Dr. Ahmed Acute Myeloid Leukemia (AML) is a type of cancer that affects the bone marrow and blood cells. It occurs due to abnormal myeloid cells which produce RBCs & WBCs.
This type of cancer is more common in adults over 65 years of age. The chances of survival mainly depend on early diagnosis and proper treatment.
Here is a list of effective AML medications.
Class | Medicine |
| Nucleoside metabolic inhibitors |
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| Anthracycline antibiotics |
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| Purine analogs |
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| Nucleoside analogs | Cytarabine |
| Alkylating agents | Cyclophosphamide |
| Monoclonal antibodies | Gemtuzumab |
| Protein kinase inhibitors | Midostaurin |
| Tyrosine kinase inhibitors | Gilteritinib |
| IDH inhibitors (1 & 2) |
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| BCL 2 inhibitors | Venetoclax |
| Hedgehog pathway inhibitors | Glasdegib |
Azacitidine for AML |
| Generic name: Azacitidine Trade name: Onureg, Vidaza Date of approval: September 1, 2020 [ref] Company name: Reddy’s Laboratories Uses: For the therapy of Acute Myeloid Leukemia, Refractory Anemia, and Chronic Myelomonocytic Leukemia. MOA: A chemical analog of the cytosine nucleoside found in DNA and RNA is azacitidine (5-azacytidine). Azacitidine has the potential to cause cytotoxicity by incorporation into RNA and DNA at high dosages and antineoplastic action by inhibiting DNA methyltransferase at low concentrations. DNA becomes hypomethylated as a result of covalent attachment to DNA methyltransferase, which also stops DNA synthesis. As a ribonucleoside, azacitidine incorporates more readily into RNA than DNA. As a result of the incorporation into RNA, polyribosomes disassemble, transfer RNA’s methylation and acceptor function are compromised, protein synthesis is inhibited, and the cell dies. Major contraindications:PO
SC or IV
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Cytarabine for AML |
| Generic name: Cytarabine Trade name: Cytosar, Vyxeos Company name: Pfizer Inc. Date of approval: August 3, 2017 [ref] MOA: Direct DNA damage and integration into DNA are how cytarabine works. It appears to function by inhibiting DNA polymerase, while the exact mechanism of action is yet unclear. There has also been evidence of a small but considerable incorporation of cytarabine into both DNA and RNA. Uses: Acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia are conditions for which Cytarabine is occasionally used. Major contraindications:Hypersensitivity, ongoing meningeal infection |
Daunorubicin for AML |
| Generic name: Daunorubicin Trade name: Cerubidine Date of approval: December 19, 1979 [ref] Company name: Hikma Pharmaceuticals Uses: For the therapy of acute myeloid leukemia, and acute lymphocytic leukemia in children. MOA: This anthracycline antibiotic, daunorubicin harms DNA by intercalating between base pairs, which causes the helix to uncoil and ultimately prevents DNA synthesis and DNA-dependent RNA synthesis. Major contraindications:
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Idarubicin for AML |
| Generic name: Idarubicin Trade name: Idamycin Date of approval: September 1990 [ref] Company name: Pfizer Oncology Uses: For the therapy of acute myeloid leukemia. MOA: Idarubicin intercalates into DNA and disrupts the function of topoisomerase II, preventing the replication of DNA, transcription of RNA, and synthesis of proteins. Idarubicin penetrates cell membranes more effectively than other anthracycline antibiotic compounds because of its high lipophilicity. Major contraindications:
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Fludarabine for AML |
| Generic name: Fludarabine Trade name: Fludara Company name: Bayer HealthCare Pharmaceuticals Date of approval: April 18, 1991 [ref] MOA: Fludarabine phosphate undergoes quick dephosphorylation to become 2-fluoro-ara-A, which is subsequently intracellularly phosphorylated by deoxycytidine kinase to become the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to prevent DNA synthesis by impeding DNA primase, ribonucleotide reductase, and DNA polymerase alpha. This drug’s mode of action is not fully understood and could have many components. Uses: In order to treat chronic lymphocytic leukemia (CLL), fludarabine is typically utilized. Acute myeloid leukemia, hairy cell leukemia, low-grade non-Hodgkin lymphoma (NHL), and mycosis fungoides, a skin-related malignancy, may also be treated with it in clinical studies. Major contraindications:
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Cyclophosphamide for AML |
| Generic name: Cyclophosphamide Trade name: Procytox, Cytoxan Company name: Baxter Oncology Date of approval: August 17, 1999 [ref] MOA: Cyclophosphamide is a nitrogen mustard-type alkylating agent. Cross-linking of DNA and RNA strands and the suppression of protein synthesis are the principal causes of its cytotoxic effects. Uses: It is used for the therapy of multiple myeloma, acute myelogenous and monocytic leukemia [fda indications], mycosis fungoides, malignant lymphomas, retinoblastoma, neuroblastoma, and adenocarcinoma of the ovary. Major contraindications:
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Cladribine Decitabine For AML |
| Generic name: Cladribine Trade name: Litak, Mavenclad Date of approval: Not available for AML Company name: Merck Uses: For the therapy of Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Acute Myeloid Leukemia. MOA: By incorporating themselves into DNA and by inhibiting enzymes involved in DNA metabolism, such as DNA polymerase and ribonucleotide reductase, cladribine-phosphates prevent the synthesis and repair of DNA. DNA strand breakage and ultimately cell death result from this. Major contraindications:Hypersensitivity |
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Decitabine for AML |
| Generic name: Decitabine Trade name: Dacogen, Inqovi 5 Tablet Pack Date of approval: Not available for AML Company name: Genentech Inc Uses: As a first-line treatment for elderly AML patients MOA: Causes hypomethylation of DNA and cellular differentiation or death by inhibiting DNA methyltransferase Major contraindications:Hypersensitivity |
Gemtuzumab for AML |
| Generic name: Gemtuzumab Trade name: Mylotarg Date of approval: September 1, 2017 [ref] Company name: Pfizer Uses: It is recommended for the treatment of individuals with CD33-positive acute myeloid leukemia in the first relapse who are 60 or over in age and who are not deemed suitable for other cytotoxic chemotherapy. Indicated for the treatment of individuals with CD33-positive AML who are 2 years of age or older and have had a recurrence or have not responded to initial therapy (refractory). MOA: Mylotarg works by targeting the CD33 antigen that hematopoietic cells express. A complex that is internalized is created when the anti-CD33 antibody component of Mylotarg binds to the CD33 antigen. The calicheamicin derivative is internalized and then released inside the myeloid cell’s lysosomes. Through the production of a p-benzene diradical, the calicheamicin derivative that has been produced attaches to DNA in the minor groove and causes site-specific DNA double-strand breaks. Ultimately, cell death is brought about. Major contraindications:Hypersensitivity to the gemtuzumab active ingredient, any of its ingredients, or any of the excipients |
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Midostaurin for AML |
| Generic name: Midostaurin Trade name: Rydapt Date of approval: April 28, 2017 [ref] Company name: Novartis Uses: For use in adult patients with FLT3 mutation-positive high-risk acute myeloid leukemia (AML), systemic mastocytosis with associated hematological neoplasm (SM-AHN), and severe systemic mastocytosis (ASM). MOA: It effectively blocks a number of receptor tyrosine kinases. A number of tyrosine kinases, including protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR, and WT and/or mutant FLT3 tyrosine kinases are inhibited by midostaurin and its two main active metabolites, CGP62221 and CGP52421. Apoptosis is induced in target leukemia cells that express the target receptors as well as in mast cells when FLT3 receptor signaling cascades are inhibited. This is in addition to the antiproliferative effect against various cancer cell lines. Major contraindications:Hypersensitivity responses have included angioedema, dyspnea, flushing, and anaphylactic shock |
Gilteritinib for AML |
| Generic name: Gilteritinib Trade name: Xospata Date of approval: November 28, 2018 [ref] Company name: Astellas Pharma Uses: Adult patients with acute myeloid leukemia who have relapsed or are resistant to therapy and have an FLT3 mutation identified by an FDA-approved test are eligible for the use of gilteritinib. MOA: The FLT3 receptor’s internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations may both be inhibited by gilteritinib, which has a strong selective inhibitory effect. AXL and ALK tyrosine kinases are likewise inhibited by gilteritinib, it is also stated. Cancer cell development is influenced by the molecules FLT3 and AXL. The phosphorylation of FLT3 and its downstream targets, such as STAT5, ERK, and AKT, can be inhibited by gilteritinib’s action. Major contraindications:Hypersensitivity towards this drug or any of the excipients |
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Glasdegib for AML |
| Generic name: Glasdegib Trade name: Daurismo Date of approval: November 21, 2018 [ref] Company name: Pfizer Inc. Uses: Adult patients with newly diagnosed acute myeloid leukemia who are over 75 years old or who have co-morbidities that prevent rigorous induction chemotherapy are recommended to receive glasdegib in conjunction with cytarabine. MOA: Disrupts the hedgehog pathway by inhibiting the smoothen (SMO) receptor, a transmembrane protein involved in hedgehog (Hh) signal transmission. SMO suppression of hedgehog signaling alters the control of cancer stem cell survival, which has an influence on tumor biology. This might hinder the emergence of medication resistance and stop relapse in AML patients. Major contraindications:None |
Venetoclax for AML |
| Generic name: Venetoclax Trade name: Venclexta Date of approval: October 16, 2020 [ref] Company name: AbbVie Inc. Uses: For the treatment of adult patients with small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), venetoclax is recommended. Additionally, it is used in conjunction with azacitidine, decitabine, or low-dose cytarabine to treat newly diagnosed acute myeloid leukemia (AML) in people 75 years of age or older, or in those who have comorbidities that prevent the administration of aggressive induction chemotherapy. MOA: This medication is a selective inhibitor of the anti-apoptotic protein, which regulates B-cell lymphoma 2. By directly attaching to the Bcl-2 protein, displacing proapoptotic proteins including BIM (a new member of the Bcl-2 family), inducing mitochondrial outer membrane permeabilization, and activating caspases, venetoclax aids in the restoration of the apoptotic process. Major contraindications:Strong CYP3A inhibitors at the start and during the ramp-up phase |
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Enasidenib for AML |
| Generic name: Enasidenib Trade name: Idhifa Date of approval: August 1, 2017 [ref] Company name: Agios Pharmaceuticals Uses: Indicated for the treatment of adult patients with isocitrate dehydrogenase-2 (IDH2) mutation-positive relapsed or refractory acute myeloid leukemia (AML). MOA: This IDH2 inhibitor is an oral, reversible, selective IDH2 inhibitor. It blocks the activity of mutant IDH2, which lowers levels of 2-hydroxyglutarate (2-HG) and promotes myeloid differentiation in vitro. Enasidenib’s ability to decrease 2-HG levels and induce blast differentiation may allow it to show therapeutic effectiveness in AML with IDH2 mutations. Major contraindications:None |
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Ivosidenib: One of the latest FDA-Approved AML Medications |
| Generic name: Ivosidenib Trade name: Tibsovo Date of approval: May 2, 2019 [ref] Company name: Servier Pharmaceuticals LLC Uses: Ivosidenib is an FDA-approved isocitrate dehydrogenase-1 (IDH1) inhibitor that is prescribed for the treatment of individuals with the following symptoms of a vulnerable IDH1 mutation:
MOA: Isocitrate dehydrogenase-1 inhibitor Tibsovo (ivosidenib) prevents cancer cells from differentiating by reducing the excessive synthesis of the oncometabolite 2-hydroxyglutarate (2-HG). Major contraindications:None |
Olutasidenib: One of the latest FDA-Approved AML Medications |
| Generic name: Olutasidenib Trade name: Rezlidhia Date of approval: December 1, 2022 [ref] Company name: Rigel Pharmaceuticals Uses: Adult patients with relapsed or resistant acute myeloid leukemia (AML) who have an FDA-approved test-detected susceptible isocitrate dehydrogenase-1 (IDH1) mutation should be treated with olutasidenib. MOA: Olutasidenib particularly inhibits IDH1(R132) upon delivery, preventing the oncometabolite 2-hydroxyglutarate (2HG) from being produced from alpha-ketoglutarate (a-KG). Major contraindications:None |
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