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Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy
Othman, J. Hwang, A. Brodermann, M. Abdallah, I. McCloskey, K. Gallipoli, P. Clarke, G. Dang, R. Vidler, J. Krishnamurthy, P.
Othman, J.
Hwang, A.
Brodermann, M.
Abdallah, I.
McCloskey, K.
Gallipoli, P.
Clarke, G.
Dang, R.
Vidler, J.
Krishnamurthy, P.
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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.
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, Mike
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, Mike
Zhao, R.
Belsham, E.
Murray, D.
Fowler, N.
O'Nions, J.
Khan, A.
Sellar, R.
Dillon, R.
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Date
2024
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Article
Citation
Othman J, Hwang A, Brodermann M, Abdallah I, McCloskey K, Gallipoli P, et al. Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy. Blood advances. 2024 Nov 12;8(21):5590-7. PubMed PMID: 39265176. Pubmed Central PMCID: PMC11541456 Jazz Pharmaceuticals. A.H. declares honoraria from Kite/Gilead. P.G. declares honoraria from Astellas. R. Dang declares meeting sponsorship from Jazz; and honoraria from AbbVie. J.V. declares meeting support from BeiGene, Janssen, and Jazz; and reports honoraria from AbbVie and AstraZeneca. P.K. declares honoraria from Jazz, Astellas, and Gilead; reports speakers bureau role with Astellas; and reports consultancy for Jazz and Gilead. A.-L.L. declares honoraria from Astella, AbbVie, Amgen, Kite, Novartis, Jazz, and Daiichi Sankyo; and speakers bureau role with Kite, Takeda, and Astellas. F.H. declares meeting sponsorship and honoraria from AbbVie. J.L. declares honoraria from Aptitude health. N.F. declares investigator meetings with Novartis and MEI Pharma. J. O’nions declares honoraria from Servier, Astellas, AbbVie, Jazz, and Janssen. Anjum Khan declares meeting sponsorship from Jazz, Medac, and Servier; speakers bureau role with AbbVie, Astellas, Jazz, and Servier; and consultancy/advisory board role for TC BioPharm, Incyte, Immedica, Novartis, Synairgen, and Takeda. R. Dillon declares research funding from AbbVie and Amgen; and consultancy with Astellas, Pfizer, Novartis, Jazz, BeiGene, Shattuck, and AvenCell. The remaining authors declare no competing financial interests. Epub 2024/09/12. eng.