Journal Article

Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial

Huang, Fen, Wang, Yu, Luo, Xiaodan, Shi, Pengcheng, Xu, Na, Huang, Xiaojun, Jiang, Ling, Chen, Yan, Liang, Xinquan, Zhou, Xuan, Lin, Ren, Fan, Zhiping, Xuan, Li, Yu, Chunzi, Tu, Sanfang, Wang, Zhixiang, Li, Xudong, Xu, Yajing, Sun, Jing, Liu, Hui, Deng, Lan, Liu, Qifa

2020

Overview

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. 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. 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. 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. None.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Acute myeloid leukemia / Adolescent / Adult / Bone marrow / Chemotherapy / China - epidemiology / Creatinine / Disease-Free Survival / Drug-Related Side Effects and Adverse Reactions - drug therapy / Drug-Related Side Effects and Adverse Reactions - pathology / Female / fms-Like Tyrosine Kinase 3 - genetics / Graft vs Host Disease - epidemiology / Graft vs Host Disease - etiology / Graft vs Host Disease - genetics / Graft vs Host Disease - pathology / Graft-versus-host reaction / Hematology / Hematology, Oncology, and Palliative Medicine / Hematopoietic Stem Cell Transplantation - adverse effects / Hematopoietic stem cells / Humans / Immunoglobulins / Inhibitor drugs / Laboratories / Leukemia / Leukemia, Myeloid, Acute - drug therapy / Leukemia, Myeloid, Acute - epidemiology / Leukemia, Myeloid, Acute - genetics / Leukemia, Myeloid, Acute - pathology / Male / Medical prognosis / Middle Aged / Mutation / Neutrophils / Oncology / Patients / Protein Kinase Inhibitors / Remission / Remission Induction / Sorafenib - administration & dosage / Sorafenib - adverse effects / Stem cell transplantation / Tandem Repeat Sequences - genetics / Targeted cancer therapy / Toxicity / Transplantation, Homologous - adverse effects / Transplants & implants / Young Adult