How Can BCL-2 Inhibitors Treat CLL?
- BCL-2 (B-cell lymphoma 2) inhibitors bind to and inhibit the activity of the anti-apoptotic protein BCL-2.
- The BCL-2 protein is over-expressed in CLL cells, so when it’s inhibited it can lead to cell death.
- BCL-2 inhibitors are one of several targeted therapies have been developed to treat CLL over recent years.
- These drugs can lead to really great responses, but they also bring the risk of serious side effects — and patients will need to be monitored closely.
A BCL-2 inhibitor called venetoclax (brand name: Venclexta) can be used to treat CLL. It’s one of several targeted therapies that experts who work in the field say “transformed” how the disease is treated.Read More
Targeted Therapy For CLL Treatment
Dr. Lamanna went onto explain how the standard of care has changed for CLL in recent years due to these incredible developments.
Dr. Nicole Lanamma explains how new drugs are changing the approach to CLL treatment.
“These are targeted therapies. [With] our traditional therapies for CLL, we had a class of drugs called purine analogs. These are old forms of intravenous chemotherapy used for a variety of cancers, not just CLL,” Dr. Lamanna says. “As we learn about CLL biology, we’re starting to get more targeted with our treatments, attacking not only the cancer cell but also the cells that may support its growth, development or migration. We’re learning to target different pathways that support the cancer cell.”
What To Expect With BCL-2 Inhibitors
Your doctor may suggest using the BLC-2 inhibitor venetoclax if you have a genetic change known as a 17p deletion or you’ve already tried at least one other treatment. Venetoclax is also approved as a first treatment for CLL when given in combination with a monoclonal antibody called obinutuzumab (Gazyva).
When the two drugs are given in combination, patients start on obinutuzumab — which is given as an infusion — a few times a week. Then they progress to one infusion per week, and eventually only monthly infusions.
Dr. James Gerson, a hematologist at Penn Medicine, explained that the first two months of treatment can be irritating due to the sheer number of appointments, but it gets easier afterwards.
Dr. James Gerson Explains What to Expect with Venetoclax
“It’s sort of the most annoying in the first three weeks, and then it gets less so, but it’s still a monthly infusion after that,” Dr. Gerson explained. “Then once you start the venetoclax, which usually starts near the end of the first month or the beginning of the second month, then you’re getting a lot of blood draws. Unfortunately, because of the risk to the kidneys, we have to keep a very close eye on the kidney function using blood work.
“So it’s oftentimes blood work the day before, blood work the day of, and blood work the day after,” he continued. He also noted that the drug will be administered in an increasing dose, “and each of those steps often requires all these blood tests. So, it’s a lot of blood and a lot of trips back and forth … it’s really annoying, but that’s the worse of it.”
What Are The Potential Side Effects?
One of the reasons patients receiving venetoclax need to be monitored so often is something called lysis syndrome, which occurs when tumor cells break open too quickly and release some of their toxins into the blood stream. This can be dangerous for the kidneys and the heart.
Other possible side effects include:
- Low white blood cell counts
- Upper respiratory tract infection
- Low platelet counts
- Low red blood cell counts
- Muscle and joint pain
- Swelling of arms and legs
Dr. Matthew Davids, the director of the Center for CLL at Dana-Farber Cancer Institute, stressed that while patients who are at high-risk may need to be hospitalized for the initial dose of venetoclax, the drug can be very effective, so it may be worth the precaution.
“Patients who are at high risk for tumor lysis syndrome do need to be hospitalized for their initial dosing of venetoclax,” Dr. Davids explained. “However, the responses to this drug can be excellent, and so for most patients, it’s worth investing some time getting started on the drug, to do so safely, and to achieve a good response.”
Questions to Ask Your Doctor
- Is treatment with a BCL-2 inhibitor right for me?
- What side effects/possible complications should I be aware of?
- Are there currently clinical trials I should consider joining for new targeted therapies?