Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial

Summary

Background

Our open-label, multicentre, randomised, phase 3 trial showed that sorafenib maintenance after haematopoietic stem-cell transplantation (HSCT) improved overall survival and reduced relapse for patients with FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukaemia undergoing allogeneic HSCT. Here, we present a post-hoc analysis on the 5-year follow-up data of this trial.

Methods

This phase 3 trial, done in seven hospitals in China, included patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic HSCT, who were aged 18–60 years, 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 after transplantation. Patients were randomly assigned (1:1) to receive sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30–60 days after transplantation. Randomisation was done with permuted blocks (block size four) via an interactive web-based system. Investigators and participants were not masked to group assignment. The primary endpoint was the 1-year cumulative incidence of relapse, which was reported previously. For this updated analysis, the 5-year endpoints were overall survival; cumulative incidence of relapse; non-relapse mortality; leukaemia-free survival; graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS); cumulative incidence of chronic GVHD; and late effects in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT02474290, and is complete.

Findings

Between June 20, 2015, and July 21, 2018, 202 patients were randomly assigned to sorafenib maintenance (n=100) or non-maintenance (n=102). Median follow-up was 60·4 months (IQR 16·7–73·3). Extended follow-up showed improved overall survival (72·0% [95% CI 62·1–79·7] vs 55·9% [45·7–64·9]; hazard ratio [HR] 0·55, 95% CI 0·34–0·88; p=0·011), leukaemia-free survival (70·0% [60·0–78·0] vs 49·0% [39·0–58·3]; 0·47, 0·30–0·73; p=0·0007), and GRFS (58·0% [47·7–67·0] vs 39·2% [29·8–48·5]; 0·56, 0·38–0·83; p=0·0030), lower cumulative incidence of relapse (15·0% [8·8–22·7] vs 36·3% [27·0–45·6]; 0·33, 0·18–0·60; p=0·0003), and no increase in non-relapse mortality (15·0% [8·8–22·7] vs 14·7% [8·6–22·3]; 0·79, 0·39–1·62; p=0·98) for patients in the sorafenib group compared with those in the control group. The 5-year cumulative incidence of chronic GVHD (54·0% [43·7–63·2] vs 51·0% [40·8–60·3]; 0·82, 0·56–1·19; p=0·73) did not differ significantly between the two groups and we did not find substantial differences in late effects between the two groups. There were no treatment-related deaths.

Interpretation

With extended follow-up, sorafenib maintenance after transplantation is associated with improved long-term survival and reduced relapse rates compared with non-maintenance, further supporting this strategy as a standard of care for patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic HSCT.

Funding

None.

Translation

For the Chinese translation of the abstract see Supplementary Materials section.