Gilteritinib is approved for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with an FLT3-mutation (FLT3^mut+). However, the gilteritinib phase 3 ADMIRAL study (Perl et al NEJM 2019) was conducted prior to widespread adoption of either midostaurin as a component of standard intensive induction and consolidation or posttransplant FLT3 inhibitor maintenance. We performed a retrospective analysis using data from 11 US centers and where we identified 113 patients who received gilteritinib alone or as combination therapy for the treatment of R/R FLT3^mut+ AML. The composite complete remission (CR) rate (CRc, defined as CR + CR_i + CR with incomplete platelet recovery [CRp]) was 48.7% (n = 55). The CRc rate after treatment with gilteritinib in patients who were treated with only prior 7+3 and midostaurin with or without consolidation was 58% with a median survival of 7.8 months. Survival was longest in patients who obtained a CR, particularly a cMRD (clinical minimal or measurable residual disease) negative response; this remained significant after censoring at the time of stem cell transplant. The mitogen-activated protein kinase pathway activating mutations that are known for gilteritinib resistance (NRAS, KRAS, and PTPN11) had lower CRc (35% vs. 60.5%) and lower median overall survival than patients' whose leukemia did not express these mutations (4.9 months vs. 7.8 months) (HR 2.4; 95% CI 1. 5.4) p value <.01.

中文翻译：

---

Gilteritinib 在先前用 FLT3 抑制剂治疗的复发/难治性 FLT3 突变急性髓细胞白血病中的临床活性

Gilteritinib 被批准用于治疗具有 FLT3 突变 ( FLT3 ^mut+ ) 的复发/难治性 (R/R) 急性髓性白血病 (AML )。然而，gilteritinib 3 期 ADMIRAL 研究 (Perl 等 NEJM 2019) 是在广泛采用 midostaurin 作为标准强化诱导和巩固或移植后 FLT3 抑制剂维持的组成部分之前进行的。我们使用来自 11 个美国中心的数据进行了回顾性分析，其中我们确定了 113 名单独接受 gilteritinib 或作为治疗 R/R FLT3 ^mut+ AML 的联合疗法的患者。复合完全缓解 (CR) 率 (CRc，定义为 CR + CR _i  + CR 伴血小板恢复不完全 [CRp]) 为 48.7% ( n = 55)。在仅接受过 7+3 和 midostaurin 合并或未合并巩固治疗的患者中，gilteritinib 治疗后的 CRc 率为 58%，中位生存期为 7.8 个月。获得 CR，尤其是 cMRD（临床最小或可测量残留病）阴性反应的患者的存活时间最长；在干细胞移植时进行审查后，这仍然很重要。与未表达这些突变的白血病患者相比，丝裂原活化蛋白激酶通路激活突变已知导致 gilteritinib 耐药（NRAS、KRAS 和 PTPN11）具有较低的 CRc（35% 对 60.5%）和较低的中位总生存期。 4.9 个月与 7.8 个月）（HR 2.4；95% CI 1. 5.4）p值 <.01。