Maintenance therapy with the FMS-like tyrosine kinase 3 inhibitor gilteritinib in patients with FMS-like tyrosine kinase 3-internal tandem duplication acute myeloid leukemia: A phase 2 study.

No Thumbnail Available

All Authors

Gyan, E.
Minden, MD.
Kubo, K.
Rambaldi, A.
Juliusson, G.
Jadersten, M.
Kelly, RJ.
Szerafin, L.
He, W.
Gill, SC.

LTHT Author

Kelly, Richard

LTHT Department

Oncology
Haematology

Non Medic

Publication Date

2025

Item Type

Journal Article
Clinical Trial
Randomised Controlled Trial
Multicenter Study

Language

Subject

Subject Headings

Abstract

BACKGROUND: The GOSSAMER phase 2 study assessed the FMS-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib as maintenance therapy in patients with FLT3-internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML) in first complete remission without previous hematopoietic stem cell transplantation (HSCT). METHODS: Patients had to be within 2 months of their last consolidation cycle and have completed the recommended number of cycles per local practice. FLT3 inhibitors were allowed only during induction and/or consolidation. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS), event-free survival, and measurable residual disease (MRD). RESULTS: In total, 98 patients were randomized (gilteritinib, n = 63; placebo, n = 35). RFS was not significantly different between the arms (hazard ratio, 0.74; 95% confidence interval, 0.41-1.34; p = .16). RFS rates for the gilteritinib and placebo arms were 68.5% and 55.3% at 1 year, 51.8% and 44.9% at 2 years, and 41.2% and 40.8% at 3 years, respectively. OS was not significantly different between the arms but may have been affected by subsequent AML therapies after discontinuation. In patients who received subsequent therapy (gilteritinib, 46.8%; placebo, 60.0%), a higher percentage of placebo-treated (57.1%) versus gilteritinib-treated patients (27.6%) underwent HSCT. At the end of treatment, 96.4% of gilteritinib-treated and 85.7% of placebo-treated patients had undetectable MRD. Relapsed placebo-treated (86.7%) versus gilteritinib-treated patients (34.8%) had a greater FLT3 mutational burden. No new significant safety concerns were noted. CONCLUSIONS: The primary end point was not achieved; however, an observed trend toward potential benefit was noted in patients with FLT3-ITD AML who had not undergone prior HSCT.

Journal

Cancer