Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Issue 9 (September 2020)

• Record Type: Journal Article
• Authors: Xuan, Li; Wang, Yu; Huang, Fen; Fan, Zhiping; Xu, Yajing; Sun, Jing; Xu, Na; Deng, Lan; Li, Xudong; Liang, Xinquan; Luo, Xiaodan; Shi, Pengcheng; Liu, Hui; Wang, Zhixiang; Jiang, Ling; Yu, Chunzi; Zhou, Xuan; Lin, Ren; Chen, Yan; Tu, Sanfang; Huang, Xiaojun; Liu, Qifa
• Is Part Of: Lancet oncology. Volume 21:Issue 9(2020)
• Page Start: 1201
• Page End: 1212
• Publication Date: 2020-09
• Subjects: Oncology -- Periodicals; Neoplasms -- Periodicals; Cancérologie -- Périodiques; Oncologie; Oncology; Periodicals; Electronic journals; 616.994005
• DOI: 10.1016/S1470-2045(20)30455-1
• Languages: English
• ISSNs: 1470-2045

Abstract

Summary: Background: Findings of retrospective studies suggest that sorafenib maintenance post-transplantation might reduce relapse in patients with FLT3 internal tandem duplication ( FLT3 -ITD) acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. We investigated the efficacy and tolerability of sorafenib maintenance post-transplantation in this population. Methods: We did an open-label, randomised phase 3 trial at seven hospitals in China. Eligible patients (aged 18–60 years) had FLT3 -ITD acute myeloid leukaemia, were undergoing allogeneic haematopoietic stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0–2, had composite complete remission before and after transplantation, and had haematopoietic recovery within 60 days post-transplantation. Patients were randomly assigned (1:1) to sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30–60 days post-transplantation. Randomisation was done with permuted blocks (block size four) and implemented through an interactive web-based randomisation system. The primary endpoint was the 1-year cumulative incidence of relapse in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02474290 ; the trial is complete. Findings: Between June 20, 2015, and July 21, 2018, 202 patients were enrolled and randomly assigned to sorafenib maintenance (n=100) or control (n=102). Median follow-up post-transplantation was 21·3 months (IQR 15·0–37·0). The 1-year cumulative incidence of relapse was 7·0% (95% CI 3·1–13·1) in the sorafenib group and 24·5% (16·6–33·2) in the control group (hazard ratio 0·25, 95% CI 0·11–0·57; p=0·0010). Within 210 days post-transplantation, the most common grade 3 and 4 adverse events were infections (25 [25%] of 100 patients in the sorafenib group vs 24 [24%] of 102 in the control group), acute graft-versus-host-disease (GVHD; 23 [23%] of 100 vs 21 [21%] of 102), chronic GVHD (18 [18%] of 99 vs 17 [17%] of 99), and haematological toxicity (15 [15%] of 100 vs seven [7%] of 102). There were no treatment-related deaths. Interpretation: Sorafenib maintenance post-transplantation can reduce relapse and is well tolerated in patients with FLT3 -ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. This strategy could be a suitable therapeutic option for patients with FLT3 -ITD acute myeloid leukaemia. Funding: None.