Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy.
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ICR Authors
Authors
Othman, J
Hwang, A
Brodermann, M
Abdallah, I
McCloskey, K
Gallipoli, P
Clarke, G
Dang, R
Vidler, J
Krishnamurthy, P
Basheer, F
Latif, A-L
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
Hwang, A
Brodermann, M
Abdallah, I
McCloskey, K
Gallipoli, P
Clarke, G
Dang, R
Vidler, J
Krishnamurthy, P
Basheer, F
Latif, A-L
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
Document Type
Journal Article
Date
2024-11-12
Date Accepted
2024-07-22
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.
Citation
Blood advances, 2024, 8 (21), pp. 5590 - 5597
Source Title
Blood advances
Publisher
ELSEVIER
ISSN
2473-9529
eISSN
2473-9537
Collections
Research Team
Acute Leukaemia