酪氨酸激酶抑制剂治疗 3 个月内达到完全分子缓解的费城染色体阳性急性淋巴细胞白血病患者进展的预后因素。
Prognostic factors for progression in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in complete molecular response within 3 months of therapy with tyrosine kinase inhibitors.
机构信息
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
出版信息
Cancer. 2021 Aug 1;127(15):2648-2656. doi: 10.1002/cncr.33529. Epub 2021 Apr 1.
BACKGROUND
The achievement of a 3-month complete molecular response (CMR) is a major prognostic factor for survival in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, 25% of patients relapse during therapy with tyrosine kinase inhibitors (TKIs).
METHODS
The authors reviewed 204 patients with Ph-positive ALL who were treated between January 2001 and December 2018 using the combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus a TKI (imatinib, 44 patients [22%]; dasatinib, 88 patients [43%]; or ponatinib, 72 patients [35%]). Progression-free survival (PFS) was defined as the time from the start date of therapy to the date of relapse, death, or last follow-up. Overall survival (OS) was defined as the time from the start date of therapy to the date of death or last follow-up.
RESULTS
Overall, a 3-month CMR was observed in 57% of patients, including 32% of those who received imatinib, 52% of those who received dasatinib, and 74% of those who received ponatinib. The median follow-up was 74 months (imatinib, 180 months; dasatinib, 106 months; ponatinib, 43 months). Among 84 patients in 3-month CMR, 17 (20%) proceeded to undergo allogeneic stem cell transplantation (ASCT). The 5-year PFS and OS rates were 68% and 72%, respectively. By multivariate analysis, ponatinib therapy was the only significant favorable independent factor predicting for progression (P = .028; hazard ratio, 0.388; 95% CI, 0.166-0.904) and death (P = .042; hazard ratio, 0.379; 95% CI, 0.149-0.966). ASCT was not a prognostic factor for PFS and OS by univariate analysis.
CONCLUSIONS
In patients with Ph-positive ALL, ponatinib is superior to other types of TKIs in inducing and maintaining a CMR, thus preventing disease progression. ASCT does not improve outcome once a 3-month CMR is achieved.
背景
在费城染色体（Ph）阳性急性淋巴细胞白血病（ALL）患者中，达到 3 个月完全分子缓解（CMR）是生存的主要预后因素。然而，仍有 25%的患者在酪氨酸激酶抑制剂（TKI）治疗期间复发。
方法
作者回顾了 204 例 2001 年 1 月至 2018 年 12 月期间使用高剂量环磷酰胺（hyperfractionated cyclophosphamide）、长春新碱（vincristine）、多柔比星（doxorubicin）和地塞米松（dexamethasone）（hyper-CVAD）联合 TKI（伊马替尼 44 例[22%]；达沙替尼 88 例[43%]；或泊那替尼 72 例[35%]）治疗的 Ph 阳性 ALL 患者。无进展生存期（PFS）定义为从治疗开始日期到复发、死亡或末次随访的时间。总生存期（OS）定义为从治疗开始日期到死亡或末次随访的时间。
结果
总体而言，57%的患者达到 3 个月 CMR，其中伊马替尼组为 32%，达沙替尼组为 52%，泊那替尼组为 74%。中位随访时间为 74 个月（伊马替尼 180 个月；达沙替尼 106 个月；泊那替尼 43 个月）。在 84 例 3 个月 CMR 患者中，17 例（20%）进行了异基因造血干细胞移植（ASCT）。5 年 PFS 和 OS 率分别为 68%和 72%。多变量分析显示，泊那替尼治疗是唯一具有显著预后意义的独立有利因素，与进展（P =.028；风险比，0.388；95%CI，0.166-0.904）和死亡（P =.042；风险比，0.379；95%CI，0.149-0.966）相关。单变量分析显示 ASCT 不是 PFS 和 OS 的预后因素。
结论
在 Ph 阳性 ALL 患者中，泊那替尼在诱导和维持 CMR 方面优于其他类型的 TKI，从而预防疾病进展。一旦达到 3 个月 CMR，ASCT 并不能改善结局。
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