Difference between revisions of "Acute myeloid leukemia, FLT3-positive"

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# 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. [http://www.bloodjournal.org/content/121/23/4655.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674666/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23613521 PubMed]
 
# 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. [http://www.bloodjournal.org/content/121/23/4655.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674666/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23613521 PubMed]
  
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= Investigational agents =
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''These are drugs under study with at least some promising results for this disease.''
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* [[Gilteritinib (ASP2215)]]
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*
 
[[Category:Acute myeloid leukemia regimens]]
 
[[Category:Acute myeloid leukemia regimens]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Acute leukemias]]
 
[[Category:Acute leukemias]]

Revision as of 17:37, 12 May 2018


Page editor
MartinSchoen.jpg
 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
26 variants on this page


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

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

  1. 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

Two cycles

Treatment followed by sorafenib maintenance.

References

  1. 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

28-day cycle for up to 12 cycles

References

  1. 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

Continued until progression

Variant #2

Study Evidence Comparator
Fischer et al. 2010 Randomized Phase II Midostaurin 50 mg BID

Chemotherapy

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

28-day cycles

References

  1. 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
  2. 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

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

  1. 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.

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