Treating Chronic Myeloid Leukemia by Phase (2023)

Treatment options for people with chronic myeloid leukemia (CML) depend on the phase of their disease (chronic, accelerated, or blast phase), their age, other prognostic factors, and the availability of a stem cell donor with matching tissue type.

Chronic phase

The standard treatment for chronic phase CML is a tyrosine kinase inhibitor (TKI) like imatinib (Gleevec), nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib (Bosulif). If the first drug stops working or it never really worked well at all, the dose may be increased or another TKI might be tried. Ponatinib (Iclusig) is an option after all of the other TKIs have been tried or if the leukemia cells later develop the T315I mutation (see more on this below).

Switching to another TKI is also an option if a person can't take the first drug because of side effects.

Rarely, people in chronic phase may be treated with an allogeneic stem cell transplant (SCT). This treatment is discussed in detail in Stem Cell Transplant for Chronic Myeloid Leukemia.

Monitoring treatment results

Monitoring the patient to see how they respond to treatment is very important. Blood counts are checked often. The blood is also checked with a polymerase chain reaction (PCR) test to measure the amount of the BCR-ABL gene. The bone marrow is checked, too, to see if the Philadelphia chromosome is there. Testing for the BCR-ABL gene or the Philadelphia chromosome is usually done about 3 months after a TKI is started, and then every 3 to 6 months after that. If the results show that treatment is working well, the patient stays on their current drug. If the results show that treatment isn’t working well, and the patient is taking the drug the way they should, a new drug or treatment may be needed.

If the CML is responding well to treatment, 3 months after starting treatment, the patient should have:

• A complete hematologic response (CHR), and
• Some type of cytogenetic response, and/or
• A reduction of the number of copies of BCR-ABL on the PCR test by 90% or more

If treatment is working well, 18 months after starting treatment, the patient should have:

• A complete hematologic response (CHR), and
• A complete cytogenetic response (CCyR), and/or
• A major molecular response (MMR)

For more on these different types of response, seeHow Do You Know If Treatment for Chronic Myeloid Leukemia Is Working?

How often is treatment successful?

Up to about 70% of people have a complete cytogenetic response (CCyR) within 1 year of starting imatinib, and the rate of CCyR is even higher with other TKIs. After a year, even more patients will have had a CCyR. Many of these patients also have a complete molecular response (CMR).

But even in patients in whom the BCR-ABL gene can no longer be found while on treatment, it’s often not clear if they are cured, so most people need to stay on a TKI indefinitely. In patients who have a deep, long-lasting response to treatment (usually for at least 2 or 3 years), some doctors might suggest stopping the drug for a time and closely monitoring with blood tests to see if the CML returns. In clinical trials so far, typically about half of these patients can stop treatment without the CML returning. Another option might be lowering the dose of the TKI, which can reduce side effects.

If the CML does return after stopping or lowering the dose of the TKI, it's been found to respond well when the original treatment is restarted.

If the first treatment doesn’t work

If the leukemia doesn’t respond well to the first treatment, there are several options.

• Increasing the dose of the drug. This helps some people, although the higher dose often has worse side effects.
• Switching to another TKI, for example from imatinib to dasatinib, nilotinib, or bosutinib. The doctor may check the CML cells for genetic changes (mutations) to help decide which drug would be best.
• Interferon or chemotherapy (chemo) may be tried for those who can't take the TKIs or those for whom they are not working,
• Stem cell transplant may be an option, especially for younger people who have a donor with a matching tissue type.

Treating CML after a stem cell transplant

Some people who have a stem cell transplant may not get a complete response. If they do not have graft-versus-host disease (GVHD) , doctors may try to get their new immune system to fight the leukemia. One way to do this is by slowly lowering the doses or stopping the immune suppressing drugs they are taking. This is done very carefully in order to have an anti-leukemia effect without getting too much GVHD. Patients are watched closely during this time. Another approach that helps some patients is an infusion of lymphocytes taken from the person who donated the stem cells for the transplant (called donor lymphocyte infusion). This can induce an immune reaction against the leukemia. Other drugs may also be helpful. Most experts agree that these patients should take part in a clinical trial.

In patients who do have GVHD after a stem cell transplant, boosting the immune system further is not likely to help. These patients are often treated with a TKI like imatinib.

Accelerated phase

When CML is in accelerated phase, leukemia cells begin to build up in the body quickly, causing symptoms. The leukemia cells often acquire new gene mutations, which help them grow and might make treatments less effective.

The treatment options for accelerated phase CML depend on what treatments the patient has already had. In general, the options are a lot like those for patients with chronic phase CML. But patients with accelerated phase CML are less likely to have a long-term response to any treatment.

If the patient hasn’t had any treatment, a TKI will be used. Imatinib (often at higher doses than used for chronic phase CML) is an option for most people. Most patients in this phase respond to treatment with imatinib, but the responses do not seem to last as long as they do in patients in the chronic phase. The newer drugs like dasatinib and nilotinib are often used in this phase, and other drugs are under study.

If the patient is already getting imatinib, the dose may be increased. Another option is to switch to one of the other TKIs. Sometimes the CML cells are tested to see if they have genetic changes (mutations) that may mean that a certain TKI is more or less likely to work (see the section below called CML with the T315I mutation). In CML without that mutation, ponatinib is an option after all of the other TKIs have been tried.

Interferon is another option, but it's also much less effective in this phase than in the chronic phase. Some patients have some response when chemo is added to the TKI, but these responses are usually shorter than 6 months.

An allogeneic stem cell transplant may be the best option for most patients who are young and healthy enough to have this treatment. Most doctors prefer that the leukemia be controlled, preferably in remission, before starting the transplant procedure. To achieve this, chemo will often be used.

In some cases, an autologous SCT may be an option to try to get the CML back into the chronic phase, but it's very unlikely to result in a cure.

Blast phase

In the blast phase of CML, the leukemia cells become more abnormal. The disease acts like an acute leukemia, with blood counts getting higher and symptoms appearing or getting worse.

For people with blast phase CML who haven't been treated before, high-dose imatinib may be helpful. But it works in a smaller number of people and for shorter lengths of time than when used earlier in the course of the disease. Newer TKIs, such as dasatinib, nilotinib, and bosutinib, seem to be better in this phase, particularly if they hadn't been used earlier. Ponatinib may also be used, but only after all of the other TKIs have been tried. Patients who respond to these drugs may want to consider a stem cell transplant, if possible.

Most often, the leukemia cells in this phase act like cells of acute myeloid leukemia (AML), but they're often resistant to the chemo drugs normally used to treat AML. Standard chemo for AMLwill bring about a remission in about 1 out of 5 patients, but this is usually short-lived. If remission does occur, it may be a chance to consider some type of stem cell transplant.

A smaller number of patients have blast cells that act like cells of acute lymphoblastic leukemia (ALL). These cells are more sensitive to chemo drugs. Remissions can be induced in about half of these patients with drugs like vincristine, prednisone, and doxorubicin, along with imatinib, if that hasn't been given yet. Like patients with ALL, these patients are at risk for having leukemia cells in the fluid that surrounds the brain and spinal cord, so they often get chemo (cytarabine or methotrexate) put directly into that fluid (like during a spinal tap). Radiation therapy to the brain is another option, but is used less often. For more information, see Acute LymphocyticLeukemia.

Allogeneic SCT is less successful for blast phase CML than for earlier phases, and the long-term survival rate is less than 20%. Still, it's the only known option that may cure the disease. It's more likely to work if the CML can be brought back to the chronic phase before the transplant.

Because most patients with blast phase CML can't be cured, palliative treatment (intended to relieve symptoms rather than cure the disease) is important. For instance, radiation therapy can help shrink an enlarged spleen or reduce pain from areas of bone damaged by leukemia. Chemo (usually with drugs such as hydroxyurea) may relieve some symptoms for a time.

Clinical trials of new combinations of chemo, targeted agents, and biologic therapies are important options.

CML with the T315I mutation

As was mentioned in the section about targeted therapy, in some patients on TKI treatment, the cancer cells develop a gene change called the T315I mutation that keeps most of the TKIs from working. If your CML stops responding to treatment with a TKI, another one may be tried. Your doctor may also check to see if the cancer cells have developed the T315I mutation. If they have, you may be switched to ponatinib or asciminib, which are the only two TKIs that work for CML with this mutation. If these drugs don’t work or you can’t take them because of side effects, you may be started on chemotherapy (chemo). Omacetaxine (Synribo^®) is a newer chemo drug that has been shown to help sometimes in this situation, but other chemo drugs may help, too.