Reference Detail

Ref Type

Journal Article

PMID

(38471061)

Authors

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

Title

Gilteritinib as Post-Transplant Maintenance for Acute Myeloid Leukemia With Internal Tandem Duplication Mutation of FLT3.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology			2024 Mar 12	JCO2302474	J Clin Oncol

URL

Abstract Text

Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with acute myeloid leukemia (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.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.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).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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Gilteritinib	Phase III	Actionable	In a Phase III trial, post-hematopoietic cell transplantation maintenance Xospata (gilteritinib) treatment improved relapse-free survival in patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation who had detectable minimal residual disease pre- or post-hematopoietic cell transplantation compared to placebo, but was not beneficial in patients without minimal residual disease (PMID: 38471061; NCT02997202).	38471061