New Treatment Options For Acute Myeloid Leukemia

The traditional treatment for Acute Myeloid Leukemia is chemotherapy using cytarabine and anthracycline drugs. However, advances in the research of the pathophysiology of acute myeloid leukemia lead the way to recent developments in the different drugs used in chemotherapy. Since 2017, the Food and Drug Administration (FDA) of the United States has approved several drugs to treat AML. In this article, we will be exploring these recently approved drugs by the FDA  in terms of the indication for their use and the Overall Survival (OS) that the specific drug achieved. 

Acute Myeloid Leukemia: What You Need To Know

Acute Myeloid Leukemia (AML) is a type of cancer that mainly concerns the blood and the bone marrow. It affects the normal proliferation of blood cells in the bone marrow through the production of abnormal immature blood cells called leukemia cells. This production of abnormal cells can proceed unregulated and finally affects the production of normal blood cells. Leukemia cells can spread throughout the body via the bloodstream and form tumors. 

According to data provided by the Surveillance, Epidemiology, and End Results (SEER) program by the National Cancer Institute, AML will cause approximately 20,050 new cases and 11,540 deaths in 2022.  The data suggest that the disease is commonly found in adults among these cases. This cancer develops even further in individuals with these risk factors:

  • Old age: According to a 2015 research, the median age of AML patients is 68 years old.
  • Being Male: SEER data shows a 1.6 increase in male cases every 100,000 individuals.
  • Smoking: A 2014 study presented an association of smoking with increased risk of AML.
  • Previous treatments with chemotherapy or radiation therapy which can cause therapy-related AML (t-AML)
  • Exposure to a radiation-rich environment
  • Exposure to the chemical benzene
  • Being diagnosed with inherited disorders
  • History of blood disorders such as myelodysplasia-related disorders.

A Deeper Look Into AML

The latter half of the risk factors mentioned above are very specific. If you or someone you know falls within those mentioned risks, you might want to watch out for these symptoms of AML:

  • A feeling of weakness and fatigue
  • Onset of fever and headaches
  • Observed susceptibility to infections
  • Appetite loss or unexplainable weight loss
  • Unusual swelling, bruising and bleeding

When tested in the healthcare facility, screening for AML can be in the form of blood tests, bone marrow biopsy, or imaging tests such as CT scans or MRIs. Doctors can also perform molecular and genetic testing. They recommend genetic testing because AML arises from different biological influences with a typical cytogenetic origin. Mutations in our genes are the cause of most cancers. With AML, these are the factors that signal its development:

  • Fms-related Tyrosine Kinase 3 (FLT3): Mutation in this gene was found to be 15-25% in AML patients. This mutation promotes factor-independent growth that leads to malignancy.
  • Isocitrate dehydrogenase 1 and 2 (IDH1 & IDH2): Mutation in the IDH1 gene is found in 7-14% of all AML, while mutation in the IDH2 gene is found in 8-19%. This mutation affects the nature of differentiation of blood cells in the bone marrow.
  • CD33 Receptor: Around 80% of AML patients have leukemia cells that express the CD33 antigen. Scientists use the presence of this antigen in the patient as a target for antibody-based drugs.

Upon knowing these molecular factors in the treatment of AML, we are now ready to discuss the treatment of such cancer. Typically, there is an established approach and a newer approach to the treatment sparked by the recent advances in medicine. The approval from the FDA allowed the surge of research in developing new drugs for AML treatment.

Traditional Approach To Treating AML

Doctors treat AML in two phases. The short and intensive induction phase involves reducing leukemia cells in the bone marrow. The following procedure is the consolidation phase, which aims to remove most leukemia cells that are too small to detect. 

A subset of AML called Acute Promyelocytic Leukemia can include a third phase. This phase involves the treatment of the patient with low doses of drugs months or years after consolidation. 

Traditionally, the drugs used for chemotherapy of patients under 60 years old are cytarabine combined with an anthracycline drug. The standard therapy includes the “7 + 3 regimen” which involves taking cytarabine for seven days while also having anthracycline for the first three days.

Advances in medicine and AML research have provided newer drugs to treat the disease better. Doctors can now suggest targeted therapy for patients with FLT3 gene mutations or CD33 antigens. 

Newer Approach To Treating AML

In a 2019 review article, researchers discussed the effectiveness of new drug treatments approved by the FDA since 2017. We will be discussing each of these in terms of the indicator for which the drug should be used and the specific drug’s effectiveness in terms of median Overall Survival (OS). Median overall survival is a good indicator of the drug’s effectiveness because it shows how much time the patient remained alive after the date of diagnosis or treatment.

The list below shows the new drug treatment provided in case there is a presence of genetic mutations or antigens detected:

  • For newly-diagnosed AML patients:
    • Midostaurin + standard chemotherapy: For patients with FLT3 mutation. OS= 74.7 months
    • Gemtuzumab ozogamicin: For patients with CD33 antigens. OS= 4.9 months
    • Gemtuzumab ozogamicin + standard chemotherapy: For patients with CD33 antigens. OS= 25.4 months
    • CPX-351: For patients with t-AML or AML with myelodysplasia-related changes. OS=9.6
  • For Relapsed/Refractory AML patients:
    • Gilteritinib: For patients with FLT3 mutation. OS=9.3 months
    • Ivosidenib: For patients with IDH1 mutation. OS=8.8 months
    • Enasidenib: For patients with IDH2 mutation. OS=8.6 months
    • Gemtuzumab ozogamicin: Used for adult/pediatric patients with CD33 antigens. OS=8.4 months

The list above shows a higher OS on the drug treatment used for newly-diagnosed AML patients than the relapsed/refractory patients. This is especially evident in refractory patients because the leukemia cells have stopped responding to treatment.

This next list will be in terms of the drug indication for newly-diagnosed adults aged 75 years and above or having comorbidities that inhibit the use of intensive chemotherapy. Ranking according to their median overall survival (with year approved enclosed in parentheses):

  1. Venetoclax + hypomethylating agent (2018): OS=17.5 months
  2. Venetoclax + low dose cytarabine (2018): OS=10.1 months
  3. Glasdegib + low dose cytarabine (2018): OS=8.3 months
  4. Ivosidenib (2019): OS not reported

Readers should note that the facts described in this article are merely informational in nature. Patients should listen to their doctors because they know the best treatment for their condition. 

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