Zhang G J, Gong X Y, Qiu S W, Zhou C L, Liu K Q, Lin D, Liu B C, Wei H, Wei S N, Li Y, Gu R X, Gong B F, Liu Y T, Fang Q Y, Mi Y C, Wang Y, Wang J X
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2021 Feb 14;42(2):109-115. doi: 10.3760/cma.j.issn.0253-2727.2021.02.004.
This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients. This prospective, single-arm, and open clinical study enrolled 30 adult Ph(+) ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS (=0.004) , HRFS (=0.049) , and event-free survival (EFS; =0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS (=0.030) and EFS (=0.010) in the SCT group were better than those in the chemotherapy group. The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph(+) ALL patients. ClinicalTrials.gov, NCT02523976.
本研究评估达沙替尼联合多药化疗方案治疗费城染色体阳性急性淋巴细胞白血病（Ph(+) ALL）患者的疗效和安全性。本前瞻性、单臂、开放性临床研究纳入了2016年1月至2018年4月在本研究中心新诊断并接受治疗的30例成年Ph(+) ALL患者。给予标准诱导化疗4周。然而，在诱导治疗中，从第8天开始持续给予达沙替尼（100 mg/d）直至整个治疗结束。适合进行异基因或自体干细胞移植（SCT）的患者在疾病评估为完全缓解时接受移植。所有30例患者在诱导化疗后均实现血液学完全缓解（HCR），其中70.0%（21/30）实现累积分子完全缓解（MCR）。对患者进行随访，中位随访时间为37.8个月（32.0 - 46.6）。3年总生存率（OS）和3年无血液学复发生存率（HRFS）分别为68.1%和61.6%。此外，分别有63.3%和43.3%的患者实现分子主要缓解和MCR。因此，60.0%的患者在6个月时实现MCR。在6个月内实现MCR的患者具有更好的OS（P = 0.004）、HRFS（P = 0.049）和无事件生存率（EFS；P = 0.001）。15例患者（50.0%）在首次HCR时接受了SCT。然而，SCT组的HRFS（P = 0.030）和EFS（P = 0.010）优于化疗组。达沙替尼联合多药化疗方案被证明在治疗新诊断的成年Ph(+) ALL患者中安全有效。ClinicalTrials.gov，NCT02523976。
