10 targeted therapies for Acute Myeloid Leukemia(AML)

The main targeted therapies for Acute Myeloid Leukemia (AML) include:

FLT3 inhibitors

For AML with FLT3 mutations, such as midostaurin, gilteritinib, etc. These target the FLT3 tyrosine kinase.

Midostaurin^[1]

On April 28, 2017, the U.S. Food and Drug Administration approved midostaurin (RYDAPT, Novartis Pharmaceuticals Corp.) for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive (FLT3+), as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.

Approval Status	https://www.fda.gov/drugs/resources-information-approved-drugs/midostaurin
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/rydapt-midostaurin-1000156
Stage: clinical development	https://www.sciencedirect.com/topics/neuroscience/midostaurin

Approval Status	https://www.astellas.com/en/news/14271
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/xospata-gilteritinib-1000271
Stage: clinical development	https://www.sciencedirect.com/topics/medicine-and-dentistry/gilteritinib

Quizartinib^[3]

Tokyo, Munich and Basking Ridge, NJ – (June 18, 2019) – Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) announced today that the Ministry of Health, Labor and Welfare (MHLW) of Japan has approved VANFLYTA^® (quizartinib), an oral FLT3 inhibitor, for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML), as detected by an MHLW-approved test.

Approval Status	https://daiichisankyo.us/press-releases/-/article/364091/10393116
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/quizartinib-1000313
Stage: clinical development	https://www.sciencedirect.com/topics/medicine-and-dentistry/quizartinib

IDH1/2 inhibitors

For AML with IDH1/2 mutations, such as enasidenib, ivosidenib, etc. These target the mutant IDH1/2 enzymes.

Enasidenib^[4]

On August 1, 2017, the U.S. Food and Drug Administration granted regular approval to enasidenib (IDHIFA, Celgene Corp.) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.

Approval Status	https://www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-regular-approval-enasidenib-treatment-relapsed-or-refractory-aml
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/idhifa-enasidenib-1000160
Stage: clinical development	https://www.sciencedirect.com/topics/medicine-and-dentistry/enasidenib

Ivosidenib^[5]

On May 25, 2022, the Food and Drug Administration approved ivosidenib (Tibsovo, Servier Pharmaceuticals LLC) in combination with azacitidine (azacitidine for injection) for newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation, as detected by an FDA-approved test in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

Approval Status	https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-combination-azacitidine-newly-diagnosed-acute-myeloid-leukemia
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/tibsovo-ivosidenib-1000240
Stage: clinical development	https://www.sciencedirect.com/topics/medicine-and-dentistry/ivosidenib

Olutasidenib^[6]

On December 1, 2022, the Food and Drug Administration (FDA) approved olutasidenib (Rezlidhia) capsules for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.

Approval Status	https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olutasidenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-idh1-mutation
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/rezlidhia-olutasidenib-4000334
Stage: clinical development	https://www.sciencedirect.com/search?qs=Olutasidenib

BCL-2 inhibitors

Such as venetoclax. These target the BCL-2 protein and help restore apoptosis in cancer cells.

Approval Status	https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-venetoclax-combination-untreated-acute-myeloid-leukemia
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/venclexta-venetoclax-1000078
Stage: clinical development	https://www.sciencedirect.com/topics/medicine-and-dentistry/venetoclax

Antibody-drug conjugates

Such as gemtuzumab ozogamicin. These target surface proteins on AML blasts and deliver chemotherapy selectively to the cells.

Gemtuzumab ozogamicin^[8]

On September 1, 2017, the U.S. Food and Drug Administration approved gemtuzumab ozogamicin (Mylotarg, Pfizer Inc.) for the treatment of newly-diagnosed CD33-positive acute myeloid leukemia (AML) in adults and for treatment of relapsed or refractory CD33-positive AML in adults and in pediatric patients 2 years and older. Gemtuzumab ozogamicin may be used in combination with daunorubicin and cytarabine for adults with newly-diagnosed AML, or as a stand-alone treatment for certain adult and pediatric patients.

Approval Status	https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gemtuzumab-ozogamicin-cd33-positive-aml
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/mylotarg-gemtuzumab-1000186
Stage: clinical development	https://www.sciencedirect.com/topics/medicine-and-dentistry/gemtuzumab-ozogamicin

Hedgehog Inhibitors

Hedgehog pathway inhibitors target the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors.

Glasdegib^[9]

On November 21, 2018, the Food and Drug Administration approved glasdegib (DAURISMO, Pfizer Labs) in combination with low-dose cytarabine (LDAC), for newly-diagnosed acute myeloid leukemia (AML) in patients who are 75 years old or older or who have comorbidities that preclude intensive induction chemotherapy.

Approval Status	https://www.fda.gov/drugs/fda-approves-glasdegib-aml-adults-age-75-or-older-or-who-have-comorbidities
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/daurismo-glasdegib-1000274
Stage: clinical development	https://www.sciencedirect.com/topics/medicine-and-dentistry/glasdegib

FGFR 1 Inhibitor

Fibroblast growth factor receptor (FGFR) inhibitors are drugs used for treating cancer that originates in the skin or in tissues that line or cover internal organs (carcinoma).

Approval Status	https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pemigatinib-relapsed-or-refractory-myeloidlymphoid-neoplasms-fgfr1-rearrangement
Instructions for use:dosing, indications, interactions...etc.	https://reference.medscape.com/drug/pemazyre-pemigatinib-4000043
Stage: clinical development	https://www.sciencedirect.com/topics/medicine-and-dentistry/pemigatinib

Others

Others are being paired with therapeutic agents and Meds in the most promising clinical studies.

Multi-targeted kinase inhibitors

Such as midostaurin. These target multiple kinases involved in proliferation and survival of AML blasts.

MDM2 inhibitors

For AML with MDM2 amplification, such as idasanutlin. These target the MDM2-p53 interaction.

CD123 targeted therapies

Such as tagraxofusp. These target the IL-3 receptor CD123 which is overexpressed in AML blasts.

DOT1L inhibitors

Such as pinometostat. These target the DOT1L histone methyltransferase enzyme.

Hypomethylating agents

Such as azacitidine and decitabine. These target epigenetic changes and hypomethylate DNA to re-express tumor suppressor genes.

Chemotherapy

Cytarabine, anthracyclines, etoposide, etc. Conventional chemotherapy continues to play a role in AML treatment, often combined with targeted agents.