3个月的完全分子反应(CMR)的实现是费城染色体(Ph)阳性急性淋巴细胞白血病(ALL)患者生存的主要预后因素。然而,25%的患者在使用酪氨酸激酶抑制剂(TKIs)治疗期间复发。
作者回顾了2001年1月至2018年12月期间使用超CVAD(超分割环磷酰胺,长春新碱,阿霉素,和地塞米松)加TKI(伊马替尼,44例患者[22%];达沙替尼,88例患者[43%];或普纳替尼,72例患者[35%])。无进展生存期(PFS)定义为从治疗开始日期到复发日期的时间,死亡,或最后的后续行动。总生存期(OS)定义为从治疗开始日期到死亡或最后随访日期的时间。
总的来说,在57%的患者中观察到3个月的CMR,包括32%接受伊马替尼治疗的患者,接受达沙替尼的人中有52%,和74%接受普纳替尼的患者。中位随访时间为74个月(伊马替尼,180个月;达沙替尼,106个月;普纳替尼,43个月)。在3个月CMR的84名患者中,17人(20%)继续进行异基因干细胞移植(ASCT)。5年PFS和OS率分别为68%和72%,分别。通过多变量分析,帕纳替尼治疗是预测进展的唯一显著有利的独立因素(P=.028;风险比,0.388;95%CI,0.166-0.904)和死亡(P=0.042;风险比,0.379;95%CI,0.149-0.966)。通过单因素分析,ASCT不是PFS和OS的预后因素。
在Ph阳性ALL患者中,普纳替尼在诱导和维持CMR方面优于其他类型的TKIs,从而防止疾病进展。一旦达到3个月的CMR,ASCT不会改善结果。
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).
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.
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.
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.