EBMT 2018 | Prophylactic or preemptive sorafenib therapy after allo-HCT improves survival of FLT3-mutated AML patients

Prophylactic or preemptive sorafenib therapy after allogeneic hematopoietic cell transplantation (allo-HCT) improves survival of fms-like tyrosine kinase 3 (FLT3) mutated acute myeloid leukemia (AML) patients according to a study presented by Ali Bazarbachi, from the American University of Beirut Medical Center, Beirut, LB, and colleagues at the 44^th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Lisbon, Portugal.

Previous studies have demonstrated a potential benefit for sorafenib maintenance post allo-HCT in FLT3-ITD AML.¹ In a retrospective registry-based analysis, Ali Bazarbachi and colleagues aimed to evaluate the safety and efficacy of sorafenib given as prophylactic or preemptive treatment in patients with FLT3 mutated AML post allo-HCT.²

Bazarbachi and colleagues identified from EBMT centers, 462 FLT3-mutated AML patients who underwent allo-HCT from either a matched-related, matched-unrelated or haploidentical donor between 2012–2015. In some patients, post-transplant sorafenib prophylactic (n = 19) or preemptive (n = 10) therapy was administered. Sorafenib treatment was initiated at a median of 55 days post-transplant (1–173) at a median dose of 800 (range, 200–800) mg daily for prophylaxis and a median dose of 800 (range, 400–800) mg daily for preemptive therapy.

With a follow-up time of 39 months (range 1–87) in surviving patients, it was found that sorafenib significantly reduced relapse incidence (RI; HR = 0.39, P =0.05), and improved leukemia-free survival (LFS; HR = 0.35, P = 0.013), overall survival (OS; HR = 0.36; P = 0.03) and graft versus host disease (GVHD) relapse-free survival (GRFS; HR= 0.44; P = 0.023).

Paired matched analysis of patients who were administered sorafenib (n = 26, median age at transplant = 50 years) and control (n = 26, median age at transplant = 49 years) who engrafted and with survival without relapse and without acute GVHD grade II–IV at least equal or superior to time to sorafenib initiation. Compared to the control (no sorafenib group), 2-year LFS (53.8% vs 79.1%, P = 0.02) and OS (61.5% vs 82.8%, P = 0.007) were significantly longer in the sorafenib group. Additionally, it was demonstrated that prophylactic or preemptive sorafenib significantly reduced RI (HR = 0.38, P = 0.046) and improved LFS (HR = 0.37, P = 0.024), and OS (HR = 0.32, P = 0.007) without affecting non-relapse mortality.

The speaker, Ali Bazarbachi, concluded by stating that “post-transplant prophylactic or preemptive sorafenib is a safe and effective therapy for patients with FLT3 mutated AML significantly improving LFS, OS, and GRFS”. He further added that the findings of their study indicate that sorafenib is a potent agent to prevent disease relapse and should be considered as part of the standard of care for post-alloHCT setting in FLT3 mutated AML patients.