Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia: What to Know

Medically Reviewed By: Eric S. Winer, MD

Drugs known as tyrosine kinase inhibitors, or TKIs, have revolutionized the treatment of chronic myelogenous leukemia (CML), a type of cancer in which the bone marrow produces too many semi-mature white blood cells. Prior to the introduction of these drugs in the early 2000s, standard first-line treatments for the disease reduced CML levels in only about 15-30% of patients, with only a small percentage having a molecular response — a drop in the DNA level associated with the disease. With TKIs, the complete response rate — the percent of patients with no signs of cancer — is about 90%, with a molecular response in more than two-thirds of patients. Before TKIs, the vast majority of patients with CML required a bone marrow or stem cell transplant. Today, very few do.

These drugs work by blocking an abnormal protein formed when parts of chromosomes 9 and 22 switch places. The swap causes two proteins to link up, creating a “fusion” protein known as BCR-ABL that drives CML. Five TKIs — imatinib, dasatinib, nilotinib, bosutinib, and ponatinib — have been approved by the U.S. Food and Drug Administration as standard initial therapy for adults with CML.

How long do TKIs work against CML?

For most patients, treatment with TKIs produces lasting remissions. Traditionally, patients have needed to continue taking the drugs to keep their CML under control, much as patients with diabetes take insulin or patients with hypertension take blood pressure medications for the rest of their lives.

What side effects do TKIs have?

Each of the approved TKIs can have a different set of side effects. The adverse effects are usually mild but can be severe. They can usually be alleviated with dose reductions or changes in medication. It’s important to discuss these with your physician when deciding which agent to take.

Can some patients stop taking TKIs?

Almost a decade ago, research suggested that many patients who met certain criteria could stop taking the drugs and remain in remission. Today, patients generally have the option to stop TKI treatment if they have been taking the drug for three years and have had no evidence of the DNA for BCR-ABL for two years ­— that is, an ultra-sensitive PCR test detects no cancer cells in their blood.

For patients who meet these criteria, the decision of whether to keep taking TKIs is colored by several factors. Among them:

  • TKIs can continue to be taken without negative long-term side effects if they are already well-tolerated.
  • Of patients who decide to go off treatment, about 40% will not need to resume it. If the disease does relapse, as shown by monthly PCR testing, it usually occurs within the first six months of stopping treatment.
  • Patients who experience a relapse virtually always go back into remission by resuming TKI treatment.

Personal considerations also play an important role. Patients who decide to continue taking TKIs may be anxious that stopping treatment will allow the disease to return. Many express a desire to stay with something that’s working for them. Others, however, are attracted to the opportunity to stop taking medication they may no longer need. The cost savings and a desire to avoid the side effects of TKIs can also factor in to the decision.

In weighing their options, patients can work closely with their oncologist to arrive at a decision they’re most comfortable with.

About the Medical Reviewer

Eric S. Winer, MD

Dr. Winer received his MD from The University of North Carolina School of Medicine in 1999. He completed his residency in Internal Medicine at Tufts Medical Center. He remained at Tufts Medical Center for a clinical hematology/oncology fellowship, which he completed in 2005.