People with the most common type of blood cancer, chronic lymphocytic leukemia (CLL), are living longer than ever before without their disease progressing. While cures for CLL patients are still rare, survival rates have improved steadily over the last 50 years, with nearly 90 percent of people diagnosed with CLL today surviving at least five years, and most for many years longer.
LLS will never stop working toward a cure for CLL and every form of blood cancer—but we’re also incredibly proud of how far CLL treatment has come.
That’s due in part to the incredible number of new, effective, and less toxic therapies that have become available in the past 10 years. LLS funding has supported the development of virtually every one of them in some way. And LLS has also worked tirelessly to ensure that patients have access to these new therapies.
In the words of our Chief Medical Officer, Dr. Gwen Nichols, “The lifesaving treatments LLS helps to develop are vital to improving outcomes and quality of life for blood cancer patients and their families, and we are proud of the progress we’ve driven. But helping patients access them is just as critical.”
Read more about how LLS is improving access to lifesaving blood cancer drugs.
Long-term CLL remissions with good quality of life rely on a series of new, well tolerated treatments
Most people don’t have symptoms when they’re first diagnosed with CLL. The diagnosis is most often based on abnormalities detected in routine blood tests.
At this early stage, a watch and wait approach is common. Careful monitoring is important, though, to know when to start treatment.
Once symptoms advance, today’s go-to treatments offer most patients long periods of remission, and a better quality of life compared to the three-drug chemotherapy combinations of the past.
Targeted therapy
Targeted therapy is the most common first approach when treatment begins. These are oral medicines that eliminate the need for a chemotherapy infusion. They work by attacking specific genetic targets on CLL cancer cells or substances in the body that CLL cells require to grow.
Targeted therapies that work on a protein called Bruton’s tyrosine kinase, or BTK, have revolutionized CLL treatment. The BTK protein causes stem cells to make too many white blood cells—the hallmark of CLL.
Several drugs block the action of the BTK protein: these are the BTK inhibitors ibrutinib, acalabrutinib, and zanubrutinib. More recently a different type of BTK inhibitor was approved, called pirtobrutinib. This drug can be used even for patients who have relapsed after treatment with one of the other approved BTK inhibitors.
Another newer approach are drugs that degrade, rather than inhibit, BTK protein. These drugs are showing great promise in clinical testing.
A different type of targeted therapy, called venetoclax, works by blocking a protein called BCL2 that cancer cells need to survive. Newer (second-generation) BCL2 inhibitors are in development, and two potential treatments have shown very promising activity in early clinical studies.
Most targeted therapies are provided as pills or capsules that patients can take at home. These therapies can significantly improve the quality of life of patients, cutting down the number of doctors and hospital visits.
Monoclonal antibodies
Monoclonal antibodies are a type of immunotherapy that uses the body's own immune system to specifically target cancer cells. Monoclonal antibodies that target a protein called CD20 are another revolution in CLL care.
White (B) cells, the kind affected by CLL, have high levels of CD20 on their surface, making these antibodies very effective in CLL treatment. Two CD20 antibodies are currently being used in the United States for the treatment of CLL: rituximab and obinutuzumab.
Monoclonal antibodies and targeted therapies are often combined to attack CLL from multiple angles. Combinations of BTK inhibitors and venetoclax with or without an anti-CD20 antibodies have shown very high efficacy in several clinical trials.
Such combinations are being used not just in newly diagnosed patients but also for people who experience a relapse of their disease. New drug candidates from all three classes with even better activity and fewer side effects are currently being tested in many clinical trials.
CAR T-immunotherapy and bispecific antibodies
Last year, the first ever CAR T-immunotherapy was approved to treat CLL in patients who did not respond to initial treatment or whose disease has come back after treatment. This personalized approach teaches the patient’s own immune T-cells how to hunt and destroy CLL cells, in this case by targeting the CD19 protein. Typically, this type of treatment is given just once. It is too early to know how big of an impact this treatment will have for CLL patients, but experts are watching closely.
Finally, an exciting new type of immunotherapy called bispecific antibodies is now being tested in CLL. Several of these therapies are already approved for different types of lymphoma and are now being used in clinical trials of high-risk CLL patients who have already relapsed after treatment with a BTK inhibitor. These bispecific antibodies are off-the-shelf and can more easily be used in a wider range of hospitals than CAR T therapies.
You can read more about immunotherapy here: Four Things You Need to Know about Immunotherapy.
What’s next for CLL patients?
The outlook for people with CLL is better than ever, but we need to keep working to improve it for more people. Today we have treatments that can be used continuously, unlike toxic chemotherapies of the past, to keep patients in long-term remission. This may not be a “cure” in the literal sense, but many people will be able to live normal, symptom-free lives, with minimal or no treatment side effects.
In the meantime, LLS continues to play a major role in advancing blood cancer treatments that will lead to the next groundbreaking therapies in precision medicine and immunotherapy for CLL and all forms of blood cancer.
We have roughly two dozen active grants amounting to more than $16 million committed to innovative CLL research. This includes exploring new combinations of existing treatments as well as finding brand-new ways to treat the disease and to ensure more patients get the most out of treatments we already have. We’re also working to figure out why treatments work better for some people than others or why treatments stop working quickly for some.
If you or a loved one need personalized disease, treatment or support information, contact our Information Specialists.
