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De-escalation or discontinuation of tyrosine kinase inhibitor in patients with chronic myeloid leukemia: A multicentral, open-label, prospective trial in China.
Luo, Jie; Du, Xin; Lou, Jin; Wu, Jianwei; Ma, Liping; Huang, Jixian; Wang, Liangtuo; Tu, Chuanqing; Liu, Zelin; Chen, Liya; Tan, Yaxian; Luo, Dongmei; Liang, Hanyin; Yin, Changxin; Cao, Rui; Zhou, Xuan; Liu, Qifa; Liu, Xiaoli; Xu, Na.
Afiliação
  • Luo J; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Du X; Department of Hematology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen University School of Medicine Shenzhen China.
  • Lou J; Department of Hematology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen University School of Medicine Shenzhen China.
  • Wu J; Department of Hematology Jinan University Affiliated Jiangmen Hospital of Traditional Chinese Medicine Jiangmen Guangdong China.
  • Ma L; Department of Hematology, Sun Yat-sen Memorial Hospital Sun Yat-sen University Guangzhou China.
  • Huang J; Department of Hematology, Yuebei People's Hospital Shantou University Shaoguan Guangdong China.
  • Wang L; Department of Hematology People's hospital of Yang Jiang Yang Jiang Guangdong China.
  • Tu C; Department of Hematology, Bao' an District People Hospital The Second Affiliated Hospital of Shenzhen University Shenzhen China.
  • Liu Z; Department of Hematology Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital) Shenzhen China.
  • Chen L; Department of Medical Quality Management Nanfang Hospital Southern Medical University Guangzhou China.
  • Tan Y; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Luo D; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Liang H; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Yin C; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Cao R; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Zhou X; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Liu Q; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Liu X; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
  • Xu N; Department of Hematology Nanfang Hospital Southern Medical University Guangzhou China.
EJHaem ; 3(4): 1220-1230, 2022 Nov.
Article em En | MEDLINE | ID: mdl-36467815
Background: Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). Optimizing dose of tyrosine kinase inhibitors (TKIs) in the CML treatment maybe a new challenge to maintain effective and improving patients' quality of life. We hypothesized that administration of low-dose TKIs does not compromise major molecular response (MMR) in patients with CML who have a deep molecular response (DMR). Methods: We did an open-label, randomized trial at eight hospitals in China. Eligible CML-CP patients (aged 18-70 years) had shown continuous response to TKI more than 5 years and maintained MR4.5 (BCR-ABLIS ≤ 0.0032%) in recent 18 months. Patients were randomly assigned (1:1) to the TKI de-escalation group or the discontinuation group. Randomization was done with permuted blocks (block size four) and implemented through an interactive web-based randomization system. Recurrence was defined as the single sample with real time Quantitative PCR (RT-qPCR) measurement greater than 0.1% (MMR). The primary endpoint was 12-month MMR rate in patients who received de-escalation or discontinuation of TKIs. This study was registered at ClinicalTrials.gov (NCT04143087). Results: Around 125 patients were enrolled between October 23, 2019 and October 31, 2020, 62 patients received dose de-escalation of TKIs, while 63 patients in the discontinuation group. In the de-escalation group, molecular recurrence-free survival at 12 months was 88.32% (95% CI 79%-98%), whereas molecular recurrence-free survival in the discontinuation group at 12 months was 59.98% (95% CI 47-73). No progressions occurred at the data cut-off date. All 29 recurrence cases restart TKI treatment returned to MMR. Cytolytic NK cells as a proportion of lymphocyte cells were significantly increased from baseline after 6 months whether in the de-escalation or TKIs cessation group (P = 0.048, 0.001, respectively); compared with the relapsing patients, Tregs proportion was decreased (P = 0.003), and higher proportion of NK cells were found in non-relapsing patients whether in TKI de-escalation or discontinuation group (P = 0.011, 0.007, respectively). We also found that the de-escalation group showed better disease-specific HRQOL in regards to its impact on emotional functioning, fatigue, pain, and financial difficulties. Conclusion: With 88.32% MMR in 12-months follow-up after de-escalation TKIs' treatment, dose-halving could become a new treatment paradigm for CML patients who with DMR under continuing maintenance therapy with TKIs.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article