Targeted Therapy Drugs for Acute Lymphocytic Leukemia (ALL)

Targeted drugs for ALL with the Philadelphia chromosome (Ph+ ALL)

In about 1 out of 4 adults with ALL, the leukemia cells have the Philadelphia chromosome. This is an abnormal chromosome formed by the swapping of genetic material between chromosomes 9 and 22, which creates a new gene called BCR-ABL. Cells with the BCR-ABL gene make an abnormal protein that helps the cells grow.

Drugs called tyrosine kinase inhibitors (TKIs) have been developed to attack this protein. Examples include:

• Imatinib (Gleevec)
• Dasatinib (Sprycel)
• Nilotinib (Tasigna)
• Ponatinib (Iclusig)
• Bosutinib (Bosulif)

In people with Ph+ ALL, adding a TKI to chemo helps increase the chance that the leukemia will go into remission. Continuing on one of these drugs can also help keep the leukemia from coming back. If one TKI doesn't work (or is no longer working), another one might be tried.

These drugs are taken daily as pills or capsules. Imatinib is also available as an oral solution (under the name Imkeldi).

Common side effects include diarrhea, nausea, muscle pain, fatigue, and skin rashes. These are generally mild. A common side effect is swelling around the eyes or in the hands or feet. Other possible side effects include lower red blood cell and platelet counts at the start of treatment. All of these side effects can get worse at higher than usual doses of the drug. Other, more serious side effects can occur as well, depending on which drug is used.

Targeted drugs for ALL with a KTM2A gene change

In a small number of people with ALL, the leukemia cells have a type of change known as a translocation in the KMT2A gene. This causes the cells to make an abnormal KMT2A protein, which can combine with another protein called menin to help the cells grow.

Revumenib (Revuforj) is a menin inhibitor. It stops menin from combining with the KMT2A protein. This drug can be used to treat people with ALL whose leukemia cells have a KTM2A translocation, if the ALL is no longer responding to treatment or has come back (relapsed) after other treatments. Your blood or bone marrow can be tested to see if your leukemia cells have this gene change.

This drug is taken by mouth as pills, typically twice a day.

Common side effects of this drug can include nausea, vomiting, bleeding, diarrhea or constipation, fatigue, muscle pain, increased risk of infection, swelling in the arms and legs, and loss of appetite. 

This drug may cause serious heart rhythm problems. This might lead to an irregular heartbeat, which could be life threatening. Your doctor will check your blood mineral levels and get electrocardiograms (EKGs) to test your heart rhythm before and during treatment with this drug.

An important possible side effect of this drug is differentiation syndrome. This occurs when the leukemia cells release certain chemicals into the blood. It most often occurs shortly after starting treatment, but sometimes it can happen weeks or months later. Symptoms can include fever, coughing or breathing problems (from fluid buildup in the lungs and around the heart), dizziness or lightheadedness (from low blood pressure), urinating less often (from damage to the kidneys), and severe fluid buildup elsewhere in the body. It can often be treated by stopping the drug for a while and giving other medicines (such as dexamethasone or hydroxyurea).

Immunotherapy drugs for ALL

Some of the immunotherapy drugs used to treat ALL might also be considered forms of targeted therapy, because they work by attaching to specific parts of leukemia cells. Examples include:

• Blinatumomab (Blincyto)
• Inotuzumab ozogamicin (Besponsa)

For more information on these drugs, see Immunotherapy for Acute Lymphocytic Leukemia (ALL).