FLT3-inhibitor therapy for prevention and treatment of relapse after allogeneic hematopoietic cell transplantation

Abstract

The curative potential of allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) relies on the graft-versus-leukemia (GVL)-effect. Relapse after allo-HCT occurs in a considerable proportion of patients, and has a dismal prognosis with very limited curative potential, especially for patients with FLT-ITD-mutated AML. Since the first description of sorafenib for treatment of FLT3-ITD-mutated AML, several clinical trials have tried to determine the efficacy of FLT3 inhibitors for preventing and treating AML relapse after allo-HSCT, but many questions regarding differences among compounds and mechanisms of action remain unanswered. This review provides an overview on the established and evolving use of FLT3 inhibitors to prevent or treat relapse of AML in the context of allo-HCT, focusing on the recently discovered immunogenic potential of some FLT3 inhibitors and addressing the possible mechanisms of leukemia drug-escape.

Post‐stem cell transplant maintenance in FLT3mut acute myeloid leukemia – A retrospective analysis: Outcomes are improved with midostaurin but not with gilteritinib

“…The FMS‐like tyrosine kinase 3 ( FLT3 ) domain is the most mutated gene in acute myeloid leukemia (AML), with FLT3 internal tandem duplication (ITD) mutations conferring adverse outcomes [ 1 , 2 ]. Maintenance therapy after hematopoietic stem cell transplant (HSCT) may be essential, as FLT3 AML patients experience high rates of post‐HSCT relapse and mortality [ 3 ]. Terao et al.…”

Successful Pre- and Post-transplant Administration of Gilteritinib in a Patient with Relapsed and Refractory Acute Myeloid Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

“…In the ADMIRAL trial, despite the small numbers of patients receiving allo-SCT and subsequent post-transplant gilteritinib, the clinical impact of post-transplant gilteritinib was suggested to be beneficial ( 16 ). A clinical trial for maintenance treatment post-transplant is ongoing to clarify the clinical benefit of gilteritinib for patients who received allo-SCT(NCT02997202) ( 19 ).…”