How Can Zanubrutinib Treat CLL?
- Zanubrutinib is a new, effective drug for chronic lymphocytic leukemia (CLL). It can significantly prolong the time you can live without a worsening of your disease or symptoms.
- In clinical trials, 78.4% of the patients did not experience any worsening of their disease 24 months after starting the medication.
- This medication is a form of targeted therapy called a Bruton’s tyrosine kinase (BTK) inhibitor. It blocks a protein expressed on the surface of CLL cells that promotes their growth.
- Zanubrutinib avoids many of the side effects of earlier BTK inhibitors, such as ibrutinib, which was associated with a significant risk of atrial fibrillation (abnormal heartbeat that can be deadly).
Zanubrutinib belongs to a class of medications called kinase inhibitors, which are highly targeted medications that can target and eliminate cancer cells while relatively sparing normal tissue, unlike chemotherapy. It inhibits Bruton’s tyrosine kinase (BTK), which is a protein expressed on the surface of certain WBCs. It plays a crucial role in the development and survival of normal WBCs. It also promotes the growth of cancer cells in leukemias and lymphomas. BTK inhibitors bind to the BTK proteins, preventing them from supporting cancer cell growth.Read More
What Is Chronic Lymphocytic Leukemia (CLL)RELATED: Chronic Lymphocytic Leukemia (CLL): Overview CLL is a slow-growing blood cancer. Specifically, it is a cancer of the white blood cells (WBCs), which are cells produced by the bone marrow but ultimately circulate within the blood and the lymphatic system. Bone marrow is the red spongy tissue that lines the inside of long bones also produces other life-sustaining components of the blood, including red blood cells (RBCs), and platelets.
CLL signals an abnormal number of WBCs or lymphocytes within the bone marrow and blood. Despite increased numbers, these leukemic WBCs are abnormal and lack the ability to fight off infections. Furthermore, as their number increases, they crowd out the bone marrow leaving little room to produce normal RBCs, WBCs, and platelets. This can lead to anemia (lack of RBCs), a vulnerability to infections (lack of WBCs), and an elevated risk of bleeding and bruising (lack of platelets), even after minor injuries.
CLL is the most common leukemia in older adults. An average patient is diagnosed around age 70. It is rare in people younger than 40 and even rarer in children. According to the American Cancer Society, around 59,610 new cases of leukemia will be diagnosed in the United States in 2023. One quarter or almost 18,000 of these will be CLL. This disease will also result in 4,490 deaths within the same year.
Symptoms of CLL
Oftentimes, CLL does not cause any symptoms and is only diagnosed when a routine blood test detects an abnormal WBC count. In some patients, symptoms could be present and may include:
- Fever with a body temperature 100(F) or higher for more than 2 weeks without any infections
- Fatigue, which is often severe and impairs the ability to work
- Unintentional loss of 10% bodyweight over 6 months
- Drenching night sweats for ≥ 1 month
- Frequent infections
- Shortness of Breath
- Easy bleeding and bruising
- Feeling full after eating small amounts of food
- Enlarging spleen, which can often be felt below the rib cage
- Swollen glands in the groin, armpits, and/or neck
RELATED: Chronic Lymphocytic Leukemia (CLL): Symptoms & Diagnosis
Overall Outlook & Treatment for CLL Patients
CLL is rarely curable, hence the term chronic within its name. However, patients with this condition can live for years without any symptoms or needing treatment. In fact, a small number of CLL patients, those with del13q14 but no other genetic mutations, may enjoy the same life expectancy without any treatment as those without CLL.
Many patients, however, will require treatment at some point in time. This usually happens when patients become symptomatic or when their symptoms start to worsen significantly. There are many different types of treatments available for patients with CLL. These include:
- Watchful waiting: Using this approach, patients are carefully monitored by their doctors with regular follow-ups. The overarching aim is to only start treatment once symptoms appear or start worsening. Many patients whose disease is only incidentally diagnosed because of blood tests may be excellent candidates for this approach.
- Chemotherapy: It uses drugs that are toxic to all growing cells, including cancer cells. It is usually given through an injection into a muscle or vein. Chlorambucil and bendamustine are two chemotherapy medications used for CLL. Although they can be highly effective, these drugs carry bothersome toxicities, such as immense nausea, vomiting, diarrhea, hair loss, et cetera.
- Immunotherapy: This form of therapy uses a patient’s own system to fight cancer. Lenalidomide is one such medication.
- Targeted therapy: These therapies exploit unique features of cancer cells and use drugs that target these features. BTKs, such as ibrutinib and zanubrutinib, are drugs that block the tyrosine kinase enzyme, which plays an instrumental role in the development of CLL. BCL2 inhibitors, such as venetoclax, are another class of targeted therapies, which block the BCL2 proteins that can be found on some leukemic cells. Monoclonal antibodies are proteins that can target different proteins present on many cancer cells. Rituximab is one such monoclonal antibody, which is commonly used for CLL treatment.
- New treatments are being continuously tested in clinical trials. For some patients participating in a clinical trial may be the best option, especially if their cancer has unique features, which are being evaluated in new clinical trials.
Scientific Studies Demonstrate Zanubrutinib’s Efficacy
RELATED: Changing the Way CLL is Treated: What are BTK Inhibitors?
The FDA approval of Zanubrutinib is based on the results of two phase-III clinical trials, the ALPINE and the SEQUOIA trials. Phase III trials constitute the most rigorous testing for any new treatment. The proposed drug is pitted against standard-of-care (SoC) treatments to determine whether it is inferior, equal, or superior to the SoC. A successful phase III trial offers physicians the highest level of evidence for the efficacy of a new treatment for any disease.
The ALPINE trial enrolled 652 patients with relapsed or refractory CLL who had received at least one prior course of treatment. These 652 patients were randomly assigned to receive either zanubrutinib or ibrutinib. The investigators measured progression-free survival (PFS), which is the time a patient lives without any worsening of their disease. The PFS at 24 months was 78.4% for the zanubrutinib and 65.9% for the ibrutinib group, a significant difference.
The SEQUOIA trial enrolled 590 patients with previously untreated CLL, who were randomly allocated to receive either zanubrutinib or bendamustine–rituximab. 24-month PFS was significantly higher for zanubrutinib than bendamustine–rituximab (85.5% vs. 69.5%).
The Side Effects of Zanubrutinib
The most common side effects include:
- Common cold-like symptoms
- Nausea and Vomiting
- Pains in bones, joints, muscles, neck, or back
- Spasms in muscles
Although very unlikely, some people may experience serious and/or life-threatening side effects, which include but are not limited to:
- Significantly elevated blood pressure that leads to headaches, dizziness, and changes in vision
- Blood in bowel movements
- Bleeding from the gums
- Easy bruising and bleeding after minor traumas
- Chest pain or pressure
- Shortness of breath
- Serious infections
- Reactivation of hepatitis B in patients who carry the virus
- Allergic reaction with symptoms such as rash, hives, swelling, itchiness, wheezing, and trouble breathing, among others.
- Development of new cancers
- Harm to unborn babies
Any of these side effects may require medical evaluation and management, as indicated.
It is important to emphasize that zanubrutinib is generally well-tolerated, and its side effects are usually mild. “Ibrutinib was associated with a relatively significant risk of [abnormal heartbeat], so we had to watch for that. The newer drugs, zanubrutinib in particular, are very well-tolerated. I have 90-year-old patients [who take the drug and] are not really aware of any toxicity at all,” relates Dr. LaCasce.
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