Acute myeloid leukemia, FLT3-positive
Page editor | |
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Martin Schoen, MD, MPH St. Louis, MO |
Note: these are biomarker-specific regimens for patients with FLT3 internal tandem duplicated (FLT3-ITD) or tyrosine kinase domain mutated (FLT3-TKD) AML, please see the main AML page for other regimens.
22 regimens on this page
27 variants on this page
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Upfront induction therapy, standard patients
7+3d & Midostaurin
Cytarabine, Daunorubicin, and Midostaurin induction therapy for acute myeloid leukemia (AML)
First-line induction therapy, older patients or "unfit" patients
7+3d & Sorafenib
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Regimen
Study | Evidence |
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Uy et al. 2017 (CALGB 11001) | Phase II |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m2)
- Daunorubicin (Cerubidine) 60 mg/m2 IV once per day on days 1 to 3
- Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 7
7-day course
Subsequent treatment
- Patients not achieving a hypoplastic marrow on day 14 received re-induction with 5+2 & sorafenib
- Patients achieving a CR or CRi: IDAC & sorafenib consolidation
References
- CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article contains verified protocol link to PMC article PubMed
Consolidation after upfront therapy
HiDAC & Midostaurin
Cytarabine & Midostaurin consolidation therapy for acute myeloid leukemia (AML)
IDAC & Sorafenib
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IDAC & Sorafenib: Intermediate Dose Ara-C (Cytarabine) & Sorafenib
Regimen
Study | Evidence |
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Uy et al. 2017 (CALGB 11001) | Phase II |
Preceding treatment
Chemotherapy
- Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours once per day on days 1 to 5
- Sorafenib (Nexavar) 400 mg PO twice per day for 28 days
Two cycles
Subsequent treatment
References
- CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article contains verified protocol link to PMC article PubMed
Maintenance after upfront therapy, including allogeneic HSCT
Midostaurin monotherapy
Midostaurin (Rydapt) maintenance therapy for acute myeloid leukemia (AML)
Sorafenib monotherapy
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Variant #1, 12 mos
Study | Evidence |
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Uy et al. 2017 (CALGB 11001) | Phase II |
Preceding treatment
Chemotherapy
- Sorafenib (Nexavar) 400 mg PO twice per day
28-day cycle for up to 12 cycles
Variant #2, 2 years
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buchert et al. 2018 (SORMAIN) | Phase III (E) | Placebo | Seems to have superior RFS |
Preceding treatment
- Allogeneic stem cell transplant
Chemotherapy
- Sorafenib (Nexavar) 200 mg PO twice per day, increasing to 400 mg PO twice per day
Continued for up to 2 years
References
- CALGB 11001: Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. link to original article contains verified protocol link to PMC article PubMed
- Abstract: Burchert A, Bug G, Finke J, Stelljes M, Rollig C, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner E, Kroeger N, Wolschke C, Schleuning M, Elmaagacli A, Götze KS, Schmid C, Jost E, Wolf D, Böhm A, Thiede C, Haferlach T, Bethge W, Harnisch S, Wittenberg M, Rospleszcz S, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK. Sorafenib As Maintenance Therapy Post Allogeneic Stem Cell Transplantation for FLT3-ITD Positive AML: Results from the Randomized, Double-Blind, Placebo-Controlled Multicentre Sormain Trial. Blood 2018, 132(Suppl 1), 661. Accessed February 13, 2019. link to abstract contains verified protocol Link to clinical trial registration
Relapsed or refractory, salvage therapy
Midostaurin monotherapy
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Variant #1
Study | Evidence | Comparator |
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Fischer et al. 2010 | Randomized Phase IIB (E) | Midostaurin 100 mg twice per day |
Chemotherapy
- Midostaurin (Rydapt) 50 mg PO twice per day
Continued indefinitely
Variant #2
Study | Evidence | Comparator |
---|---|---|
Fischer et al. 2010 | Randomized Phase IIB (E) | Midostaurin 50 mg twice per day |
Chemotherapy
- Midostaurin (Rydapt) 100 mg PO twice per day
Continued indefinitely
Variant #3
Study | Evidence |
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Stone et al. 2004 | Phase II |
Patients were required to have a FLT3 ITD or FLT3 p.D835Y mutation.
Chemotherapy
- Midostaurin (Rydapt) 75 mg PO TID
28-day cycles
References
- Stone RM, DeAngelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, Grandin W, Lebwohl D, Wang Y, Cohen P, Fox EA, Neuberg D, Clark J, Gilliland DG, Griffin JD. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005 Jan 1;105(1):54-60. Epub 2004 Sep 2. link to original article contains verified protocol PubMed
- Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. Epub 2010 Aug 23. link to original article link to PMC article contains verified protocolPubMed
Relapsed or refractory, further lines of therapy
Gilteritinib monotherapy
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Regimen
FDA-recommended dose |
Study | Evidence | Comparator | Efficacy |
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Perl et al. 2017 | Phase I/II | ||
ADMIRAL | Phase III (E) | Salvage Chemotherapy | Not reported |
Chemotherapy
- Gilteritinib (Xospata) 120 mg PO once per day
28-day cycles
References
- Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, Claxton D, Erba HP, Gill S, Goldberg S, Jurcic JG, Larson RA, Liu C, Ritchie E, Schiller G, Spira AI, Strickland SA, Tibes R, Ustun C, Wang ES, Stuart R, Röllig C, Neubauer A, Martinelli G, Bahceci E, Levis M. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017 Aug;18(8):1061-1075. Epub 2017 Jun 20. link to original article PubMed
- ADMIRAL Clinical Trial
Azacitidine & Sorafenib
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Regimen
Study | Evidence |
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Ravandi et al. 2013 | Phase II |
Chemotherapy
- Azacitidine (Vidaza) 75 mg/m2 SC or IV once per day on days 1 to 7
- Sorafenib (Nexavar) 400 mg PO twice per day
Supportive medications
- "All patients received antimicrobials, supportive care, and transfusions of blood products according to the institutional guidelines."
4 to 8 week cycles at treating physician's discretion
References
- Ravandi F, Alattar ML, Grunwald MR, Rudek MA, Rajkhowa T, Richie MA, Pierce S, Daver N, Garcia-Manero G, Faderl S, Nazha A, Konopleva M, Borthakur G, Burger J, Kadia T, Dellasala S, Andreeff M, Cortes J, Kantarjian H, Levis M. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013 Jun 6;121(23):4655-62. Epub 2013 Apr 23. link to original article contains verified protocol link to PMC article PubMed
Investigational agents
These are drugs under study with at least some promising results for this disease.