Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
Zhejiang Provincial Key Lab of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, PR China.
Br J Haematol. 2024 Mar;204(3):861-870. doi: 10.1111/bjh.19182. Epub 2023 Nov 8.
Gilteritinib, a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor, was approved for relapsed/refractory (R/R) FLT3-mutated acute myeloid leukaemia (AML) patients but still showed limited efficacy. Here, we retrospectively analysed the efficacy and safety of different gilteritinib-based combination therapies (gilteritinib plus hypomethylating agent and venetoclax, G + HMA + VEN; gilteritinib plus HMA, G + HMA; gilteritinib plus venetoclax, G + VEN) in 33 R/R FLT3-mutated AML patients. The composite complete response (CRc) and modified CRc (mCRc) rates were 66.7% (12/18) and 88.9% (16/18) in patients received G + HMA + VEN, which was higher compared with that in G + HMA (CRc: 18.2%, 2/11; mCRc: 45.5%, 5/11) or G + VEN (CRc: 50.0%, 2/4; mCRc: 50.0%, 2/4). The median overall survival (OS) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 160.0 days and 231.0 days. The median duration of remission (DOR) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 82.0 days and 77.0 days. Four patients in the G + HMA + VEN group received alloHSCT after remission exhibited prolonged median DOR. The most common grade 3/4 adverse events were cytopenia, febrile neutropenia and pulmonary infection; there were no differences among the three groups. In conclusion, our data demonstrated promising response of G + HMA + VEN combination therapy in R/R FLT3-mutated AML, and it may be considered an effective therapy bridge to transplantation.
吉特替尼是一种有效的 FMS 样酪氨酸激酶 3(FLT3)抑制剂,已被批准用于治疗复发/难治性(R/R)FLT3 突变急性髓系白血病(AML)患者,但疗效仍有限。在这里,我们回顾性分析了 33 例 R/R FLT3 突变 AML 患者接受不同吉特替尼为基础的联合治疗(吉特替尼联合低甲基化剂和维奈托克,G+HMA+VEN;吉特替尼联合低甲基化剂,G+HMA;吉特替尼联合维奈托克,G+VEN)的疗效和安全性。接受 G+HMA+VEN 治疗的患者复合完全缓解(CRc)和改良 CRc(mCRc)率分别为 66.7%(12/18)和 88.9%(16/18),高于 G+HMA(CRc:18.2%,2/11;mCRc:45.5%,5/11)或 G+VEN(CRc:50.0%,2/4;mCRc:50.0%,2/4)。G+HMA+VEN、G+HMA 和 G+VEN 治疗的中位总生存期(OS)均未达到,分别为 160.0 天、231.0 天和 231.0 天。G+HMA+VEN、G+HMA 和 G+VEN 治疗的中位缓解持续时间(DOR)均未达到,分别为 82.0 天、77.0 天和 77.0 天。在缓解后接受异基因造血干细胞移植(alloHSCT)的 G+HMA+VEN 组有 4 例患者,DOR 中位数延长。最常见的 3/4 级不良事件是血细胞减少症、发热性中性粒细胞减少症和肺部感染;三组之间无差异。总之,我们的数据表明,G+HMA+VEN 联合治疗在 R/R FLT3 突变 AML 中具有良好的反应,可能是一种有效的移植治疗桥接。