Faculty Collaboration Database

Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML. Blood 2025 May 08;145(19):2138-2148

Date

01/08/2025

Pubmed ID

39775763

Pubmed Central ID

PMC12105721

DOI

10.1182/blood.2024025154

Scopus ID

2-s2.0-105000792090 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

BMT CTN (Blood and Marrow Transplant Clinical Trials Network) 1506 ("MORPHO") was a randomized study of gilteritinib compared with placebo as maintenance therapy after hematopoietic cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary end point was to determine the impact on survival of before and/or after HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD. We conducted a post hoc analysis of the data and found that the level of MRD detected with this approach correlated remarkably with RFS and relapse risk, and that MRD detectable at any level negatively affected RFS. In the placebo arm, 42.2% of participants with detectable FLT3-ITD MRD relapsed compared with 13.4% of those without detectable MRD. We found that 14.8% of participants had multiple FLT3-ITD clones detected as MRD and had worse survival irrespective of treatment arm. Finally, we examined the kinetics of FLT3-ITD clonal relapse or eradication and found that participants on the placebo arm with detectable MRD relapsed rapidly after HCT, often within a few weeks. MRD-positive participants on the gilteritinib arm relapsed either with FLT3 wild-type clones (assessed by capillary electrophoresis), after cessation of gilteritinib with persistent MRD, or on progression of multiclonal disease. These data demonstrate the potential of FLT3-ITD MRD to guide therapy with gilteritinib for this subtype of AML. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

Author List

Levis MJ, Hamadani M, Logan BR, Jones RJ, Singh AK, Litzow MR, Wingard JR, Papadopoulos EB, Perl AE, Soiffer RJ, Ustun C, Oshima MU, Uy GL, Waller EK, Vasu S, Solh M, Mishra A, Muffly LS, Kim HJ, Stelljes M, Najima Y, Onozawa M, Thomson K, Nagler A, Wei AH, Marcucci G, Chen C, Hasabou N, Rosales M, Hill J, Gill SC, Nuthethi R, King D, Mendizabal A, Devine SM, Horowitz MM, Chen YB

Authors

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Data Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aniline Compounds
Female
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Male
Middle Aged
Mutation
Neoplasm, Residual
Pyrazines
Young Adult
fms-Like Tyrosine Kinase 3