A 'Bright Future' For CLL
- Advances in targeted therapies have dramatically improved survival and quality of life for people with chronic lymphocytic leukemia (CLL), making it possible for many to live with the disease for years.
- BTK inhibitors and the BCL-2 inhibitor venetoclax have largely replaced chemotherapy for many CLL patients because they are more effective and generally better tolerated.
- Some patients eventually become resistant to current treatments, highlighting the need for new therapies. Promising treatments in development include CAR T-cell therapy, BTK degraders, bispecific antibodies, MALT1 inhibitors, and other targeted drugs.
- Researchers are excited about the future of CLL treatment, with ongoing advances expected to provide even more options for patients. Dallas-based hematologist Dr. Yair Levy says emerging therapies are producing “amazing data” in clinical research. “There is certainly a very bright future for CLL.”
Dr. Yair Levy, a hematologist with Baylor University Medical Center in Dallas, Texas, tells SurvivorNet “the therapies are better-tolerated and they’re only getting better.” Dr. Levy credits drugs like Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inibitors with improving patients’ quality of life due to more tolerable side effects.
Read MoreHow CLL Treatment Has Improved
These targeted therapies, which stop CLL cells from growing, have been phasing out chemotherapy treatment for CLL patients. Another advantage to these medications is that you take them by mouth, unlike chemotherapy, which is usually delivered intravenously (directly through a vein) into the bloodstream. According to Dr. Levy, today’s therapies offer several important advantages, including:- Longer survival
- Fewer toxic side effects
- A chance to avoid chemotherapy
Medications such as BTK inhibitors are at the forefront of these advances.
Covalent BTK inhibitors — including ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) — bind permanently to the protein BTK, while non-covalent BTK inhibitors, such as pirtobrutinib (Jaypirca), attach in a reversible way.
A BCL-2 inhibitor called venetoclax (Venclexta) can also be used to treat CLL and is primarily used in combination therapy, giving remarkably longer progression-free survival.
What’s Next in CLL Research?
Although treatment options for chronic lymphocytic leukemia (CLL) have improved dramatically, Dr. Levy says there are still important “unmet needs.” Some patients eventually become resistant, or refractory, to both BTK inhibitors and BCL-2 inhibitors, meaning the treatments stop working.
“For many patients, this can take years and years, but it’s still a high unmet need, even today,” he says.
Researchers are now studying several next-generation therapies that could offer new options for patients whose disease no longer responds to current treatments, including:
- CAR T-cell therapy, which reprograms a patient’s own immune cells to recognize and attack cancer cells.
- BTK degraders, which destroy the BTK protein rather than simply blocking it.
- Bispecific monoclonal antibodies, which are lab-made proteins that help direct the immune system to attack cancer cells.
- MALT1 inhibitors, which block the MALT1 protein involved in cancer cell growth.
- Other small-molecule inhibitors that target different pathways driving CLL.
Dr. Levy says the early results are especially encouraging for CAR T-cell therapies and BTK degraders.
“We can actually degrade the protein and therefore also interrupt that signaling pathway,” he explains of BTK degraders, “which are looking absolutely fantastic.”
He also points to “amazing data” emerging for bispecific antibodies, MALT1 inhibitors, and other small-molecule therapies currently in development.
Taken together with advances in combination therapies, Dr. Levy believes these innovations point to “a very bright future for CLL.”
Questions To Ask Your Doctor
- Is targeted treatment the best option in my case?
- What side effects can I expect from targeted treatment?
- What are my options if my cancer progresses despite treatment?
- Are there any clinical trials I should consider?
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