Nishiwaki Satoshi, Sugiura Isamu, Fujisawa Shin, Hatta Yoshihiro, Atsuta Yoshiko, Doki Noriko, Kurahashi Shingo, Ueda Yasunori, Dobashi Nobuaki, Maeda Tomoya, Matsumura Itaru, Tanaka Masatsugu, Kako Shinichi, Ichinohe Tatsuo, Fukuda Takahiro, Ohtake Shigeki, Ishikawa Yuichi, Miyazaki Yasushi, Sakaida Emiko, Maeda Yoshinobu, Yamauchi Takahiro, Kiyoi Hitoshi
Department of Advanced Medicine, Nagoya University Hospital, 65 Tsurumai-Cho Showa-Ku, Nagoya, 4668560, Japan.
Division of Hematology and Oncology, Toyohashi Municipal Hospital, Toyohashi, Japan.
Int J Hematol. 2025 Aug 27. doi: 10.1007/s12185-025-04058-1.
This study compared dasatinib and imatinib in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Using pooled data from three JALSG prospective trials (Ph + ALL202, Ph + ALL208, Ph + ALL213), we analyzed outcomes for 206 patients aged 15-64 years treated with dasatinib (n = 74) or imatinib (n = 132) in combination with chemotherapy. We applied propensity score matching (1:1) and inverse probability of treatment weighting to minimize selection bias and balance baseline characteristics. Dasatinib plus chemotherapy was associated with significantly higher complete molecular response rates after induction therapy compared with imatinib. In the propensity score-matched cohort (n = 68 patients per group), 3-year event-free survival (EFS) was significantly higher with dasatinib (73 vs. 49%, P = 0.01), as was 3-year overall survival (OS) (85 vs. 60%, P = 0.004). Multivariate analysis, incorporating allogeneic stem cell transplantation in first complete remission as a covariate, confirmed that dasatinib had an independent favorable prognostic impact on EFS (hazard ratio [HR], 0.54; P = 0.02) and OS (HR, 0.39; P = 0.003). Although the 3-year cumulative incidence of relapse tended to be lower with dasatinib (18 vs. 40%, P = 0.07), non-relapse mortality was comparable between groups (8.8 vs. 12%, P = 0.33). This analysis demonstrates improved survival with dasatinib-based therapy in adult Ph + ALL, informing tyrosine kinase inhibitor selection in treatment planning.
本研究比较了达沙替尼和伊马替尼在成人费城染色体阳性急性淋巴细胞白血病（Ph+ALL）中的疗效。利用日本成人白血病研究组（JALSG）三项前瞻性试验（Ph+ALL202、Ph+ALL208、Ph+ALL213）的汇总数据，我们分析了206例年龄在15至64岁之间接受达沙替尼（n = 74）或伊马替尼（n = 132）联合化疗的患者的预后。我们应用倾向评分匹配（1:1）和治疗权重逆概率法来尽量减少选择偏倚并平衡基线特征。与伊马替尼相比，达沙替尼联合化疗在诱导治疗后完全分子缓解率显著更高。在倾向评分匹配队列中（每组n = 68例患者），达沙替尼组的3年无事件生存率（EFS）显著更高（73%对49%，P = 0.01），3年总生存率（OS）也是如此（85%对60%，P = 0.004）。多变量分析将首次完全缓解时进行异基因干细胞移植作为一个协变量纳入，证实达沙替尼对EFS（风险比[HR]，0.54；P = 0.02）和OS（HR，0.39；P = 0.003）具有独立的有利预后影响。虽然达沙替尼组的3年累积复发率倾向于更低（18%对40%，P = 0.07），但两组间的非复发死亡率相当（8.8%对12%，P = 0.33）。该分析表明，在成人Ph+ALL中，基于达沙替尼的治疗可提高生存率，为治疗方案中酪氨酸激酶抑制剂的选择提供了依据。
