Ofatumumab

Developed by a company called Genmad and marketed by Genmad and GlaxoSmithKline under the name Arzerra, ofatumumab is a monoclonal antibody and a cancer treatment. “Monoclonal antibody” refers to the method by which the drug is made. It also indicated to chemists and doctors that it is a very large and complex molecule. Antibodies are produced in the body in response to disease, and giving a patient an injection of a monoclonal antibody drug essentially amounts to supplementing the natural immune system – or immunotherapy.

Ofatumumab is approved by the Food and Drug Administration for the treatment of leukemia. It is specifically labeled for chronic lymphocytic leukemia. Oncologists can use the drug for other types of cancer if they feel it is the best course of action. This is called off-label use. The drug is under investigation for use in other cancers and it is possible that in the future the labelling could be expanded to include other indications.

This drugs has to be given by injection. If they were swallowed, the digestive system would denature and break it down before it could be absorbed into the bloodstream. Ofatumumab is mixed into a solvent for delivery through an intravenous system. A typical regimen is once-per-week administration for eight weeks, followed by less frequent administrations.

The most basic definition of cancer is abnormal cell growth. A mutation occurs in the cell’s DNA and the normal cycle of cell growth and death becomes distorted. Cancer cells begin to grow out of control and unless stopped continue to replicate themselves until they form tumors. There are more that 200 different types of cancer; virtually any cell in the body has the potential to become cancerous. One of the more common types of cancer affects the lymphocytes and immune system. Two very closely related cancers of this type are chronic lymphocytic leukemia and follicular non-Hodgkin’s lymphoma. Chronic lymphocytic leukemia affects the lymphocytes in the blood and the bone marrow while follicular non-Hodgkin’s lymphoma affects the body’s lymphocytes, lymph nodes, and bone marrow.

Rituximab is another monoclonal antibody that is used for CLL, but ofatumumab may turn out to be more effective.

There is also investigation into the use of ofatumumab for treatment of arthritis.
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Science

Immunotherapy is still pretty new, and tweaking the immune system – or supplementing it which is what ofatumumab treatment is – raises concerns about side effects. Drugs are thoroughly tested before the FDA approves them, but monoclonal antibodies warrant particular observation.

Side effects

All drugs have side effects. Conventional chemotherapy drugs have side effects generated by their general cytotoxicity – they kill cells, healthy as well as malignant, and these effects are often loss or hair, nausea, anemia, etc. Immunotherapy drugs have different side effects because they are not attaching the cells. Muscle spasms and the common symptoms of infection – runny nose, etc. – are listed as the most common side effects. Other side effects are possible, and as with other cancer treatment regimens, the medical team typically monitors the early stage of treatment closely for serious side effects.

Vaccinations are of particular concern when people are receiving immunotherapy. Don’t get one – even a flu or tetnus vaccination – without first consulting with the doctor who is overseeing your cancer treatment.

Medline Plus

Generic

There is no generic version of ofatumumab available and there will not be for the foreseeable future. So-called “small molecule” drugs – which most pharmaceuticals are – qualify for generic production once the patent on them expires. For “biologics” – produced by biotechnological processes – which monoclonal antibodies are – the genericization process is not so straightforward. This is an industry-wide issue and some have called for Congress to pass a law to make it easier for generic production of biologics.

CLL – Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is classified as chronic since its progression is typically slower than many other forms of leukemia. CLL is the second most common leukemia in adults and it is most often diagnosed in older adults. For the years 2004-2008 the median age for a diagnosis of CLL was 72 years old. Less than 0.1% of those diagnosed are under 20 and only 0.2% are between 20 and 34. After the age of 55 the percentage increases dramatically with nearly 30% of those diagnosed being between 75 and 84.

CLL usually strikes women more than men; however in 2011 it was diagnosed in 6,050 women and 8,520 men. Those of the white race are more prone to chronic lymphocytic leukemia than those of other races as are those with a family history of blood or bone marrow cancers. CLL is also seen more often in those exposed to certain chemicals such as insecticides and herbicides, particularly Agent Orange used during the Vietnam War.

Initially CLL often has no symptoms, but occasionally may present with fatigue, fever, weight loss, enlarged but painless lymph nodes night sweats or frequent infections. Several procedures are used to confirm a diagnosis of CLL. These include blood tests such as a complete blood count to count the number and type of lymphocytes present and immunophenotyping to determine whether an increase in lymphocytes is due to the body’s reaction to infection, a blood disorder, or chronic lymphocytic leukemia. This test also helps predict how aggressive the abnormal lymphocytes may be. To choose a course of treatment and determine prognosis, a fluorescence in situ hybridization or FISH test examines the chromosomes of the affected lymphocytes to determine abnormalities. Occasionally other tests such as CAT scans and bone marrow biopsies are used to make a diagnosis.

Once a diagnosis is confirmed, treatment options are dependent upon the staging of the disease. CLL is staged by the designations 0 through IV. Stage I is early-stage while II and III are intermediate and IV is advanced. Most doctors prefer what is referred to as watchful waiting for stages 0 and I if no symptoms are present. For intermediate and advanced CLL chemotherapy, targeted drug therapy or bone marrow stem cell transplant may be required depending on the staging and overall health of the patient.

Since chronic lymphocytic leukemia interferes with normal lymphocyte production frequent infections are a common complication. The most frequent infections occur in the upper and lower respiratory tract. Those with CLL also have an increased risk for other types of cancer including lung cancer and cancers affecting the skin and digestive tract. A small percentage of people with CLL will develop immune systems disorders and a small number will develop a more aggressive form of leukemia known as diffuse B-cell lymphoma. The five year survival rate for chronic lymphocytic leukemia is 78%. In 2011 there were approximately 4,600 deaths from CLL in the United States.

Follicular non-Hodgkin’s lymphoma is another slow growing type of cancer with primary diagnosis in middle age. One out of every five lymphomas diagnosed in the United States is follicular non-Hodgkin’s lymphoma. The average age at diagnosis is 66 with only 5.5% of all cases diagnosed from childhood to age 34 as opposed to 45.3% diagnosed between 65 and 84. This type of non-Hodgkin’s lymphoma NHL usually strikes men and women equally; however in 2011 36,100 men and 30,300 women were diagnosed. Like CLL, follicular NHL affects those of the white race more often than others as well as those exposed to chemicals, especially benzene. Those with a weakened immune system and those with auto-immune disorders such as rheumatoid arthritis or Lupus are also at greater risk for developing follicular NHL.

The symptoms of follicular NHL are the same as for CLL; however, patients may also experience pain or tightness in the chest, shortness of breath, and a swollen abdomen. The definitive test to confirm diagnosis of follicular NHL is a biopsy. Immunophenotyping and the FISH test are used to help identify the specific type of lymphoma in order to determine treatment and other tests such as x-rays, CT scans, and MRI’s are often used to help determine the location and extent of any tumors.

Follicular NHL has its own specific staging based on a modified version of the International Prognostic Index. It incorporates factors such as age, hemoglobin levels and number of lymph nodes affected. Treatment protocols are the same as for CLL with the addition of radiation to treat any affected lymph nodes.

Complications include infections, auto-immune hemolytic anemia, and the usual side effects of chemotherapy and radiation. One in three patients will develop fast growing diffuse B-cell lymphoma. The five year survival rate for this type of NHL is 70%. In 2011 approximately 18,900 people died in the United States from non-Hodgkin’s lymphoma. Clinical studies have also found ofatumumab has efficacy in some lymphomas.

National Cancer Insititute