Considering Venetoclax for CLL:
- Venetoclax, is a promising CLL treatment that triggers cancer cell to self destruct, potentially improving therapy outcomes.
- Approved in 2016, the drug targets a specific protein, offering hope for enhanced treatment effectiveness.
- Venetoclax can be used alone or in combination with other therapies.
- While it is less likely to cause cardiovascular problems or hair loss compared to other CLL drugs, it may cause other side effects including tumor lysis syndrome, a serious condition that can lead to kidney failure, seizures, or death.
It targets a specific protein called the BCL-2 that helps cancer cells live longer. By effectively blocking BCL-3, it kills more cancer cells than traditional medications as it avoids harming healthy cells.
Read MoreWhat is Venetoclax?
Venetoclax was approved by the US Food and Drug Administration (FDA) in 2016 to treat patients with CLL and other leukemia patients who have already undergone prior treatments.The medication works by targeting BCL-2, a protein that helps cancer cells avoid death and resist various treatments. This action is crucial because BCL-2 is often found in high levels in blood cancers like CLL, allowing these cells to survive longer than they should.
By inhibiting BCL-2, venetoclax triggers a process called apoptosis, essentially telling the cancer cells to self-destruct.
“We see that when we treat a CLL with this drug, we can pretty much trigger the death of CLL cells almost overnight,” Dr. Choi notes.”Within hours, a white blood cell count might drop close to normal.”
Doctors now prescribe venetoclax to CLL patients whether they have a particular genetic mutation or not. It is used alone or combined with other medications.
Venetoclax is taken in pill form once a day with a meal and water.
The dose depends on the type and stage of each patient’s cancer, and other factors such as their overall health. Doctors sometimes gradually increase the dose over time to reduce the risk of side effects.
What other drugs is venetoclax usually combined with?
Choi says the particular combination offer each patient a tailored approach to treatment to improve outcomes and suit individual patient needs.
“Yeah, I think physicians, we want, we want to partner with our patients and, and decide together what the best thing for you will be,” Dr. Choi says.
“ And sometimes it’s based on tests that they’ve run, maybe certain factors about the CLL cells or genetic changes, but other times it’s really oftentimes centered on your preferences,” he adds.
Ibrutinib
Dr. Choi says that a lot of current trials are studying venetoclax in combination with BTK inhibitors, a class of drugs that block the BTK enzyme.
This enzyme plays an important role in the development and function of B cells, a type of white blood cell involved in the immune response. By inhibiting BTK, these drugs can help stop the growth and spread of CLL.
Ibrutinib is one such drug. It is known for its effectiveness in managing CLL, especially in patients who have relapsed or have certain genetic mutations that make their cancer harder to treat.
Choi says that combined with venetoclax, ibrutinib could lead to a more effective approach to controlling the disease and possibly reducing the risk of relapse.
“So we’ll see in the future if those become yet another excellent treatment option for our patients,” he comments.
Obinutuzumab
Combining venetoclax with a drug called obinutuzumab attacks cancer cells in different, but complementary, ways.
While venetoclax targets BCL-2, obinutuzumab is a special type of antibody that seeks out and attaches to CD20, a protein on the surface of B cells, including the harmful ones.
By teaming up, these drugs can fight cancer more effectively, making it harder for the cancer cells to resist treatment. This approach can be gentler and cause fewer side effects.
“We’re seeing some promising signs from that,” Dr. Choi says. “We’re inspired by, by our patients and their families and certainly motivated by them to keep the progress going.”
Rituximab
Venetoclax can also be combined with rituximab, an antibody that helps the immune system find and destroy B cells, including cancerous ones.
Related: What are BTK Inhibitors?
Who will benefit the most from Venetoclax?
CLL patients who have a genetic mutation called 17p deletion, or who have received at least one prior therapy tend to get the best results on venetoclax.
Dr. Choi has authored numerous papers looking at the results for venetoclax either alone or in combination with other drugs. Among the findings he and other researchers have noted:
- The VENICE study: Compared two treatments for people with CLL who had been treated with other drugs before. One treatment was venetoclax alone, and the other treatment was venetoclax plus rituximab. The study found that both treatments worked equally well for people with CLL.
- The MURANO study: Showed that venetoclax plus rituximab was better than bendamustine plus rituximab by 44.7% for living longer without cancer getting worse and by 49.1% for having no signs of cancer.
- The CLL14 study: Showed that venetoclax plus obinutuzumab was better than chlorambucil plus obinutuzumab by 24.1% for living longer without cancer getting worse and by 41.1% for having no signs of cancer.
- The CAPTIVATE study: Showed that ibrutinib plus venetoclax was better than ibrutinib alone by 58.4% for having no signs of cancer in the blood and by 56.9% for having no signs of cancer in the bone marrow.
What are the side effects of Venetoclax?
Like any drug, venetoclax can carry side effects. They may include:
- Low levels of white blood cells
- Diarrhea
- Nausea
- Anemia
- Infections
- Fatigue
Venetoclax can also cause a serious condition called tumor lysis syndrome (TLS), which is caused by the fast breakdown of cancer cells.
TLS can lead to kidney failure, seizures, and death.
To prevent TLS, patients need to drink plenty of fluids, take other medicines, and have regular blood tests.
“Most people don’t experience much as far as side effects,” Dr. Choi says.
He adds that venetoclax doesn’t have many effects on the cardiovascular system like many other CLL drugs do. It also doesn’t lead to other common cancer treatment side effects such as hair loss.
Related: Why Patients May Be At Risk ForTumor Lysis Syndrome
What should patients taking venetoclax avoid?
- Certain medicines, including strong CYP3A inhibitors, a class of drugs often given with other cancer drugs to make them work better. Taking them with venetoclax can increase side effects.
- Citrus including grapefruit, Seville oranges, and Starfruit. They may change the way the body processes the drug.
- Venetoclax is not safe for pregnant or breastfeeding women. It may harm the unborn or nursing baby.
- Women of childbearing age should use contraception while taking venetoclax and for some time after the last dose to avoid issues.
Patients taking Venetoclax should be closely monitored by their doctors and immediately report any symptoms.
How does Venetoclax compare to other CLL treatments?
For CLL, the standard of care varies based on factors such as:
- Disease stage
- Symptoms
- Patient age and health
- Leukemia cell genetics
Some early-stage CLL patients may not need immediate treatment. For these patients, doctors may recommend active surveillance or “watch and wait” to closely monitor the disease to see if it changes or starts causing symptoms.
Patients with more advanced or symptomatic CLL often require treatment which often includes targeted drugs used alone or in combination.Less commonly, CLL might be treated with radiation, surgery, or stem cell transplant.
Venetoclax, specifically, may offer improvements over other therapies by targeting leukemia cells more precisely. Potentially this can mean better outcomes with fewer side effects.
However, cost considerations are important.
Venetoclax is a specialty medication and can be costly. Price varies based on dosage, insurance, and the pharmacy.
It’s often covered by insurance, but coverage levels and patient costs can vary widely. Financial assistance programs and coupons may also be available.
Patients should consult their doctor, pharmacist, or insurance provider to understand the specific costs involved in their treatment plan.
Related: Western Diet May be Linked to CLL, Study Says
Questions for your doctor
When considering Venetoclax for CLL treatment, have a clear conversation with your doctor. You might ask:
- Is venetoclax recommended for my case?
- What are the possible side effects and how can we manage them?
- Will Venetoclax be combined with other treatments?
- How will my treatment progress be monitored?
- What are the costs and coverage?
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