METHODS: A total of 266 AML patients (127 newly diagnosed [ND] and 139 refractory/relapsed [R/R]) receiving VEN-based regimens were enrolled in this study. A retrospective analysis was performed, and the treatment responses and overall survival (OS) of FLT3mut and FLT3wt patients were compared. Logistic regression and Cox proportional hazards model were applied to examine the clinical and genetic predictors of outcomes.
RESULTS: With a median of two cycles of VEN-based therapy, for the ND AML cohort, the FLT3mut group had a comparable composite complete remission (CRc) rate with the FLT3wt group (79.3% vs. 61.2%, p = 0.072). For the R/R AML cohort, the FLT3mut group exhibited a lower CRc rate than the FLT3wt group. With a median follow-up of 8.6 months (95% confidence interval [CI], 8.0-10), the median OS observed in the FLT3mut and FLT3wt groups for both cohorts were close (14.0 vs. 19.9 months, p = 0.356; 10.0 vs. 11.9 months, p = 0.680). For the ND AML cohort, in FLT3mut patients, MRD-positive and RNA-splicing mutation predicted inferior survival (hazard ratio [HR], 10.3; 95% CI: 2.0-53.8; p = 0.006; HR 11.3; 95% CI: 1.2-109.3; p = 0.036, respectively). For the R/R AML cohort, in FLT3mut patients, adverse ELN risk was associated with an inferior response (odds ratio [OR], 0.2; 95% CI: 0.1-0.8; p = 0.025), whereas NPM1 co-mutation was associated with a superior response (57.1%; OR, 6.7; 95% CI: 1.5-30.1; p = 0.014). CR/CRi predicted a better survival (HR 0.2; 95% CI: 0.1-0.8; p = 0.029), while DNMT3A mutation predicted an inferior survival (HR, 4.6; 95% CI: 1.4-14.9; p = 0.011).
CONCLUSIONS: FLT3 mutations may influence response to VEN-based therapy in R/R AML patients but not in ND AML patients. Furthermore, clinical and genetic characteristics could predict outcomes of FLT3mut patients receiving VEN-based therapy.
方法:本研究共纳入266例AML患者(127例新诊断[ND]和139例难治性/复发性[R/R])接受基于VEN的方案。进行了回顾性分析,比较FLT3mut和FLT3wt患者的治疗反应和总生存期(OS)。应用Logistic回归和Cox比例风险模型来检查结果的临床和遗传预测因子。
结果:基于VEN的治疗的中位数为两个周期,对于NDAML队列,FLT3mut组的复合完全缓解率(CRc)与FLT3wt组相当(79.3%vs.61.2%,p=0.072)。对于R/RAML队列,FLT3mut组的CRc率低于FLT3wt组。中位随访时间为8.6个月(95%置信区间[CI],8.0-10),在两个队列的FLT3mut和FLT3wt组中观察到的中位OS接近(14.0vs.19.9个月,p=0.356;10.0与11.9个月,p=0.680)。对于NDAML队列,在FLT3mut患者中,MRD阳性和RNA剪接突变预测生存率较低(风险比[HR],10.3;95%CI:2.0-53.8;p=0.006;HR11.3;95%CI:1.2-109.3;p=0.036)。对于R/RAML队列,在FLT3mut患者中,不良ELN风险与不良反应相关(比值比[OR],0.2;95%CI:0.1-0.8;p=0.025),而NPM1共突变与优越的反应相关(57.1%;OR,6.7;95%CI:1.5-30.1;p=0.014)。CR/CRi预测更好的生存期(HR0.2;95%CI:0.1-0.8;p=0.029),而DNMT3A突变预测存活率较低(HR,4.6;95%CI:1.4-14.9;p=0.011)。
结论:FLT3突变可能影响R/RAML患者对基于VEN的治疗的反应,但不影响NDAML患者。此外,临床和遗传特征可以预测FLT3mut患者接受VEN治疗的结局.