What`s new in chronic myeloid leukemia research and treatment?

Studies of chronic myeloid leukemia (CML) are being done in labs and in clinical trials around the world.

Genetics of chronic myeloid leukemia

Scientists are making great progress in understanding how changes in a person's DNA can cause normal bone marrow cells to develop into leukemia cells. Learning about changes in the genes (regions of the DNA) involved in CML is providing insight into why these cells grow too quickly, live too long, and fail to develop into normal blood cells. The explosion of knowledge in recent years is being used to develop many new drugs.

Treatment

Sorting out the targeted drugs

Imatinib (Gleevec) has now been used for several years and has been shown to be very effective, but studies have shown that the other tyrosine kinase inhibitors (TKIs), such as dasatinib (Sprycel) and nilotinib (Tasigna), work at least as well as imatinib for patients who are just starting treatment. Which drug is the best treatment to use first is still being studied. Another approach would be to combine 2 or more of these drugs to treat CML. This approach is also being studied.

Can treatment be stopped?

A recent study looked to see if patients who had a complete molecular response (CMR) for at least 2 years while on imatinib could safely stop drug treatment (patients who are in CMR have no signs of CML even with the most sensitive testing). Results showed that a little less than half of the patients who stopped were still without any signs of disease (and still in CMR) 12 months later. But, imatinib worked again for the patients whose CML came back. More research is needed to see if which patients can safely stop taking their TKI for CML.

Combining the targeted drugs with other treatments

Imatinib and other drugs that target the BCR-ABL protein have proven to be very effective, but by themselves these drugs don't help everyone. Studies are now in progress to see if combining these drugs with other treatments, such as chemotherapy, interferon, or cancer vaccines (see below) might be better than either one alone. A recent study showed that giving interferon with imatinib worked better than giving imatinib alone. The 2 drugs together had more side effects, though. It is also not clear if this combination is better than treatment with other TKIs, such as dasatinib and nilotinib. Studies are also looking at the role of different treatments combined with stem cell transplants.

New drugs for CML

Because researchers now know the main cause of CML (the BCR-ABL gene and its protein), they have been able to develop many new drugs that might work against it.

In some cases, CML cells develop a change in the BCR-ABL oncogene known as a T315I mutation, which makes them resistant to many of the current targeted therapies (imatinib, dasatinib, and nilotinib). Ponatinib (Iclusig) is a new drug that often works against T315I mutant cells. More drugs aimed at this mutation are now being tested.

Other drugs called farnesyl transferase inhibitors, such as lonafarnib and tipifarnib, seem to have some activity against CML and patients may respond when these drugs are combined with imatinib. These drugs are being studied further.

Cancer vaccines

Cancer cells are different from normal cells, so it is sometimes possible to get the body's immune system to react against them. One way to do this is to use a cancer vaccine - a substance injected into the body that boosts the immune system and causes it to attack certain cells. Several vaccines are now being studied for use against CML. For instance, in one small study, a vaccine called CMLVAX100 was given along with imatinib and seemed to increase its effectiveness. Research into this and other vaccines is continuing.