Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3‐ITD: A multicenter phase 2 study

• DOI: 10.1111/joim.13738
• Publication Date: 2023-10-30T02:58:14Z
• Authors: Sijian Yu; Yu Zhang; Guopan Yu; Yu Wang; Ruoyang Shao; Xin Du; Na Xu; Dongjun Lin; Weihua Zhao; Xiong Zhang; Jie Xiao; Zhiqiang Sun; Lan Deng; Xinquan Liang; Hongyu Zhang; Ziwen Guo; Min Dai; Pengcheng Shi; Fen Huang; Zhiping Fan; Qiong Liu; Ren Lin; Xuejie Jiang; Li Xuan; Qifa Liu; Hua Jin
• Keywords: Azacitidine; Homoharringtonine; Venetoclax; Regimen; Clinical endpoint; Salvage therapy; Decitabine; Chemotherapy regimen

Abstract Background Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3 ‐internal tandem duplication ( FLT3‐ITD ) respond infrequently to salvage chemotherapy. Objective To investigate the efficacy of sorafenib plus triplet therapy venetoclax, azacitidine, homoharringtonine (VAH) as a in this population. Methods This multicenter, single‐arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML (aged 18–65 years) who were treated VAH. The primary endpoint composite complete remission (CRc) after two cycles. Secondary outcomes included overall response rate (ORR), safety, survival. Results Between July 9, 2020, March 19, 2022, 58 assessed for eligibility, 51 whom enrolled. median patient age 47 years (interquartile range [IQR] 31–57). CRc 76.5% ORR 82.4%. At follow‐up 17.7 months (IQR, 8.7–24.7), duration not reached (NR), survival 18.1 (95% confidence interval [CI], 11.8‐NR) event‐free 11.4 CI, 5.6‐NR). Grade 3 4 adverse events occurring ≥10% neutropenia (92.2%), thrombocytopenia 41 (80.4%), anemia 35 (68.6%), febrile 29 (56.9%), pneumonia 13 (25.5%), sepsis 6 (11.8%) patients. Treatment‐related death occurred (3.9%) Conclusions VAH regimen well tolerated highly active against . may be suitable therapeutic option population, but larger population trials are needed explored. Trial registration Clinical Trials Registry: NCT04424147