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Tyrosine Kinase Inhibitor Therapy vs. Chemotherapy: What Works Better for CML?

Posted on May 06, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Emily Wagner, M.S.

Chronic myeloid leukemia (also known as chronic myelogenous leukemia, or CML) can be treated in different ways. Two common cancer treatments are tyrosine kinase inhibitors (TKIs) and chemotherapy. These methods work differently and produce different results, but accomplish the same goal of killing cancer cells.

Your doctor should discuss with you which treatment option is better suited to your specific case of CML. Factors that play into this decision include your age, overall health, CML phase, and any mutations in the cancer.

TKI Therapy for CML

Tyrosine kinase inhibitors (TKIs) take advantage of the genetic mutations CML cells have in order to treat the cancer.

CML cells contain an abnormal gene, BCR-ABL1 (also known as a Philadelphia chromosome), which forms when two pieces of different chromosomes break off and stick to each other. The BCR-ABL1 gene is not a normal gene, and it is not found in healthy cells.

The BCR-ABL1 gene makes a specific protein known as a tyrosine kinase. Tyrosine kinase proteins tell cells to grow and divide, which is important for creating new cells and repairing damage. However, cancer cells with a mutated BCR-ABL1 gene grow and divide independently, and cause disease.

TKIs are drugs that have been designed to inhibit the protein made by these genes, stopping the cells from dividing uncontrollably. There are first-, second-, and third-generation TKIs that have been developed to treat CML. TKI treatments work best in people with Philadelphia chromosome-positive CML.

When cancer drugs target specific mutations and proteins, they are known as targeted therapies. One benefit of targeted therapies is that they “target” the CML cells that contain the abnormal gene. Healthy cells are generally not attacked, meaning there are fewer serious side effects compared to chemotherapy.

Gleevec (Imatinib)

Gleevec (imatinib) was approved by the U.S. Food and Drug Administration (FDA) in 2001 as a first-generation TKI used to treat CML. Almost all people with CML who take imatinib respond well, and for many years. In order to maintain this response, the drug must be taken every day.

In some cases, imatinib may stop working over time because the CML cells become resistant to the drug (known as imatinib resistance). In cases of resistance, higher doses of imatinib can be given, or another TKI can be used.

Tasigna (Nilotinib)

Tasigna (nilotinib) was approved by the FDA in 2007 as a second-generation TKI for treating CML. It can be used to treat people with newly diagnosed CML in the chronic phase or in cases where CML is resistant to imatinib.

Sprycel (Dasatinib)

Sprycel (dasatinib) was approved by the FDA in 2006 as a second-generation TKI for treating CML. It can be used as a front-line treatment, but is also helpful for people who cannot take imatinib due to its side effects or because it was ineffective for their cancer.

Bosulif (Bosutinib)

Bosulif (bosutinib) was approved by the FDA in 2012 as a second-generation TKI for treating CML. It can be used to treat newly diagnosed cases of CML as a front-line treatment, but it can also be used as a second-line therapy.

Iclusig (Ponatinib)

Iclusig (ponatinib) was approved by the FDA in 2012 as a third-generation TKI for treatment of chronic-phase CML that is resistant to at least two other TKIs. It can also be used in the treatment of accelerated-phase or blast-phase CML. It is not recommended for people with newly diagnosed CML.

Chemotherapy for CML

Unlike targeted therapies (such as TKIs), chemotherapy uses cytotoxic (cell-killing) drugs that work mainly on cells that are quickly growing and dividing. Chemotherapy is referred to as a systemic therapy. CML cells that have an abnormal BCR-ABL1 gene are killed by chemotherapy. However, hair follicles and cells that line the stomach and intestines, which also divide quickly, can also be killed.

Before the invention of TKIs, chemotherapy was a main treatment for CML. Now, targeted therapies such as Gleevec and Sprycel are used as front-line treatments because they work much better and with milder side effects.

Chemotherapy is still used to treat some cases of CML — especially in people whose cancer becomes resistant to TKI therapy. Chemotherapy can also be used to prepare the bone marrow for a stem cell transplant. Examples of chemotherapy drugs used to treat CML include:

Asciminib recently obtained the FDA's breakthrough therapy designation. This means that it can be used, but more study results are awaited.

Combination Therapy Using TKIs and Chemotherapy

Numerous clinical trials have been conducted to look at treatment with both imatinib and chemotherapy. Studies using hydroxyurea or cytarabine with imatinib investigated whether the combination improved remission rates. Unfortunately, these therapies did not appear to be beneficial, and in some cases, caused unwanted side effects.

Talk With Others Who Understand

MyLeukemiaTeam is the social network for people with leukemia and their loved ones. Members come together to ask questions, give advice, and share their stories with others who understand life with leukemia.

Do you have chronic myeloid leukemia? Have you used chemotherapy or TKIs to treat it? Share your experience in the comments below, or start a conversation by posting on MyLeukemiaTeam.

Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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