December 4, 2019 / All Stories

Possibilities in CLL care: From lucky cancer to resistant clones

The evolution of care for CLL patients spotlights significant achievements and advancements.

Oncology experts reflect on the evolution of the standard of care for chronic lymphocytic leukemia. CLL is one of the most common types of leukemia, diagnosed in adults. Recently, investigators have discovered molecules and proteins that target the underlying defect in CLL cells. Many advances in the laboratory have led to clinical trials that have resulted in marked benefit in many patients, including some who now have undetectable disease.
 

The Beginning of CLL Care

For many doctors, if there is one type of leukemia that you are going to get, then chronic lymphocytic leukemia (CLL) would be the one to get. It was often wrongly considered “lucky” or “good” when comparing types of cancers. Why? Because it progresses more slowly than other types of leukemia in most patients, but not all and many may die with the blood cancer and not because of it.

For the last half century, chemotherapy was the only way to manage this blood cancer. In the 1970’s half of all patients would have disease progression within the first year. By 2010, with better chemotherapy, it would be four years before patients progressed. “But we have evolved well past that today,” explains Su Young Kim, M.D., senior medical director, AbbVie. Dr. Kim, whose focus is oncology research and development, saw patients who were treated with chemotherapy early in his career. Through this approach, the cancer is attacked with the medicine going into the bloodstream, which can be useful for blood cancers that can progress like CLL. In some cases, doctors had used bone marrow transplants, but it’s use has become less common among oncologists in part due to the progress in more targeted medicines.

This approach was abandoned by doctors some time ago according to Michael Hallek, M.D., Department of Internal Medicine and Center of Integrated Oncology at the University Hospital of Cologne in Germany, who also described early care for CLL as frustrating. “Due to the nature of this leukemia many patients were dying from infections or refractory cases where they didn’t respond to treatment,” says Hallek. “Many doctors often found themselves simply relieving the symptoms for CLL patients.”

Today’s possibilities in CLL care

Less than a decade ago, came new research and understanding. “I knew we were in a new era as I watched results from a particular trial come in for a newer approach. Most patient enrolled in studies of new compounds only stay on for a short amount of time before they progress. More than seven years later from when this particular clinical trial started, there are patients alive from the same clinical trial. It’s just amazing,” says Kim.

What changed?

Scientists discovered an enzyme called Bruton’s tyrosine kinase. BTK controls the rate at which b-cells multiply and survive.

Researchers also looked at a family of proteins known as BCL2 in CLL. CLL cells have high expression of BCL2 and this prevents the cancer cell from undergoing a natural cell death or apoptosis. Thus, focusing on this pathway, scientists found that a molecule would bind BCL2, thus allowing the cell to undergo a natural death.
 

Future for CLL research

CLL researchers around the world are now looking for ideal combinations to care for patients. Danelle James, M.S, M.D., Lead of Oncology Product Development at Pharmacyclics, an AbbVie company, is studying the results of combining current approaches with the hope, that’s shared by the International Workshop on CLL, that one day researchers will find a cure.

“We want to see if we can prolong life for a patient without having additional health concerns from CLL. We want a world where all patients with CLL can obtain a functional cure from their disease and not suffer complications or die from their leukemia,” says James who also pointed out we are still years away from those convincing findings.

And there’s one more area scientists are focused on as they look to the future – resistant clones. A resistant cancer cell is like an antibiotic-resistant infection. Because of a genetic defect, there can be cases of resistant cancer cells in CLL. If no therapy works to kill the cell, the cancer clone can escape and clone. The research of Dr. Hallek is now focused on this clonal evolution of CLL. The understanding of CLL has been promising thus far, but researchers are dedicated to making sure they’re pushing the boundaries of science so that every patient has a promising future despite a cancer diagnosis.

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