Treatments for AML have evolved significantly over the past 5 years. 

Currently, there are seven types of treatment options that can be used:

• Chemotherapy
• Radiation therapy
• Chemotherapy with stem cell transplant
• Targeted therapy
• Maintenance therapy
• Clinical trials
• Supportive therapy

The type of treatment a patient receives depends on several factors: age, health status, level of fitness, genetic mutations, AML classification and the patient’s goals. 

Here is a more in-depth review of the types of treatment options:

Chemotherapy 

This is the main form of treatment for AML. Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. The drugs may be given intravenously or orally. 

Chemotherapy for AML often occurs in two phases: induction and consolidation. 

Induction therapy is the first phase of treatment. It is a short and intensive treatment with the goal of quickly removing as many leukemia cells as possible. This hopefully puts the AML into remission. The treatment is usually made up of two drugs, cytarabine and an anthracycline drug, either daunorubicin or idarubicin. Cytarabine is given continuously for 7 days, and the anthracycline drug is given in 3 daily doses during the first 3 days. This regimen is called “7+3”. A third drug may be added to increase the chances of remission for people with certain AML subtypes. 

• For patients whose leukemia cells have an FLT3 mutation, the targeted therapy drug midostaurin (Rydapt) might be added. This drug is taken twice daily as a pill.
• For patients whose leukemia cells have the CD33 protein, the targeted drug gemtuzumab ozogamicin (Mylotarg) might be added.

Typically a week after induction therapy is completed, a bone marrow biopsy will be collected. If it shows that the blasts make up less than 5% of the bone marrow, the leukemia is considered to be in remission. If it shows >5% blasts, another round of chemotherapy may be given either with the same drugs used before or with different drugs. Induction therapy typically gets rid of most of the cancer cells, but there is often some left behind. This is why consolidation therapy is important and necessary. 

Consolidation therapy or “post-remission” therapy, is the second phase of treatment. The goal of consolidation therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse. For patients less than 60 years old or those over 60 years old who are considered medically fit, consolidation options are typically several cycles of high-dose cytarabine and possibly an allogeneic stem cell transplant. If receiving cytarabine, it is given at very high doses, typically over 5 days. This is repeated about every 4 weeks, usually for a total of 3 or 4 cycles. An allogeneic stem cell transplant may occur after the cytarabine cycles. 

For those who may not be able to tolerate consolidation treatment, other therapies are considered. Lower dose cytarabine, azacitidine, venetoclax, glasdegib and other targeted therapies may be appropriate treatment options. 

Radiation Therapy

Radiation therapy uses high-energy radiation to kill cancer cells. It is usually not part of the main treatment of AML, but there are certain circumstances in which it could be used:

• If the AML has spread outside of the bone marrow and blood, such as to the brain and spinal fluid
• If the patient is going to undergo a stem cell transplant, radiation to the whole body may be administered prior to treatment
• If the patient is experiencing bone pain as a result of AML, radiation may be used to reduce pain if chemotherapy has not helped

Allogeneic Stem Cell Transplant

Allogeneic stem cell transplant is the most common type of stem cell transplant used in AML. In this type of transplant, stem cells come from someone other than the patient. A donor is usually a person whose tissue type closely resembles the patients. After completing consolidation therapy, the patient will receive an infusion of donor stem cells into their bloodstream where they will travel to the bone marrow to begin making new blood cells. It takes a few weeks for the donor cells to settle in your bone marrow and begin making new cells. Patients will remain in the hospital and receive blood transfusions and frequent monitoring until the bone marrow recovers.

Targeted Therapies

Targeted therapies are drugs that target specific parts of cancer cells. They can sometimes work better than certain chemotherapy drugs or may be added to chemotherapy regimens to improve their effectiveness. Because the type of leukemia cells are not the same in every person with AML, not all targeted therapies are appropriate for every patient. The type of targeted therapy a person needs depends on their subtype of AML, genetic mutations, chromosomal abnormalities and surface proteins that are present.

Here are some of the most commonly used targeted therapies:

FLT3 Inhibitors

Some people with AML have a mutation in the FLT3 gene. This gene helps the cells make a protein (also called FLT3) that helps the cells grow. By inhibiting this protein, AML leukemia cells are less likely to be able to grow. Midostaurin (Rydapt) and Gilteritinib (Xospata) are FDA-approved FLT3 inhibitors that are both taken orally. Midostaurin can be used in combination with chemotherapy drugs in newly diagnosed FLT-3 mutated AML. Gilteritinib can be used as a single agent in relapsed or refractory FLT3-mutated AML. 

IDH Inhibitors

Some people with AML have a mutation in either the IDH1 or IDH2 gene. These genes help the cells make IDH1 and IDH2 proteins. Mutations in these genes can stop blood cells from maturing the way they normally would. Using IDH inhibitors to block IDH proteins helps the leukemia cells to mature into more normal cells. Ivosidenib (Tibsovo) and Enasidenib (Idhifa) are FDA-approved IDH inhibitors that are both taken orally. Ivosidenib can be used in newly-diagnosed IDH1-mutated AML with patients who are at least 75 years old or who have conditions that exclude them from intensive chemotherapy. Enasidenib can be used in adults with relapsed or refractory IDH2-mutated AML. 

Gemtuzumab Ozogamicin (Mylotarg)

This is a monoclonal antibody-targeted therapy combined with a chemotherapy drug. Monoclonal antibodies are man-made immune proteins. This antibody specifically attaches to the CD33 protein which is found on the surface of most AML cells. This antibody attaches to the CD33 protein and allows the chemotherapy drug to enter the leukemia cell. Inside, the drug kills the cell when it tries to divide into new cells. It is FDA approved for newly diagnosed CD33-positive AML or relapsed or refractory CD33-positive AML. It can be used alongside initial chemotherapy or by itself. It is most often used in patients with newly diagnosed AML in combination with 7+3 chemotherapy.

BCL-2 Inhibitor

BCL-2 is a protein present in cancer cells that allows them to live longer. Venetoclax is a drug that inhibits this protein, interfering with the growth of the cancer cells. This drug is an oral drug that has been FDA approved for newly diagnosed AML in adults who are age 75 years or older, or for those who have comorbidities that preclude the use of intensive induction chemotherapy. It can be used in combination with azacitidine, decitabine, or low-dose cytarabine.

Hedgehog Pathway Inhibitor

The hedgehog pathway is a signaling pathway that can be overactive in leukemia cells. This overactivity can promote the growth, survival and proliferation of cancer cells. Glasdegib (Daurismo) is a drug that targets a protein in this pathway to restrict cancer growth and progression. This drug is FDA approved for newly diagnosed AML in patients who are 75 years old or older or who have conditions that keep them from tolerating intensive induction chemotherapy. It is taken orally and used in combination with cytarabine.

Maintenance Therapy

In acute myeloid leukemia (AML), the bone marrow produces abnormal cells that cannot mature and do not function properly. Resulting in abnormal cell build-up in the bone marrow and blood. Chemotherapy is the main maintenance treatment for AML. Maintenance chemotherapy may be given to people with AML with intermediate or unfavorable chromosome changes who cannot have a stem cell transplant. Maintenance chemotherapy is most commonly given as oral azacitidine (Onureg).

Onureg (azacitidine) is an antimetabolite, which means that it works by disrupting the DNA production of abnormal cells (hypomethylation), the genetic material that controls the growth and function of these cells. Causing the death of rapidly dividing cells, including cancer cells no longer responsive to normal growth control mechanisms. This could also restore normal function to genes critical for differentiation and proliferation.

This drug has been approved as maintenance therapy in adult patients with acute myeloid leukemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT).

Clinical Trials

Joining a clinical trial is a great way to access new drugs that are not yet widely available to most people with AML. Patients who participate in clinical trials can be some of the first to receive a treatment before it is available to the general public. Whether or not to participate in a clinical trial is an important conversation to have with your medical team.

Supportive Therapies

Sometimes a patient may choose to not undergo any treatment at all. The focus then becomes maintaining the highest quality of life possible. Supportive therapy includes managing side effects. This may include pain medication, blood transfusions and infection management.