme report on "Acute Lymphoblastic Leukemia (ALL) Treatment Progress".
    Yimaitong organized the main contents as follows
    .

    Professor Gong Tiejun first gave a brief introduction to the basic situation and pathogenesis of ALL
    .

    ALL accounts for 10% of all leukemias.
    Adults have a lower incidence of ALL, 0.
    69 per 100,000; children are a high-risk population of ALL, with an incidence of 3.
    6 per 100,000
    .

    The multi-step specific genetic damage of lymphoid progenitor cells changes cell function, causing immature lymphocytes to proliferate and accumulate in the bone marrow, leading to the occurrence of ALL
    .

    Initial induction therapy can kill aggressive proliferating cells and selective or acquired mutant cells, but ALL cells that are not sensitive to chemotherapeutics can still cause disease recurrence
    .

    Progress in the treatment of relapsed and refractory ALL Professor Gong Tiejun said that there are still problems in the clinical treatment of current ALL patients, especially those with relapsed and refractory (R/R) ALL
    .

    The long-term survival of Philadelphia chromosome-negative (Ph-) R/R ALL patients needs to be improved
    .

    Relevant retrospective studies have shown that patients with R/R Ph-ALL have poor survival outcomes, with a median overall survival (OS) of only 3.
    3 months and a 1-year OS rate of only 22%-24%
    .

    Although tyrosine kinase inhibitors (TKI) have brought long-term disease remission for Ph+ ALL patients, the long-term survival rate of Ph+ ALL patients who relapsed after TKI treatment is also poor, with a median OS of only 5-9 months, 1 year The OS rate is less than 40%
    .

     In recent years, immunotherapy has made some progress in ALL
    .

    At present, the immunologic drugs and therapies used in the treatment of ALL are mainly divided into two categories: monoclonal antibody drugs (including single-target monoclonal antibodies, bispecific antibodies, antibody-drug conjugates) and cell therapies (such as chimeric antigen receptors).
    Somatic T cell [CAR-T] immunotherapy)
    .

    Among them, the world's first CD19/CD3 bispecific antibody, belintoomab, showed excellent efficacy in R/R ALL
    .

    The Phase III TOWER study compared the efficacy and safety of belintolumab and standard chemotherapy in the treatment of adult R/R Ph-ALL.
    The results of the study showed that belintolumab significantly prolonged the OS of patients with R/R ALL ( Median OS: 7.
    7 months vs 4.
    0 months; 6-month OS rate: 54% vs 39%; P=0.
    01)
    .

    For patients with R/R ALL who received salvage treatment for the first time, belintolumab reduced the risk of death, prolonged OS more than 2 times (11.
    1 months vs 5.
    5 months; P=0.
    016), and achieved higher Complete response (CR) rate (44% vs 29%)
    .

    In addition, belintoomab has good safety in the treatment of R/R ALL.
    The incidence of ≥3 grade adverse events (AE) is lower than that of the standard chemotherapy group.
    At the same time, the incidence of cytokine release syndrome (CRS) is low (4.
    9%) )
    .

    The safety of belintoomab in the Phase III clinical study carried out in China is basically the same as that of global studies, and the incidence of AEs ≥3 is low
    .

     CAR-T therapy tisagenlecleucel (tis-cel) also showed good efficacy in R/R ALL
    .

    The ELIANA study included patients with R/R ALL who had received a median of 3 salvage treatments and received tis-cel treatment.
    The results of the study showed that tis-cel treatment of R/R ALL had CR/complete remission with incomplete hematological recovery (CRi ) The rate reached 81%, among which patients with minimal residual disease (MRD) who achieved disease remission were all negative
    .

    The 1-year event-free survival (EFS) rate for Tis-cel treatment of R/R ALL was 50%, and the 1-year OS rate was 76%
    .

    However, 73% of grade 3-4 AEs in the study were related to CAR-T treatment, 77% of patients developed CRS, and 48% of patients received tocilizumab treatment.
    Therefore, attention should be paid when using tis-cel to treat R/R ALL.
    AE management
    .

    MRD positive ALL treatment progress MRD is an important indicator for predicting the prognosis of ALL patients
    .

    Relevant studies have shown that the 5-year hematological recurrence rate of MRD-positive ALL patients is as high as 56%-100%, while MRD-negative ALL patients are only 18%-33%.
    MRD status also exists for CR status, EFS, and OS in ALL patients.
    Influence
    .

    The current domestic and foreign guidelines clearly point out that MRD positive status indicates a high risk of recurrence, and continuous monitoring of the MRD status of ALL patients is required
    .

     The BLAST study is the first ALL international multicenter clinical study with MRD as the endpoint.
    The study included 116 patients with ALL who were treated with belintoxumab
    .

    The results of the study showed that belintoomab can clear MRD quickly and efficiently, and 78% of patients reached MRD-negative status in the first cycle of treatment
    .

    Subgroup analysis showed that the realization of MRD negative by belintolumab was not affected by age, disease burden, and number of treatment lines
    .

    The 5-year long-term follow-up results of the study showed that belintoomab can provide long-term survival benefits for MRD-positive ALL patients, with a median OS of 36.
    5 months and a 5-year OS rate of 43%
    .

    Compared with patients who did not reach MRD-negative status in the first cycle of treatment, patients who reached MRD-negative status after the first cycle of belintoxumab treatment had significantly higher OS (median OS: not reached vs 14.
    4 months; P=0.
    002 )
    .

    In addition, regardless of whether MRD-positive ALL patients receive transplantation, belintoomab can provide long-term survival benefits
    .

    The treatment of newly diagnosed ALL has progressed.
    Immunotherapy has also shown good curative effect in newly diagnosed ALL
    .

    A study compared the efficacy of Mini-hyper-CVD regimen combined with antibody drug conjugate Inotuzumab ozogamicin and Hyper-CVD regimen in the treatment of newly diagnosed elderly (>60 years) Ph-ALL patients
    .

    The results of the study showed that the CR rate of the combined treatment of newly diagnosed elderly ALL reached 98%, and the MRD negative rate reached 96%
    .

    Compared with the Hyper-CVD program, the 3-year EFS rate (49% vs 29%; P=0.
    001) and the 3-year OS rate (54% vs 32%; P=0.
    002) of the combined program were significantly higher
    .

     Another study explored the efficacy of Hyper-CVAD regimen followed by belintoux in the first-line treatment of newly diagnosed adult patients with Ph-B-ALL
    .

    The results of the study show that the combined program can achieve deep disease remission for newly diagnosed ALL patients.
    After induction therapy, the CR rate reached 81%, the MRD negative rate reached 71%, the 2-year recurrence-free survival (RFS) rate reached 71%, and the 2-year OS The rate reaches 80%
    .

     For newly diagnosed Ph+ ALL patients, the second-generation TKI dasatinib combined with belintolumab without chemotherapy can be used as a consolidation treatment option after first-line treatment
    .

    The results of a related phase II study showed that at a median follow-up of 18 months, the OS rate of ALL patients reached 95%, the disease-free survival (DFS) rate reached 88%, and the cumulative recurrence rate was only 8%
    .

    The program is safe in newly diagnosed ALL patients, with fewer grades ≥3 AEs
    .

    Summary Professor Gong Tiejun concluded: At present, ALL treatment has entered the era of immunotherapy, and immunological drugs and therapies such as bispecific antibodies, antibody-drug conjugates, and CAR-T therapy have been applied in ALL treatment
    .

    Immune drugs represented by belintuomab have shown excellent efficacy in R/R ALL and MRD-positive ALL
    .

    Related immunotherapy programs also provide new treatment options for newly diagnosed ALL, which is expected to open a "chemo-free era" for newly diagnosed ALL
    .

    Professor Gong Tiejun, Director of the Third Hematology Ward, Harbin Institute of Hematology and Cancer, Deputy Chief Physician, Member of the Youth Committee of the Chinese Medical Association Hematology Branch, Deputy Chairman of the Youth Committee of the CSCO Anti-Leukemia and Lymphoma Alliance, Secretary of the CSCO Anti-Leukemia Alliance Expert Committee, CSCO Anti-Lymphoma Alliance Expert Committee Member, Multiple Myeloma Professional Committee, Chinese Medical Doctor Association Member, Tissue Cell Disease Professional Committee, Chinese Medical Doctor Association Member, Myeloidology Group, Hematology and Tumor Committee, Chinese Anti-Cancer Association, is mainly engaged in clinical work on leukemia and myeloma.
    We make progress together
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