What Are Monoclonal Antibodies and BCL-2 Inhibitors?
Monoclonal antibodies and BCL-2 inhibitors are cancer treatment drugs that cause the death of B cells, or B lymphocytes – infection-fighting white blood cells that are part of your immune system. In chronic lymphocytic leukemia (CLL), defective versions of these cells grow out of control and crowd out healthy blood cells.
Which Monoclonal Antibodies and BCL-2 Inhibitors Are Used to Treat CLL?
Two types of these drugs are approved to treat CLL.
How Do Monoclonal Antibodies and BCL-2 Inhibitors Work?
The two types of drugs work in different ways.
BCL-2 inhibitors. Normally, when cells are old or defective, your body sends them the message to die naturally. But CLL cells have too much of a protein called BCL-2, which blocks this process, allowing the cancer cells to live longer than they should. BCL-2 inhibitors attach to this protein and stop it from working, so cancer cells get the self-destruct signal.
Monoclonal antibodies. These are proteins made in a lab that act like parts of your immune system called antibodies. They find and attach to certain targets on the surface of cells. Obinutuzumab and rituximab look for the CD20 antigen, which is on the surface of B cells. Alemtuzumab looks for the CD52 antigen, which is on the surface of both B cells and other immune system cells.
When Are Monoclonal Antibodies and BCL-2 Inhibitors Prescribed for CLL?
Most people don’t start treatment for CLL in the early stages. It usually grows very slowly, and you may not have symptoms for years.
When you have so many abnormal B cells that you start having complications, or you have a hard time managing your symptoms, targeted these drugs could be part of your first treatment. You may also get one after you’ve tried a different type of CLL drug.
How Do You Take Monoclonal Antibodies and BCL-2 Inhibitors?
The BCL-2 inhibitor venetoclax is a pill you take by mouth.
The monoclonal antibody drugs are liquid infusions you get through a needle placed in a vein in your arm. One of them, rituximab, also comes as a shot that goes under your skin (Rituxan Hycela). You might be able to switch to this version after your first IV dose.
Most people have this type of treatment for a set amount of time. You take venetoclax every day for as long as your doctor prescribes it, gradually working up to the recommended dose to avoid side effects.
Most of the time, therapy with monoclonal antibodies is given in rounds, or cycles, like chemotherapy. Each round normally lasts 28 days, and you’ll probably have six of them.
These drugs are often prescribed together:
Venetoclax plus obinutuzumab. With this combination, treatment lasts a year. You’ll start with three weeks of obinutuzumab, then add venetoclax in week four. You’ll stop the obinutuzumab after six rounds, but continue to take venetoclax for the rest of the year. This is approved as a first treatment.
Venetoclax plus rituximab. This combination is a two-year treatment approved for people who’ve tried a different therapy. You’ll start with five weeks of venetoclax and add rituximab in week six. You’ll stop rituximab after six rounds, but continue to take venetoclax until the end of the second year.
Venetoclax. Some people can continue to take venetoclax for as long as it helps them. But limiting the amount of time you take this drug may keep the cancer cells from becoming resistant to it.
How Effective Are Monoclonal Antibodies and BCL-2 Inhibitors?
Targeted B-cell drugs can help bring CLL into remission for months or even years. That’s when you don’t have symptoms and your blood cell levels are within the normal range. They can also help you live longer. Here’s what research has found:
Are Monoclonal Antibodies and BCL-2 Inhibitors Safe?
Some of these drugs come with a boxed warning, which is the most serious kind of warning the FDA gives about the safety of prescription drugs.
These warnings apply to the monoclonal antibody drugs:
Alemtuzumab
- Problems like anemia and bleeding that come from low levels of blood cells
- An immune response to the medication called an infusion reaction
- Serious infections
Obinutuzumab
- Hepatitis B infection in people who’ve had the virus before
- PML
Infusion reactions and low white blood cell levels are the most common side effects of the monoclonal antibodies used to treat CLL.
Rituximab
- Infusion reactions
- Rash, blisters, peeling skin, or mouth sores
- Hepatitis B infection in people who’ve had the virus before
- Rare brain infection called progressive multifocal leukoencephalopathy (PML)
Venetoclax
Venetoclax doesn’t have a boxed warning, but it can also cause some serious side effects. The most common are:
- Low levels of white blood cells, red blood cells, and platelets (cytopenia)
- Infections
- Diarrhea
- Nausea
- Body pain
- Extreme tiredness
- Swelling in your hands and feet
While the possible side effects of these drugs can be very dangerous, most people don’t have them, and there are ways to lower your risk.
Infusion reaction. This is like an allergic reaction and can range from mild to life-threatening. It’s most common at the start of treatment and can happen right away or days after an infusion.
Your doctor will likely give you medications before each infusion to try to keep an infusion reaction from happening. These may include an antihistamine, a steroid, acetaminophen, or a combination. You’ll also be watched closely during these treatments.
Cytopenia. It’s recommended that you have blood tests every month to measure your levels of red cells, white cells, and platelets. If your doctor spots a problem, they may give you medicine to treat it and delay your next dose until it’s resolved.
Increased risk of infection. These drugs can weaken your immune system and make you more likely to get infections.
You might get antibiotics, antivirals, or antifungal drugs to help prevent them.
Vaccines are also an important tool to prevent infections. Most people with CLL are encouraged to get them to protect against the flu, COVID-19, pneumococcal pneumonia, RSV, and shingles. But if you’re taking one of these drugs, you shouldn’t get a vaccine that contains a live virus like the chickenpox or measles, mumps, and rubella vaccines.
You can also take other steps to stay healthy, like:
- Washing your hands often
- Staying away from sick people
- Wearing a mask if you have to be in a crowded place
- Avoiding things someone else has had in their mouth, like a toothbrush, spoon, or straw
Tumor lysis syndrome
It’s rare, but these drugs can cause a dangerous side effect called tumor lysis syndrome.
They destroy cancer cells quickly, which floods your bloodstream with waste products. If your kidneys can’t filter this out quickly enough, you could end up with kidney damage and a life-threatening electrolyte imbalance.
This can be prevented by:
- Drinking lots of water. You might need IV fluids in some cases.
- Taking medications to lower uric acid levels
- Slowly working up to the recommended dose of the medication
You’re more at risk for tumor lysis syndrome if you have a very high number of cancerous B cells in your blood when you start taking one of these medications.
If you have serious side effects, your doctor may pause your medication, lower your dose, or switch you to a different medication.
Who Should Not Take Monoclonal Antibodies and BCL-2 Inhibitors?
These drugs can hurt a fetus. You shouldn’t take them if you’re pregnant.
If you have liver disease, you may need a lower dose of venetoclax.
How Much Do Monoclonal Antibodies and BCL-2 Inhibitors Cost?
These medications can be very expensive. The list prices for obinutuzumab and rituximab are $9,000 and $5,000 for each infusion. Venetoclax costs about $17,000 for a month’s supply.
Monoclonal antibody infusions are covered by Medicare part B. Medicare prescription drug plans cover venetoclax, although your cost will depend on your plan and whether you’ve met your deductible. With Medicare Part D prescription coverage, you won’t pay more than $2,000 every year for out-of-pocket drug costs.
Monoclonal antibodies and BCL-2 inhibitors are often covered by health insurance you get from your job or through a federal or state marketplace. Check with your plan administrator to find out what you’ll pay.
With rituximab, biosimilar versions are available that may be less expensive.
If you need help covering your out-of-pocket costs, several resources are available. The Patient Access Network Foundation is a private charity that offers financial help to people who qualify. Other options include:
Drugmakers
Some treatments used in CLL are all made by the same company, Genentech. It has programs that can help you afford these medications:
- For people who have private or job-provided health insurance: Genentech Oncology Co-pay Assistance Program
- For people who don’t have health insurance, or whose insurance doesn’t cover these drugs: Genentech Patient Foundation
Clinical trials
If cost is keeping you from being able to take a monoclonal antibody or BCL-2 inhibitor, check with your doctor about whether you should consider a clinical trial. These are an important part of the process of developing new drugs.
Usually you can get the drug being tested for free. And even if you’re in the group of study participants that doesn’t get the new drug (called the control group), you’ll still get the best available care for CLL.
Clinical Trials of Monoclonal Antibodies and BCL-2 Inhibitors for CLL
A clinical trial is often the next step if you’ve tried the approved CLL treatments and the cancer comes back. Some of the things researchers are studying include:
- Which combinations of existing drugs work best
- When is the best time to start treatment
- New drugs in this class
- Combining rituximab with lenalidomide, a drug that activates immune cells called T cells to attack the cancer cells
How to get into a clinical trial
Your doctor can help you decide whether a clinical trial might be safe and helpful for you. They may even know about a study in your area you can join.
There’s also a government-run database of trials you can search at clinicaltrials.gov. Other resources include research and support organizations like the Leukemia and Lymphoma Society and the CLL Society, and drugmakers themselves.
Are Monoclonal Antibodies and BCL-2 Inhibitors for CLL Right for Me?
It can be hard to decide which treatment for CLL is best for you. There are many things for you and your doctor to consider.
The stage of the cancer. CLL usually grows very slowly, and it may be many years before you have symptoms. If the cancer was discovered in an early stage, you may not need to start treatment right away.
Your treatment history. Monoclonal antibodies and BCL-2 inhibitors can be a first-line treatment or come after you’ve had a different type of therapy. Your doctor will look at how you responded to earlier treatments.
Possible side effects. It doesn’t happen for most people, but monoclonal antibodies and BCL-2 inhibitors can cause dangerous and even life-threatening side effects. Talk with your doctor about whether you’re at higher risk for these and if you’re strong enough to manage them.
How you get the treatment. While venetoclax comes as a pill, it’s usually paired with a monoclonal antibody, which you get through an IV infusion. You’ll have to go to a treatment center at least once a month and have a needle placed in your vein for the therapy, which can take several hours. Even the injection form of rituximab takes an office visit.
Cost. These drugs can be very expensive, although they’re usually covered by Medicare and private insurance plans. Check with your plan about what you’ll pay out of pocket.