Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission

We performed a retrospective study analysing the effect of sorafenib, an oral fms-Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post-transplant maintenance in adult patients with FLT3-internal tandem duplication (ITD)acute myeloid leukaemia (AML). We identified consecutive patients with FLT3-ITD AML diagnosed between 2008 and 2014 who received haematopoietic cell transplantation (HCT) in first complete remission (CR1). Post-HCT initiation of sorafenib (yes/no) was evaluated as a time-varying covariate in the overall survival/progression-free survival (OS/PFS) analysis and we performed a landmark analysis of controls alive without relapse at the median date of sorafenib initiation. We identified 26 sorafenib patients and 55 controls. Median follow-up was 272months post-HCT for sorafenib survivors, and 384months for controls (P=0021). The median time to initiating sorafenib was 68days post-HCT; 43 controls were alive without relapse at this cut-off. Sorafenib patients had improved 2-year OS in the d+68 landmark analysis (81% vs. 62%, P=0029). Sorafenib was associated with improved 2-year PFS (82% vs. 53%, P=00081) and lower 2-year cumulative incidence of relapse (82% vs. 377%, P=00077). In multivariate analysis, sorafenib significantly improved OS [Hazard ratio (HR) 026, P=0021] and PFS (HR 025, P=0016). There was no difference in 2-year non-relapse mortality (98% vs. 93%, P=082) or 1-year chronic graft-versus-host disease (555% vs. 372%, P=028). These findings suggest potential benefit of post-HCT sorafenib in FLT3-ITD AML, and support further evaluation of post-HCT FLT3 inhibition.