Anti-CD20 monoclonal antibody drugs are a class of targeted therapies. These engineered proteins specifically identify and attach to a marker found on the surface of certain immune cells. They are a form of immunotherapy, leveraging the body’s own defense mechanisms.
Mechanism of Action
Monoclonal antibodies are laboratory-produced proteins that mimic natural antibodies. Unlike the broad action of natural antibodies, each monoclonal antibody binds to a single, specific target, much like a key fits a lock. For anti-CD20 drugs, this target is the CD20 protein on the surface of B-cells. B-cells are white blood cells involved in the immune response, producing antibodies and presenting antigens.
The CD20 protein is expressed on B-cells from early development to mature B cells. When an anti-CD20 monoclonal antibody is introduced, it circulates and selectively binds to the CD20 protein on B-cells. This binding initiates immune responses that lead to the destruction or depletion of these targeted B-cells. Mechanisms include antibody-dependent cellular cytotoxicity (ADCC), where immune cells destroy antibody-flagged B-cells, and complement-dependent cytotoxicity (CDC), where the antibody activates the complement system to lyse cells. Some anti-CD20 antibodies can also directly induce B-cell death.
Conditions Treated
Anti-CD20 monoclonal antibody drugs treat B-cell related cancers and certain autoimmune disorders. Their ability to selectively deplete B-cells makes them effective in diseases where these cells are cancerous or contribute to harmful immune responses.
For cancer, these drugs treat B-cell malignancies like non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). In these cancers, malignant B-cells proliferate uncontrollably. Anti-CD20 therapy aims to eliminate these cancerous cells. Rituximab, for example, was initially approved for non-Hodgkin lymphoma and often combined with chemotherapy for diffuse large B-cell lymphoma.
For autoimmune diseases, anti-CD20 therapies treat conditions like multiple sclerosis (MS) and rheumatoid arthritis (RA). In these disorders, B-cells mistakenly attack the body’s healthy tissues, causing inflammation and damage. By depleting these self-reactive B-cells, the drugs help to reduce the autoimmune attack. Ocrelizumab, for example, is approved for relapsing and primary progressive multiple sclerosis, and ofatumumab is used for relapsing forms of MS.
Specific Drug Examples and Administration
Several anti-CD20 monoclonal antibody drugs are used in clinical practice, each with specific indications and administration methods. Rituximab (Rituxan, Truxima, Ruxience, Riabni) was the first anti-CD20 monoclonal antibody approved for therapeutic use and is widely employed for various B-cell lymphomas, chronic lymphocytic leukemia, and autoimmune conditions like rheumatoid arthritis. Ocrelizumab (Ocrevus) is primarily used for relapsing and primary progressive multiple sclerosis. Ofatumumab (Arzerra, Kesimpta) is approved for chronic lymphocytic leukemia and relapsing forms of multiple sclerosis. Obinutuzumab (Gazyva) is another anti-CD20 agent used in chronic lymphocytic leukemia and follicular lymphoma.
Most anti-CD20 drugs are administered as intravenous (IV) infusions in a clinical setting. These infusions typically take several hours, especially the initial doses, due to the need for slow titration to manage potential infusion-related reactions. For example, Rituximab’s initial IV dose is administered slowly over 3.5 to 4 hours. Some newer formulations, such as a version of Rituximab and Ofatumumab (Kesimpta), offer subcutaneous (SC) administration. These subcutaneous injections can be given over a much shorter time, often a few minutes, and in some cases, can be self-administered, providing greater convenience for patients.
Potential Side Effects and Management
Patients receiving anti-CD20 monoclonal antibody drugs may experience various side effects, which are generally managed by healthcare professionals. One common category includes infusion-related reactions, which can occur during or shortly after the drug administration. These reactions may present as fever, chills, headache, influenza-like illness, or a rash. To minimize these reactions, patients often receive pre-medications, such as antihistamines, acetaminophen, or corticosteroids, before the infusion. If a reaction occurs, the infusion rate may be slowed or temporarily stopped until symptoms subside.
B-cell depletion, a primary effect of these drugs, leads to an increased risk of infections. B-cells play a role in the immune system, and their reduction can impair the body’s ability to fight pathogens. This increased susceptibility includes common infections, like upper respiratory tract infections, and more serious or opportunistic infections. Healthcare teams monitor patients for signs of infection, and some viral reactivations, such as hepatitis B virus, are screened for before treatment. Lower immunoglobulin levels, a direct result of continuous B-cell depletion, can further increase infection risk over time.