It’s a drug that’s keeping people with chronic myelogenous leukemia alive.
Researchers are now only scratching the surface of the potential of Gleevec and other drugs like it.
Before 2001, fewer than 1 in 3 people with chronic myelogenous leukemia (CML) survived more than five years after diagnosis.
Then, along came Gleevec.
Gleevec is a brand name for imatinib mesylate. It’s a tyrosine kinase inhibitor (TKI).
The U.S. Food and Drug Administration (FDA) approved the drug as a targeted treatment for CML in 2001.
Treatment for CML hasn’t been the same since.
A 10-year follow-up study showed that 83 percent of people using the drug survived 10 years, some well beyond the decade mark. They did so without unacceptable toxic effects.
When Bharat Shah of Atlanta, Ga., was diagnosed with CML, his life expectancy was between six months and three years. So, he enrolled in a clinical trial for Gleevec.
Now, 17 years later, he’s still going strong. He told NBC News that he continues to take the daily pill.
Aside from a little puffiness around the eyes, he doesn’t have any other side effects.
When compared with harsher chemotherapy drugs, Gleevec has been shown to produce fewer, milder side effects.
Swallowing a pill is also easier on patients than injections or lengthy infusions.
It may well turn out to be a transformative treatment for other cancers and other types of diseases.
How Gleevec takes on CML
Dr. Sean Fischer is a medical oncologist and hematologist at Providence Saint John's Health Center in California.
He calls Gleevec a revolutionary breakthrough for the treatment of CML.
Fischer explained that tyrosine kinases are proteins that send signals from the surface of a cell to its nucleus. This is necessary for normal cell function and division. But certain tyrosine kinases are a problem.
“In the case of CML, a tyrosine kinase called the ABL tyrosine kinase, generated by a specific chromosomal abnormality characteristic of CML called the Philadelphia chromosome, is constitutively active, producing the disease,” he told Healthline.
Gleevec, and other drugs like it, inhibit this tyrosine kinase.
“These medications have the potential to lead to remission of what was formerly a deadly form of leukemia,” said Fischer.
Dr. David S. Snyder, FACP, associate director of the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope in California, specializes in CML.
He’s been involved in clinical research of Gleevec and other TKIs for many years.
He told Healthline that the recent report published in The New England Journal of Medicine confirms the successful response to Gleevec in the majority of patients with CML. Most achieve a functional cure of CML.
Snyder said there are two points of note.
“Not all patients respond adequately and may need to be salvaged with more potent second or third generation TKIs [e.g. nilotinib, dasatinib, bosutinib, ponatinib],” he explained.
“Secondly, there have, fortunately, not been any serious, unexpected late adverse effects observed in patients treated with Gleevec. That contrasts to the experience with other TKIs, which have been associated with serious thromboembolic events, especially ponatinib, but also nilotinib and dasatinib, pleural effusions, and other cardiac effects,” Snyder continued.
Potential in treating other cancers
Research indicates that imatinib is also effective in treating other cancers.
This includes some forms of acute lymphocytic leukemia (ALL) in children.
According to Snyder, Gleevec targets the pathogenic driver of CML. But that’s not all it does. It also inhibits other tyrosine kinases.
That makes it useful in treating other malignancies. These include chronic eosinophilic leukemia and gastrointestinal stromal tumors (GIST).
“Other tumors that are driven by targetable tyrosine kinases may also be treatable with Gleevec,” said Snyder.
He also noted there are many other TKIs in development, or already approved, to treat some of these diseases, including a subset of lung cancers.
“There are over 90 known tyrosine kinases in humans,” Snyder explained.
Snyder said there have been some other unexpected, potentially beneficial effects noted for Gleevec.
“For example, Gleevec may help improve control of type 2 diabetes in some patients, perhaps by decreasing insulin resistance,” he said.
According to Fischer, there is a focus on using this type of drug to combat nonmalignant disease.
Nilotinib, which is a TKI similar to Gleevec, is also used to treat CML. It was found to affect activity in Parkinson’s disease, a neurologic movement disorder.
“This exciting discovery has prompted additional research to fully assess this medication’s potential impact in Parkinson’s disease. Alzheimer’s, another progressive neurologic condition producing dementia, has also been quite topical,” said Fischer.
He said that’s due to discovery of gene mutation in certain older adults. It may protect them from developing Alzheimer’s dementia.
“In a recent study published in the Proceedings of the National Academy of Sciences, Gleevec was noted to mimic the effects of the protective mutation. This observation has served as a model for further study and development of such drugs to fight Alzheimer’s dementia,” said Fischer.
“The platform for targeted therapy to treat nonmalignant conditions continues to evolve. The potential for breakthroughs is extremely exciting,” he said.