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    Home > Active Ingredient News > Blood System > JAMA Oncology Shanghai Jiaotong University and other institutions cooperated, Academician Pei Zhengkang revealed that dasatinib is more effective in treating children with Philadelphia chromosome-positive acute lymphoblastic leukemia

    JAMA Oncology Shanghai Jiaotong University and other institutions cooperated, Academician Pei Zhengkang revealed that dasatinib is more effective in treating children with Philadelphia chromosome-positive acute lymphoblastic leukemia

    • Last Update: 2021-08-10
    • Source: Internet
    • Author: User
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    Editor’s note iNature is China’s largest academic official account.
    It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
    The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
    .

    iNature requires a randomized clinical trial to determine whether the second-generation Abl-tyrosine kinase inhibitor dasatinib (dasatinib) is better than the first-generation inhibitor imatinib mesylate in the treatment of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) is more effective
    .

    On January 16, 2020, Shanghai Jiaotong University, Chongqing Medical University, Soochow University, Fudan University, Shengshude Children’s Research Hospital and other units cooperated.
    Academician Ching-Hon Pui was online at JAMA Oncology (IF=31.
    78) Published a research paper entitled "Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia, A Randomized Clinical Trial".
    This open-label phase 3 randomized clinical trial was conducted in 20 hospitals in China
    .

    The inclusion period is from January 1, 2015 to September 18, 2018
    .

    Patients from 0 to 18 years of age were recruited
    .

    Of the 225 confirmed patients, 35 refused to participate, one died before treatment, and the remaining 189 patients were available for analysis
    .

    The data analysis time is from January 1st to August 4th, 2019
    .

    Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) for the entire duration of ALL treatment from the diagnosis during remission induction to the end of continued treatment
    .

    The main result is event-free survival, which is analyzed according to intention to treat
    .

    Secondary outcomes are recurrence, death due to toxic effects, and overall survival
    .

    In 189 participants (136 males [72.
    0%]; median age was 7.
    8 [interquartile range (IQR), 5.
    2-11.
    3] years) and a median follow-up of 26.
    4 (IQR, 16.
    3-34.
    1) months, The 4-year event-free survival rate and overall survival rate of the dasatinib group were 71.
    0% (95% CI, 56.
    2%-89.
    6%) and 88.
    4% (95% CI, 81.
    3%-96.
    1%), respectively.
    Imatinib The 4-year event-free survival rate and overall survival rate of the group were 48.
    9% (32.
    0%-74.
    5%; P = .
    005, log-rank test) and 69.
    2% (95% CI, 55.
    6%-86.
    2%; P =.
    04, log-rank test)
    .

    The 4-year cumulative risk of any recurrence in the dasatinib group was 19.
    8% (95% CI, 4.
    2%-35.
    4%), and 34.
    4% (95% CI, 15.
    6%-53.
    2%) in the imatinib group (P =.
    01, Gray test), while the 4-year cumulative risk of solitary central nervous system recurrence in the dasatinib group was 2.
    7% (95% CI, 0.
    0%-8.
    1%) and 8.
    4% (95% in the imatinib group) CI, 1.
    2%-15.
    6%, P = .
    06, Gray test)
    .

    There was no significant difference in the frequency of severe toxic effects between the two treatment groups
    .

    In conclusion, in the treatment of chromosome-positive ALL in Philadelphia, intensive chemotherapy of 80 mg/m2 of dasatinib per day produced superior results than that of imatinib mesylate 300 mg/m2 per day.
    In the absence of preventive cranial radiation therapy In the case of, it has a good control effect on the leukemia of the central nervous system
    .

    The Philadelphia chromosome occurs in approximately 3% to 4% of childhood acute lymphoblastic leukemia (ALL) cases
    .

    Historically, it has been associated with a worse prognosis, with a 5-year event-free survival rate of 28% to 32%
    .

    The addition of the first-generation Abl-tyrosine kinase inhibitor imatinib mesylate increased the 5-year event-free survival rate to 57%, but almost all patients received craniocerebral irradiation, ranging from 38% to 100% Of patients received a transplant
    .

    Because relapse and drug resistance are relatively common events in patients treated with imatinib, two second-generation tyrosine kinase inhibitors, dasatinib and nilotinib hydrochloride, were developed.
    ) To overcome mutations in the kinase domain of ABL1 (OMIM 189980) that induce resistance
    .

    Dasatinib is the more commonly used dual Abl/Src kinase inhibitor and can cross the blood-brain barrier to eradicate central nervous system (CNS) leukemia
    .

    Several non-randomized clinical trials have shown that dasatinib can ensure results comparable to those achieved by imatinib, although the proportion of patients receiving allotransplantation or craniocerebral irradiation is low
    .

    Due to the significant differences in the use of historical controls and the proportion of patients receiving transplantation and craniocerebral irradiation in these trials, the relative efficacy of imatinib and dasatinib remains uncertain
    .

    The study reports the early results of the first randomized clinical study to compare the efficacy of imatinib and dasatinib on Philadelphia chromosome-positive ALL children
    .

    This open-label phase 3 randomized clinical trial was conducted in 20 hospitals in China
    .

    The inclusion period is from January 1, 2015 to September 18, 2018
    .

    Patients from 0 to 18 years of age were recruited
    .

    Of the 225 confirmed patients, 35 refused to participate, one died before treatment, and the remaining 189 patients were available for analysis
    .

    The data analysis time is from January 1st to August 4th, 2019
    .

    Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) for the entire duration of ALL treatment from the diagnosis during remission induction to the end of continued treatment
    .

    The main result is event-free survival, which is analyzed according to intention to treat
    .

    Secondary outcomes are recurrence, death due to toxic effects, and overall survival
    .

    In 189 participants (136 men [72.
    0%]; median age was 7.
    8 [interquartile range (IQR), 5.
    2-11.
    3] years) and a median follow-up of 26.
    4 (IQR, 16.
    3-34.
    1) months, The 4-year event-free survival rate and overall survival rate of the dasatinib group were 71.
    0% (95% CI, 56.
    2%-89.
    6%) and 88.
    4% (95% CI, 81.
    3%-96.
    1%), respectively.
    Imatinib The 4-year event-free survival rate and overall survival rate of the group were 48.
    9% (32.
    0%-74.
    5%; P = .
    005, log-rank test) and 69.
    2% (95% CI, 55.
    6%-86.
    2%; P =.
    04, log-rank test)
    .

    The 4-year cumulative risk of any recurrence in the dasatinib group was 19.
    8% (95% CI, 4.
    2%-35.
    4%), and 34.
    4% (95% CI, 15.
    6%-53.
    2%) in the imatinib group (P =.
    01, Gray test), while the 4-year cumulative risk of solitary central nervous system recurrence in the dasatinib group was 2.
    7% (95% CI, 0.
    0%-8.
    1%) and 8.
    4% (95% in the imatinib group) CI, 1.
    2%-15.
    6%, P = .
    06, Gray test)
    .

    There was no significant difference in the frequency of severe toxic effects between the two treatment groups
    .

    In conclusion, in the treatment of chromosome-positive ALL in Philadelphia, intensive chemotherapy of 80 mg/m2 of dasatinib per day produced superior results than that of imatinib mesylate 300 mg/m2 per day.
    In the absence of preventive cranial radiation therapy In the case of, it has a good control effect on the leukemia of the central nervous system
    .

    Statement: This study is a clinical trial and does not constitute medication guidance.
    Please follow the doctor's instructions for specific medication
    .

    Reference message: https://jamanetwork.
    com/journals/jamaoncology/fullarticle/2758575
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