Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial - 02/09/20

Doi : 10.1016/S1470-2045(20)30455-1

Li Xuan, MD ^a,^{^{†
Contributed equally}}, Yu Wang, ProfMD ^b,^{^{†
Contributed equally}}, Fen Huang, MD ^a,^{^{†
Contributed equally}}, Zhiping Fan, MD ^a, Yajing Xu, ProfMD ^c, Jing Sun, ProfMD ^a, Na Xu, MD ^a, Lan Deng, MD ^d, Xudong Li, MD ^e, Xinquan Liang, ProfMD ^f, Xiaodan Luo, MD ^g, Pengcheng Shi, MD ^a, Hui Liu, MD ^a, Zhixiang Wang, MD ^a, Ling Jiang, MD ^a, Chunzi Yu, MD ^b, Xuan Zhou, MD ^a, Ren Lin, MD ^a, Yan Chen, MD ^c, Sanfang Tu, MD ^d, Xiaojun Huang, ProfMD ^a,^b, Qifa Liu, ProfMD ^a,⁎

^a Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China

^b Department of Hematology, Peking University People’s Hospital, Beijing, China

^c Department of Hematology, Xiangya Hospital, Central South University, Changsha, China

^d Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China

^e Department of Hematology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

^f Department of Hematology, First People’s Hospital of Chenzhou, Chenzhou, China

^g Department of Hematology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

^* Correspondence to: Prof Qifa Liu, Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China Department of Hematology Nanfang Hospital Southern Medical University Guangzhou 510515 China

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.

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Vol 21 - N° 9

P. 1201-1212 - septembre 2020 Retour au numéro

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Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial - 02/09/20

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