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Research in chronic myelogenous leukemia (CML)
We are always learning more about cancer. Researchers and healthcare professionals use what they learn from research studies to develop better practices that will help prevent, find and treat chronic myelogenous leukemia (CML). They are also looking for ways to improve the quality of life of people with CML.
The following is a selection of research showing promise for CML. We’ve included information from PubMed, which is the research publication database of the National Library of Medicine. Each research article in PubMed has an identity number (called a PMID) that links to a brief overview (called an abstract). We have also included links to abstracts of the research presented at meetings of the American Society of Clinical Oncology (ASCO), which are held throughout the year. You can find information about ongoing clinical trials in Canada from CanadianCancerTrials.ca and ClinicalTrials.gov. Clinical trials are given an identifier called a national clinical trial (NCT) number. The NCT number links to information about the clinical trial.
Researchers are trying to find better ways to help doctors predict a prognosis (how likely it is that the cancer can be successfully treated or that it will come back after treatment) for CML. They are also trying to determine the best treatment options based on certain characteristics of the disease, such as specific biomarkers. Biomarkers are substances, such as proteins, genes or pieces of genetic material like DNA and RNA, that are found naturally in the body. They can be measured in body fluids, including blood, lymph fluid and bone marrow, or on certain types of cells, such as cancer cells. Doctors can look for and measure these biomarkers to check if cancer is present or that it is responding to treatment.
Prognostic and predictive biomarkers for CML can be used to help plan treatment. Prognostic biomarkers can be used to identify people who have a greater risk that the disease will progress or come back after treatment (recur or relapse). Predictive biomarkers are used to identify people who are more likely to have a favourable or unfavourable effect from treatment compared to people without the biomarker. Researchers are looking at the following biomarkers to see if they can help doctors diagnose, predict a prognosis for and find out which treatments will benefit a person with CML:
- BCR-ABL (Blood, PMID 26729897; American Journal of Hematology, PMID 28718956, PMID 28466557; Oncology, PMID 29151104; Journal of Cancer Research and Clinical Oncology, PMID 28083711)
- clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph-) (Blood, PMID 28835440)
- NKG2TD (International Journal of Hematology, PMID 28795321)
- plasma biomarkers (Blood, PMID 27827824)
- NK cells (Leukemia, PMID 27890936)
Find out more about research in prognosis.
Researchers are looking for new ways to improve treatment for CML. Advances in cancer treatment and new ways to manage the side effects from treatment have improved the outlook and quality of life for many people with cancer. The following is noteworthy research into treatment for CML.
Targeted therapy drugs target specific molecules (usually proteins) that cause cancer cells to grow. Researchers are studying the following types of targeted therapy drugs in treating CML.
Tyrosine kinase inhibitors
Tyrosine kinase inhibitors are drugs that block the enzyme tyrosine kinase, which helps cells develop and grow. Imatinib (Gleevec) is the main targeted therapy drug used to treat CML. But 20% to 25% of people who take imatinib for CML develop resistance to the drug. When this happens, doctors offer these people different tyrosine kinase inhibitors.
Researchers are looking at the following tyrosine kinase inhibitors to see if giving them in different doses or combining them with other therapies will make them effective treatments for CML.
Pioglitazone is a drug approved to treat diabetes. Giving pioglitazone with tyrosine kinase inhibitors may be an effective treatment for people with CML. Although tyrosine kinase inhibitors are effective against CML, there are sometimes cancer cells called leukemia stem cells that can hide from tyrosine kinase inhibitors. Pioglitazone increased CML stem cell death when given with tyrosine kinase inhibitors in laboratory studies. Clinical trials are currently looking at pioglitazone along with tyrosine kinase inhibitors to treat CML (Cancer, PMID 28026860; ClinicalTrials.gov, NCT02730195).
Nilotinib (Tasigna) seems to be more effective than imatinib at treating newly diagnosed CML that is in the chronic phase. Clinical trials also show that treatment with nilotinib made it more likely that people with CML could stay in remission after stopping treatment (called treatment-free remission) (Leukemia, PMID 28218239; ASCP, Abstract 7003).
Ponatinib (Iclusig) is another tyrosine kinase inhibitor that researchers are studying as a treatment for CML in the chronic phase (Lancet Haematology, PMID 26436130).
Switching to nilotinib after imatinib treatment could improve molecular response in people with CML and is more effective than increasing the dose of imatinib. Few people with CML stay in remission after they stop treatment, so many people need to continue treatments for the rest of their lives. If switching to nilotinib improves molecular response, some people may be able to have treatment-free remission (Lancet Haematology, PMID 27890073).
Optimizing the dose of tyrosine kinase inhibitors for each person based on response to treatment is being studied in clinical trials. Certain people may benefit from a lower dose of tyrosine kinase inhibitor (British Journal of Haematology, PMID 28699641; Lancet Haematology, PMID 28566209).
Long-term follow-up after treatment with imatinib shows favourable results. Almost 11 years of follow-up studies show that long-term treatment with imatinib was not associated with any unacceptable long-term or late effects (New England Journal of Medicine, PMID 28273028; Leukemia, PMID 28804124).
Find out more about research in targeted therapy.
Stem cell transplant
Stem cell transplant replaces a person’s blood-forming (hematopoietic) stem cells. It is used when stem cells or the bone marrow has been damaged by chemotherapy drugs, radiation therapy or disease (such as cancer). The new stem cells make healthy blood cells.
Stem cell transplants may be used to treat CML. Researchers are studying the following types of stem cell transplant to see if they could be safer, easier and more effective for people with CML.
Reduced-intensity allogeneic transplant uses lower doses of chemotherapy or radiation therapy before the transplant. The lower doses don’t completely destroy the recipient’s bone marrow, so blood cell counts don’t drop as low as they do in standard stem cell transplants. For this reason, there is a lower risk for complications. This may be of great importance for older adults who can’t tolerate the higher doses of chemotherapy and radiation normally used with stem cell transplants (Annals of Hematology, PMID 28624905).
Tyrosine kinase inhibitor treatment given after stem cell treatment (called prophylactic targeted therapy) may help prevent a relapse of CML (Clinical Lymphoma, Myeloma and Leukemia, PMID 27297665; Leukemia, PMID 28218239; Oncotarget, PMID 27880933).
Predicting who will benefit from a stem cell transplant can help ensure people with CML get the right treatment. Response to prior treatment with tyrosine kinase inhibitors may predict prognosis of stem cell transplant (American Journal of Hematology, PMID 28543934).
Lowering the risk for graft-versus-host disease (GVHD) in people with CML who receive stem cell transplants is another area of research. Possible ways of reducing GVHD include studies of:
- antithymocyte globulin (ATG) (Cancer, PMID 28301690)
- vorinostat (Zolinza) plus tacrolimus or methotrexate (Blood, PMID 28784598)
Find out more about research in stem cell transplants.
Learn more about cancer research
Researchers continue to try to find out more about CML. Clinical trials are research studies that test new ways to prevent, detect, treat or manage CML. Clinical trials provide information about the safety and effectiveness of new approaches to see if they should become widely available. Most of the standard treatments for CML were first shown to be effective through clinical trials.
A condition that might happen after a stem cell transplant. Healthy stem cells from a donor (called the graft) attack a recipient’s (receiver’s) cells (called the host). The graft cells see the host cells as foreign and start to destroy them. Symptoms include jaundice, rash or blisters on the skin, dry mouth or dry eyes.