Difference between revisions of "Acute myeloid leukemia, FLT3-positive"
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+ | | style="background-color:#F0F0F0; width:15%" |[[File:MartinSchoen.jpg|frameless|upright=0.3|center]] | ||
+ | | style="width:35%" |<big>[[User:Marteens|Martin Schoen, MD, MPH]]<br>Chicago, IL</big> | ||
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<big>'''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 [[Acute myeloid leukemia|main AML page]] for other regimens.'''</big> | <big>'''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 [[Acute myeloid leukemia|main AML page]] for other regimens.'''</big> | ||
Revision as of 13:06, 10 May 2018
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Martin Schoen, MD, MPH Chicago, IL |
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
Cytarabine, Daunorubicin, Midostaurin
Cytarabine, Daunorubicin, and Midostaurin induction therapy for acute myeloid leukemia (AML)
First-line induction therapy, older patients or "unfit" patients
Cytarabine, Daunorubicin, Sorafenib
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Regimen
Study | Evidence |
---|---|
Uy et al. 2017 (CALGB 11001) | Phase II |
Chemotherapy
- Cytarabine (Cytosar) 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 BID on days 1 to 7
7-day course
Patients not achieving a hypoplastic marrow on day 14 received re-induction with 5+2 with sorafenib. Patients achieving a CR or CRi proceeded to 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
Cytarabine & 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 |
---|---|
Uy et al. 2017 (CALGB 11001) | Phase II |
Preceding treatment
Chemotherapy
- Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours once per day on days 1 to 5
- Sorafenib (Nexavar) 400 mg PO BID for 28 days
Two cycles
Treatment followed by sorafenib maintenance.
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
Midostaurin monotherapy
Midostaurin (Rydapt) maintenance therapy for acute myeloid leukemia (AML)
Sorafenib monotherapy
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Regimen
Study | Evidence |
---|---|
Uy et al. 2017 (CALGB 11001) | Phase II |
Preceding treatment
Chemotherapy
- Sorafenib (Nexavar) 400 mg PO BID
28-day cycle for up to 12 cycles
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
Relapsed or refractory, salvage therapy
Midostaurin monotherapy
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Variant #1
Study | Evidence | Comparator |
---|---|---|
Fischer et al. 2010 | Randomized Phase II | Midostaurin 100 mg BID |
Chemotherapy
- Midostaurin (Rydapt) 50 mg PO BID
Continued until progression
Variant #2
Study | Evidence | Comparator |
---|---|---|
Fischer et al. 2010 | Randomized Phase II | Midostaurin 50 mg BID |
Chemotherapy
- Midostaurin (Rydapt) 100 mg PO BID
Continued until progression
Variant #3
Study | Evidence |
---|---|
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
Azacitidine & Sorafenib
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Regimen
Study | Evidence |
---|---|
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 BID
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