背景:诊断为具有FLT3突变(FLT3+AML)的急性髓系白血病患者的预后较差。虽然在诱导治疗中添加FLT3抑制剂已被证明可以改善FLT3+AML的生存结果,诱导治疗期间使用的FLT3抑制剂和标准护理药物之间的相互作用和重叠毒性(例如,唑类抗真菌药,蒽环类药物)和后勤障碍使其使用复杂化。为了避免这些担忧,我们的机构选择将midostaurin的开始时间推迟到诱导治疗完成后.然而,据我们所知,目前还没有发表证实该策略在现实世界中使用FLT3抑制剂的有效性的研究.
方法:我们执行了一个中心,倾向得分匹配,回顾性队列研究描述了我们使用FLT3抑制剂治疗FLT3+AML策略的有效性和安全性.主要结局是中位无事件生存期(EFS),次要终点包括中位总生存期(OS),总反应率(ORR),30天死亡率,中性粒细胞减少症的持续时间,血小板减少症的持续时间,合并周期延迟,记录在案的感染,和所有原因的医院再入院。
结果:共有83例FLT3+AML患者接受了强化诱导治疗,其中48人倾向评分匹配并分析。在诱导治疗后接受FLT3抑制剂的患者和历史对照组之间的基线特征相似。EFS中位数没有显著差异,但在FLT3抑制剂队列和历史对照之间比较有利(未达到vs8个月,p=0.343),两个队列的18个月EFS分别为54%和43%,分别。同样,中位OS无显著差异(未达到vs28.7个月,p=0.752),ORR(79.2%vs79.2%),或组间的安全结果。
结论:与历史对照相比,在随访时间较长,样本量较大的真实世界患者队列中,在诱导后强化化疗中加入FLT3抑制剂可能会改善EFS或OS.在诱导中省略midostaurin,从而可以使用唑类抗真菌剂,并且蒽环类药物剂量的增加可能导致两组的高缓解率。
BACKGROUND: Patients diagnosed with acute myeloid leukemia with a FLT3 mutation (FLT3+ AML) have historically had poor outcomes. While the addition of the FLT3 inhibitors to induction therapy has been shown to improve survival outcomes in FLT3+ AML, interactions and overlapping toxicities between FLT3 inhibitors and standard of care medications used during induction therapy (e.g. azole antifungals, anthracyclines) and logistical barriers have complicated their use. To avoid these concerns, our institution has opted to defer initiation of
midostaurin until after completion of induction therapy. However, to our knowledge no
study confirming the effectiveness of this strategy for real world FLT3 inhibitor use has been published.
METHODS: We performed a single center, propensity-score matched, retrospective cohort
study characterizing efficacy and safety of our strategy for use of FLT3 inhibitors in the treatment of FLT3+ AML. The primary outcome was median event-free survival (EFS), while secondary endpoints included median overall survival (OS), overall response rate (ORR), 30-day mortality, duration of neutropenia, duration of thrombocytopenia, consolidation cycle delays, documented infections, and all-cause hospital readmission.
RESULTS: A total of 83 FLT3+ AML patients treated with intensive induction therapy were included in the
study, of whom 48 were propensity-score matched and analyzed. Baseline characteristics were similar between the patients who received a FLT3 inhibitor after induction therapy and the historical control arm. Median EFS was not significantly different but compared favorably between the FLT3 inhibitor cohort and historical controls (not reached vs 8 months, p = 0.343) with 18-month EFS of 54% and 43% for the two cohorts, respectively. Similarly, no significant differences were noted with regard to median OS (not reached vs 28.7 months, p = 0.752), ORR (79.2% vs 79.2%), or safety outcomes between groups.
CONCLUSIONS: Compared to historical controls, addition of a FLT3 inhibitor to intensive chemotherapy post-induction may improve EFS or OS in a real world patient cohort with longer follow-up and a larger sample size. The omission of
midostaurin in induction allowed for the use of an azole antifungal and the intensification of anthracycline dose may have contributed to high remission rates in both groups.