Monoclonal Antibody Therapy: Rituxan

Rituxan® is the brand marketing name of the monoclonal antibody rituximab. Rituxan was the first antibody developed and approved to target the cell surface protein CD20, which is commonly expressed in non-Hodgkin's lymphoma tumors of B-cell origin.

It first reached the US market in 1997 and was an immediate game-changer in cancer. It proved a long-held theory—that a monoclonal antibody could be used to selectively target cell surface proteins in a tumor, and do it both effectively and without the toxicity associated with conventional chemotherapy.

Rituxan: FDA approved indications for lymphoma patients

Rituxan is approved for a handful of similar lymphoma-related FDA indications. They are:

• For previously untreated follicular, CD20+, B-cell non-Hodgkin's lymphoma in combination with first line chemotherapy and, in patients who achieve a complete or partial response to this therapy, as single-agent maintenance therapy.
• For relapsed or refractory, low-grade or follicular, CD20+ B-cell non-Hodgkin's lymphoma as a single agent.
• For non-progressing (or stable), low-grade, CD20+ B-cell non-Hodgkin's lymphoma as a single agent following first-line CVP combination chemotherapy.
• For previously untreated diffuse large B-cell, CD20+ non-Hodgkin's lymphoma (DLBCL) in combination with CHOP chemotherapy (i.e. R-CHOP) or other anthracycline-based chemotherapy regimens.
• For previously treated or untreated CD20+ Chronic Lymphocytic Leukemia, in combination with fludarabine and cyclophosphamide (FC).

Rituxan with CHOP in NHLs

The most profound effect Rituxan has had on cancer patients has come through its addition to traditional CHOP chemotherapy for the treatment of aggressive NHLs of B-cell origin such as DLBCL.

Prior to Rituxan, doctors used the International Prognostic Index (IPI) to determine prognosis in DLBCL patients receiving CHOP chemotherapy. However the addition of Rituxan to CHOP chemotherapy was so profound in bettering the outcomes of patients with this disease that the IPI became the R-IPI or the Revised International Prognostic Index, with significantly higher survival rates than those offered by CHOP alone.

Rituxan in the Zevalin Regimen

Rituxan is an important component of the non-Hodgkin's lymphoma radioimmunotherapy regimen Zevalin.

Frequently Reported Side Effects of Rituxan

Some commonly reported side effects from Rituxan are listed below. They may occur months after infusion, and one should contact one's doctor immediately if they are observed:

• Low back pain, blood in urine, or painful urination
• Muscle contraction, weakness, tightness
• Breathing issues or rapid/slow heart rate
• Confusion, dizziness, weakness on one side
• Chest pain, nausea, sweating
• Fever, chills, body aches and other flu symptoms
• Ease of bruising
• Earache, mouth ulcers, skin sores
• Skin rashes
• Severe constipation
• Night sweats

Immunosuppression in Rituxan

What makes Rituxan so effective is its ability to selectively find and kill CD20 expressing B-cells. This is great when you have a cancer that is affecting those B-cells. However, Rituxan cannot differentiate between a cancerous B-lymphocyte and a healthy B-lymphocyte. It therefore has the effect of depleting the body of these cells, which are crucial to the function of the immune system. For this reason, people on Rituxan are considered to be immunosuppressed and may be vulnerable to infection.

However, this immunosuppression gave researchers the idea that Rituxan might therefore be a good treatment for auto-immune disorders. It is now also FDA approved in combination with methotrexate to treat adult patients with moderately- to severely- active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Warnings and Precautions with Rituxan

For all its efficacy, Rituxan has its problems, some of which are outlined below.

Infusion Reactions

Sometimes, people have severe reactions to Rituxan IV infusion and in rare instances they can be fatal. Symptoms include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and even potentially death. Often, to avoid allergic reactions, patients will be pre-treated with an antihistamine or with acetaminophen.

Tumor Lysis Syndrome

When cancerous cells die en masse, they can cause Tumor Lysis Syndrome (TLS), in which the contents of the cells spill out and become toxic to the body.

Hepatitis B Reactivation

Rituxan can cause the HBV virus to reactivate in patients who have been previously infected because of its immunosuppressant qualities. Such reactivation can take up to four months to occur following Rituxan infusion.

Progressive Multifocal Leukoencephalopathy (PML)

PML is an extremely rare fatal brain virus that has been observed among a small number of people having been treated with Rituxan.

Other adverse reactions included in the FDA warnings about Rituxan include mucocutaneous reactions, infection, cardiac arrhythmias, renal toxicity, and bowel obstruction and perforation.

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