The Effectiveness of Monoclonal Antibodies in Treating CLL

In the past, the standard treatment for chronic lymphocytic leukemia (CLL) was chemotherapy. However, over the past few years, doctors have been able to make use of new targeted therapies that attack cancer cells while reducing other damage done to the body. Monoclonal antibodies have been used as CLL treatment for at least twenty years. The medication targets a protein on CLL cells called CD20.

The CD20 antigen is found on B cells (which, in the case of CLL, are cancerous). The drugs target the protein then summon the patient’s own immune system to attack cancer cells. Monoclonal antibodies currently approved to treat CLL include:

• Obinutuzimab (Gazyva)
• Ofatumumab (Arzerra)
• Rituximab (Rituxan)

What are the Side Effects?

Dr. Nicole Lamanna, a leukemia specialist at Columbia University Medical Center, says some patients experience minor side effects when they initially begin taking this kind of medication, which is given intravenously, meaning through an IV infusion. Some potential side effects include:

• Blood pressure changes
• Fever
• Chills
• Rash

“We give pre-medications before somebody gets this medication to sort of mitigate that reaction, so it happens in about 10% to 20% of patients,” Dr. Lamanna explained. “Once they get through that, if they’re the 10% to 20% that get a reaction, we tweak. So, their body’s seen it now, and so the likelihood of them getting a subsequent reaction with other treatments is very low. This is generally well-tolerated.”

How Does Obinutuzumab Work?

The drug obinutuzumab, a CD20 antibody, is now being combined with other agents in certain treatment plans to potentially increase its effectiveness. This monoclonal antibody is usually most effective when used in combination with CLL targeted-therapy drugs, according to Dr. Julie Vose, chief of hematology and oncology at the University of Nebraska Medical Center’s Buffett Cancer Center.

Those drugs can include:

• A BTK inhibitor, which is an oral drug that targets a protein on the B cells called Bruton tyrosine kinase (BTK)
• A BCL2 inhibitor such as venetoclax, also taken orally, that targets the protein BCL2

Another potential side effect to be aware of is something called tumor lysis syndrome.

Dr. Vose discusses the potential side effects of obinutuzumab. 
“The issue with CLL is that if the patient has a lot of cells, they can be [susceptible] to a disease or entity called ‘tumor lysis syndrome,’” says Dr. Vose. “That’s where the cells — because the treatment is so effective — die all at the same time.”

Because the body can sometimes have issues clearing out waste from all these dead cells, tumor lysis syndrome can cause kidney problems, as well as an imbalance of electrolytes.

Patients receiving obinutuzumab need to be monitored carefully during treatment. This may require hospitalization during their first treatment and possibly for subsequent treatments.

Questions to Ask Your Doctor:

• Is treatment with a monoclonal antibody right for me?
• What side effects should I be aware of?
• How will I be monitored?
• How can I weigh the risk vs. benefits of these drugs?