Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy
Othman, Jad Hwang, Angela Brodermann, Maximillian Abdallah, Islam McCloskey, Kayleigh Gallipoli, Paolo Clarke, Georgina Dang, Raymond Vidler, Jennifer Krishnamurthy, Pramila
Othman, Jad
Hwang, Angela
Brodermann, Maximillian
Abdallah, Islam
McCloskey, Kayleigh
Gallipoli, Paolo
Clarke, Georgina
Dang, Raymond
Vidler, Jennifer
Krishnamurthy, Pramila
Abstract
Gilteritinib is the current standard of care for relapsed or refractory fms related receptor tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or nonintensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and health care resource use is limited. Here, we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals. Median age was 61 years, and 36% had received ≥2 prior lines of therapy, including a FLT3 inhibitor in 41% and venetoclax in 24%. A median of 4 cycles of gilteritinib were administered, with 56% of patients requiring hospitalization in the first cycle (median, 10 days). Over half of patients required transfusion in each of the first 4 cycles. Complete remission (CR) was achieved in 21%, and CR with incomplete recovery (CRi) in a further 9%. Remission rates were lower for patients with FLT3-tyrosine kinase domain or adverse karyotype. Day-30 and day-60 mortality were 1% and 10.6%, respectively, and median overall survival was 9.5 months. On multivariable analysis, increasing age, KMT2A rearrangement, and complex karyotype were associated with worse survival whereas RUNX1 mutations were associated with improved survival. Twenty patients received gilteritinib as first salvage having progressed after first-line therapy with venetoclax, with CR/CRi achieved in 25% and median survival 4.5 months. Real-world results with gilteritinib mirror those seen in the clinical trials, but outcomes remain suboptimal, with more effective strategies needed.
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Date
2024-11-12
Type
Article
Other
Other
Subject
Oncology. Pathology., Haematology
Collections
Citation
Othman J, Hwang A, Brodermann M, Abdallah I, McCloskey K, Gallipoli P, Clarke G, Dang R, Vidler J, Krishnamurthy P, Basheer F, Latif AL, Palanicawandar R, Taylor T, Khan A, Campbell V, Hogan F, Kanellopoulos A, Fleming K, Collins A, Dalley C, Loke J, Marshall S, Taussig D, Munisamy S, Loizou E, Yassin H, Dennis M, Zhao R, Belsham E, Murray D, Fowler N, O'Nions J, Khan A, Sellar R, Dillon R. Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy. Blood Adv. 2024 Nov 12;8(21):5590-5597. doi: 10.1182/bloodadvances.2024014017.
Journal / Source Title
Blood advances
DOI
10.1182/bloodadvances.2024014017
PMID
39265176
Publisher
American Society of Hematology
Publisher’s URL
https://ashpublications.org/bloodadvances