FLT3

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 44th 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.

References
  1. Brunner A. M. et al. Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission. Br J Haematol. 2016 Nov;175(3):496-504. DOI: 10.1111/bjh.14260. Epub 2016 Jul 19.
  2. Bazarbachi A. et al. Prophylactic or preemptive therapy with sorafenib after allogeneic hematopoietic cell transplantation improves overall survival of FLT3 AML patients. Oral abstract #OS2-1. 2018 European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, Lisbon, PT.