Faculty Collaboration Database

Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3. J Clin Oncol 2024 May 20;42(15):1766-1775

Date

03/12/2024

Pubmed ID

38471061

Pubmed Central ID

PMC11095884

DOI

10.1200/JCO.23.02474

Scopus ID

2-s2.0-85193456124 (requires institutional sign-in at Scopus site)   164 Citations

Abstract

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit.

METHODS: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS.

RESULTS: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575).

CONCLUSION: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Author List

Levis MJ, Hamadani M, Logan B, Jones RJ, Singh AK, Litzow M, Wingard JR, Papadopoulos EB, Perl AE, Soiffer RJ, Ustun C, Ueda Oshima M, Uy GL, Waller EK, Vasu S, Solh M, Mishra A, Muffly L, Kim HJ, Mikesch JH, Najima Y, Onozawa M, Thomson K, Nagler A, Wei AH, Marcucci G, Geller NL, Hasabou N, Delgado D, Rosales M, Hill J, Gill SC, Nuthethi R, King D, Wittsack H, Mendizabal A, Devine SM, Horowitz MM, Chen YB, BMT-CTN 1506/MORPHO Study Investigators

Authors

Mehdi Hamadani MBBS Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MS, MD Adjunct 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
Gene Duplication
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Maintenance Chemotherapy
Male
Middle Aged
Mutation
Neoplasm, Residual
Protein Kinase Inhibitors
Pyrazines
Tandem Repeat Sequences
Young Adult
fms-Like Tyrosine Kinase 3