Contemporary outcomes in IDH-mutated acute myeloid leukemia: The impact of co-occurring NPM1 mutations and venetoclax-based treatment
Contemporary outcomes in IDH-mutated acute myeloid leukemia: The impact of co-occurring NPM1 mutations and venetoclax-based treatment
复制标题
DOI：
10.1002/ajh.26694
复制
发表时间：
2022-09-15
影响因子：
12.8
通讯作者：
DiNardo, Courtney D.
中科院分区：
文献类型：
--
作者：
Lachowiez, Curtis A.;Reville, Patrick K.;DiNardo, Courtney D.
异柠檬酸脱氢酶 1 或 2（IDH1 或 IDH2）突变在新诊断 (ND) 急性髓系白血病 (AML) 中频繁发生，通常与 NPM1 突变同时发生，这可能会影响治疗结果。使用 Venetoclax 治疗的 IDH 突变 AML 的详细分析以及同时发生的 NPM1 突变的影响仍不清楚。这项回顾性单中心队列研究评估了 IDH1 或 IDH2 突变 AML 患者的临床和分子人口统计学、反应和生存以及同时发生的 NPM1 突变的影响。纳入了 556 名 IDH1、IDH2 和/或 NPM1 突变的 AML 患者。与 IDH2(mut) (N = 229) 或 IDHwt/NPM1(mut) AML (N = 208) 患者相比，IDH1(mut) AML (N = 119) 患者更有可能出现年龄较大、sAML、ELN 不良风险疾病和不良风险细胞遗传学。在多变量分析中，与 IDH1(mut) AML 相比，IDH2(mut)（HR 0.61 [95%CI: 0.43-0.88]，p 值：0.007）或 IDHwt/NPM1(mut)（HR 0.65 [95% CI: 0.45-0.94]，p 值：0.024）AML 患者的死亡风险降低。基于 Venetoclax 的低强度治疗方案部分消除了 IDH1(mut) 的有害影响，并且在 IDH1(mut)/NPM1(wt)、IDH2(mut)/NPM1(wt) 和 IDHwt/NPM1(mut) AML 之间观察到相似的 OS。关于 IDHmut/NPM1(mut) 病例的影响，与 IDH2(mut)/NPM1(wt) AML 相比，IC 改善了 IDH2(mut)/NPM1(mut) 的生存率（HR：0.54 [95% CI：0.2644-1.082]，p 值：0.077），而基于维奈托克的治疗则改善了 IDH1(mut)/NPM1(mut) 的生存率IDH1(mut)/NPM1(wt) AML（HR：0.094 [95% CI：0.01-0.74]，p 值：0.0056）。在 IDH1(mut) 与 IDH2(mut) 或 NPM1(mut) AML 中观察到不同的结果，这些结果受到同时发生的 NPM1 突变的影响，并通过基于维奈托克的治疗部分消除。鉴于 IDH1(mut) AML 的不同生物学和生存率，在该亚组中仍需要结合 IDH 抑制剂等分子靶向治疗进行研究。
Isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations occur frequently in newly diagnosed (ND) acute myeloid leukemia (AML) often with co-occurring NPM1 mutations, which may influence treatment outcomes. Detailed analysis of IDH-mutated AML treated with venetoclax and influence of co-occurring NPM1 mutations remains unclear. This retrospective single-center cohort study evaluated clinical and molecular demographics,response and survival, and impact of co-occurring NPM1 mutations in patients with IDH1 or IDH2-mutated AML. 556 patients with IDH1, IDH2, and/or NPM1 mutated AML were included. Patients with IDH1(mut) AML (N = 119) were more likely to have older age, sAML, ELN-adverse risk disease, and adverse-risk cytogenetics compared to those with IDH2(mut) (N = 229) or IDHwt/NPM1(mut) AML (N = 208). In multivariate analysis, patients with IDH2(mut) (HR 0.61 [95%CI: 0.43-0.88], p value: .007) or IDHwt/NPM1(mut) (HR 0.65 [95% CI: 0.45-0.94], p value: .024) AML had a decreased risk of death versus IDH1(mut) AML. Venetoclax-based lower-intensity regimens partially abrogated the detrimental effect of IDH1(mut) with similar OS observed between IDH1(mut)/NPM1(wt), IDH2(mut)/NPM1(wt), and IDHwt/NPM1(mut) AML. With regards to the influence of IDHmut/NPM1(mut) cases, IC improved survival in IDH2(mut)/NPM1(mut) versus IDH2(mut)/NPM1(wt) AML (HR: 0.54 [95% CI: 0.2644-1.082], p value: .077), while venetoclax-based therapy improved survival in IDH1(mut)/NPM1(mut) versus IDH1(mut)/NPM1(wt) AML (HR: 0.094 [95% CI: 0.01-0.74], p value: .0056). Differing outcomes were observed in IDH1(mut) versus IDH2(mut) or NPM1(mut) AML which were influenced by co-occurring NPM1 mutations and partially abrogated with venetoclax-based therapy. Given the differing biology and survival in IDH1(mut) AML, investigations incorporating molecularly targeted therapies such as IDH inhibitors remain warranted in this subgroup.