The Changing Treatment Landscape for CLL
- CLL treatment has shifted away from chemoimmunotherapy toward targeted therapies, including covalent BTK inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib, as well as the BCL-2 inhibitor venetoclax. In several clinical trials, these therapies kept CLL under control longer than older chemoimmunotherapy regimens and were particularly important for people with high-risk changes such as deletion of part of chromosome 17 [del(17p)] and/or a TP53 mutation.”
- Multiple clinical trials over the past decade have demonstrated superior results with these novel agents, leading to more effective, individualized treatment strategies and expanding options beyond traditional chemoimmunotherapy.
- Patients now benefit from more personalized treatment plans, guided by genetic features, overall health, and treatment goals.
- These developments have allowed many patients to achieve strong responses with less toxicity.” to: “These treatments can keep CLL under control for long periods and often avoid some chemotherapy-related side effects. However, they have their own risks and monitoring requirements.”
Not everyone with CLL needs treatment right away. People without symptoms or other signs that the disease is becoming active may be monitored with regular visits and blood tests, an approach called active surveillance, or ‘watch and wait.’
Read MoreThe Benefits of BTK Inhibitors
Dr. Alkharabsheh explains that BTK inhibitors, or Bruton’s tyrosine kinase inhibitors, which block a protein that help CLL cells grow, have continued to improve since they were first introduced.
“The first-in-class Bruton’s tyrosine kinase inhibitor, which is an oral medication that we used in CLL called ibrutinib, has really improved patient outcomes based on many clinical trials,” he explains.
Expert Resources for CLL Patients
- CLL is Not Considered Curable So Treatment May Resume Years Later
- CLL Treatment: The Side Effects to Expect & Why Reporting All New Symptoms is Crucial
- CLL Treatment Decision Making — Exploring All Your Options To Find What’s Right For You
- An Oral Medicine for People With Relapsed CLL: Idelalisib
- Active Surveillance For Chronic Lymphocytic Leukemia (CLL)
Since ibrutinib became available, additional targeted therapies have been developed, including a new generation of BTK inhibitors.
“Subsequently, we had several phase 3 trials looking into a second-generation oral therapy. We call them covalent BTK inhibitors that also have shown better results compared to chemoimmunotherapy combinations,” Dr. Alkharabsheh explains.
BCL-2 Inhibitors & Combinations
Another treatment option is a class of medications called BCL-2 inhibitors. One example is venetoclax, which can be used with a monoclonal antibody.
“We have another class of medications called BCL-2 inhibitors, such as venetoclax, that, in combination with a monoclonal antibody, showed better results compared to chemoimmunotherapy,” Dr. Alkharabsheh explains.
The treatment landscape continues to expand as researchers study and develop new combinations of these targeted therapies.
Targeted therapy does not mean side-effect-free. Depending on the medication, BTK inhibitors may cause bleeding, infections, or heart rhythm problems, while venetoclax can cause low blood counts, infections, and tumor lysis syndrome and therefore requires a gradual dose increase and close monitoring.
For some patients, treatment can also be time-limited, meaning therapy is given for a defined period rather than continuing indefinitely. For example, venetoclax-based combinations can be given for a set duration of about a year, allowing some patients to have a period off treatment after completing therapy.
For patients with CLL, these advances mean treatment decisions can now be more individualized. Factors such as the genetic characteristics of the CLL, overall health, and treatment goals can help guide discussions between patients and their doctors about which approach may be appropriate.
Questions To Ask Your Doctor
- Do I need treatment now, or is active surveillance appropriate?
- Is there a targeted treatment combination you recommend in my case?
- What side effects should I look out for?
- How will I be monitored while I am undergoing treatment?
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