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Researchers continue to study the causes, diagnosis, and treatment of acute myeloid leukemia (AML) at many medical centers, university hospitals, and other institutions around the world.

Genetics of acute myeloid leukemia (AML)

Researchers continue to make progress in understanding how normal bone marrow cells can develop into leukemia cells. It has become clear that there are many types of AML. Each type of AML might have different DNA (gene) changes that affect how it will progress and which treatments might be most helpful. Researchers continue to study how DNA changes specific to different AML types can help us understand how to best treat each person’s AML.

Detecting minimal residual disease

In recent years, highly sensitive tests have been developed to detect even the smallest amount of leukemia left after treatment (known as minimal residual disease, or MRD), even when there are so few leukemia cells left that they can’t be found by routine bone marrow tests.

Multiparameter flow-cytometry (MFC), quantitative polymerase chain reaction (qPCR), and next-generation sequencing (NGS) are tests that can be used to identify even very small numbers of AML cells in a biopsy sample. These tests are useful in determining how completely the treatment has destroyed the AML cells.

Studies are looking at how to best use the information from these tests. The presence of MRD affects a person’s outlook, as well as if they will need further or more intensive treatment.

Improving treatment for acute myeloid leukemia (AML)

Treatment for AML can be very effective for some people, but it doesn't cure everyone, and it can often cause serious or even life-threatening side effects. Studies are looking for more effective and safer treatments for AML. Doctors are studying how best to sequence and combine treatments for AML to best fight the disease.

Chemotherapy

Chemotherapy (chemo) is still the main treatment for most types of AML.

R?esearchers are looking for the most effective combination of chemo drugs that will also limit unwanted side effects. This is especially important for older people who might not be able to tolerate the side effects of current treatments for AML.

The effectiveness of chemo may be limited in some cases because the leukemia cells can become resistant to it over time. Research is now looking at ways to prevent or reverse this resistance by using other drugs along with chemo. They are also looking at combining chemo with newer types of drugs to see if this might work better.

Stem cell transplants

Researchers continue to refine stem cell transplants to try to increase their effectiveness, reduce complications, and determine which people are most likely to be helped by this treatment. Many studies are trying to determine exactly when autologous, allogeneic, and mini-transplants might best be used.

Targeted therapy drugs

Chemo drugs can help many people with AML, but these drugs don’t always cure the disease. Newer targeted drugs that specifically attack some of the gene changes seen in AML cells have become an important part of treatment for some people. These drugs don't work the same way as standard chemo drugs. Some examples include:

FLT3 inhibitors: In some people with AML, the leukemia cells have a change (mutation) in the FLT3 gene. Drugs called FLT3 inhibitors target AML cells with this gene change. F?LT3 inhibitors such as midostaurin (Rydapt), quizartinib (Vanflyta), and gilteritinib (Xospata) are now approved to treat people whose AML cells have an FLT3 mutation. Several other FLT3 inhibitors are now being studied as well.

IDH inhibitors: In some people with AML, the leukemia cells have a mutation in the IDH1 or IDH2 gene, which stops the cells from maturing properly. IDH inhibitors can help leukemia cells mature into normal blood cells. Some of these drugs, such as enasidenib (Idhifa), olutasidenib (Rezlidhia), and ivosidenib (Tibsovo), are now approved to treat AML with certain IDH gene mutations. Several other IDH inhibitors are now being studied as well.

BCL-2 inhibitors: Some people with AML have leukemia cells that make too much of a protein called BCL-2. Leukemia cells that have too much BCL-2 tend to be harder to kill with chemo drugs. BCL-2 inhibitors prevent the BCL-2 protein from working in cancer cells. Venetoclax (Venclexta) is a BCL-2 inhibitor that has been approved to treat AML with too much BCL-2 protein. Several other BCL-2 inhibitors are being studied as well. 

Researchers are also looking at newer types of targeted drugs to treat AML.

Immunotherapy drugs

Immunotherapy works to boost the body’s immune system to help fight off or destroy cancer cells.

Bispecific antibodies: A bispecific antibody consists of two antibodies that each attach to a different target. Once inside the body, this type of drug can act as a link to bring two types of cells close together. One antibody is usually designed to attach to a target on the leukemia cell, while the other is designed to attach to a target on immune cells (for example, T cells). When the bispecific antibody brings the leukemia cell and immune cell together, the immune system is alerted and starts to fight the leukemia cell. Several bispecific antibodies are now being studied for use against AML.

Antibody-drug conjugates (ADC): An ADC is a drug with two parts: an antibody designed to attach to a surface protein on cancer cells and a toxin meant to kill the cancer cells. When ADCs are injected into the body, they act like a homing device, bringing the toxin directly to the cancer cells, which kills them. ADCs are already used to treat some types of cancer, and some ADCs are now being studied for use against AML.

Immune checkpoint inhibitors: An important part of the immune system is its ability to keep itself from attacking other normal cells in the body. To do this, it uses 'checkpoint' proteins on immune cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Drugs called immune checkpoint inhibitors (ICIs) target these checkpoint proteins. They are already used in many other cancers, and they are now being studied for use in AML, especially combined with chemo or targeted therapy drugs.

Chimeric antigen receptor (CAR) T-cell therapy: For this treatment, immune cells called T cells are removed from the person’s blood and altered in the lab so they have specific substances (called chimeric antigen receptors, or CARs) that will help them attach to leukemia cells. The T cells are then grown in the lab and infused back into the person’s blood, where they can now seek out the leukemia cells and attack them.

This therapy has been shown to work in other types of blood cancers, although it’s not yet clear if it will work against AML. Researchers are continuing to study how this therapy might be used to treat AML.