Published on September 14, 2020
Aggressive Treatment Options for Chronic Lymphocytic Leukemia
Twenty-four years ago, Patient Power’s Andrew Schorr underwent aggressive treatment for chronic lymphocytic leukemia (CLL) — treatment that included a multi-drug chemotherapy cocktail, steroid infusions and a stem cell transplant, sending his disease into remission for 17 years.
Andrew recently interviewed Dr. Paul M. Barr, Associate Professor of Medicine and Director of the Clinical Trials Office for the Wilmot Cancer Institute in New York. Andrew and Dr. Barr discussed the latest CLL treatments, including more aggressive options for patients whose CLL has become resistant to standard therapies.
Clinical Trials Study Chronic Lymphocytic Leukemia Treatments
Single agents in the form of pills are often prescribed to treat CLL, a disease of the blood and bone marrow, but it’s difficult to know how effective these therapies will be and for how long.1
“There's no doubt that the BTK inhibitors have completely transformed how we treat CLL patients,” said Dr. Barr. “Unfortunately, the responses, the remissions, don’t last forever.”
Bruton’s tyrosine kinase (BTK) is a therapeutic target that can be used as first-line therapy, and BTK inhibitors like ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) work by shutting down the BTK enzyme.
“We can look at the clinical trial results and try to estimate for our patients when a drug may wear off; when the disease might become resistant,” Dr. Barr explained.
“Some patients can still enjoy a very long remission,” he added. “So, each individual patient needs to be monitored very closely along the way.”
Another drug being studied in clinical trials is venetoclax (Venclexta). Used in combination with other CLL therapies like ibrutinib, venetoclax has led to minimal residual disease (MRD) in clinical trial participants and is showing promising results.
When CLL Becomes Resistant to Standard Therapies
One challenge CLL patients may face is if and when the disease becomes resistant to standard therapies and more aggressive treatment is recommended.
“We start thinking about what are the clinical trial options? Do we have cellular therapy options? Should we use PI3K inhibitors? There are a number of different possibilities out there,” Dr. Barr said.
PI3K inhibitors are signaling pathways that control multiple cellular processes including metabolism, motility, proliferation, growth, and cell death.
CAR T-cell therapies — genetically modifying a patient’s own T cells to attack their cancer cells — and stem-cell transplants are also options for patients who need aggressive treatment for CLL. However, the toxicities in CAR T-cell therapies may be more than some patients can endure. Stem-cell transplants can be very effective but have risks as well. The risks (side effects) versus the rewards (longer progression-free survival) should all be taken into account.
Improving CLL Remission Rates with Combination Therapies
Another CLL treatment option currently being studied is the combination of oral therapies with more aggressive treatment options.
According to Dr. Barr, the goal is to improve the standard of care knowing that some patients will experience a progression of CLL at which time more hard-hitting therapies may be needed. The idea is to have different medications work as a team to knock out the cancer cells from different angles.
“The intent here is to drive deeper remissions to help prevent resistance while ideally, hopefully, providing a limited duration of therapy.” To learn more, watch "When Would My CLL Need Aggressive Treatment? "
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1What is Chronic Lymphocytic Leukemia? American Cancer Society.
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