Monoclonal antibody therapies are a more specific therapy than chemotherapy. This means that they are directed at a target that is located on tumour cells, as opposed to normal body cells.
Monoclonal antibody therapies are treatments that get natural immune system functions to fight cancers. These drugs may be used in combination with other treatments or alone as a single treatment. Not only does this make for effective lymphoma treatment, it also reduces the side effects. This is because normal cells are minimally affected.
How does antibody therapy work?
One way the immune system attacks foreign substances in the body is by making large numbers of antibodies. An antibody is a protein that sticks to a specific protein called an antigen. Antibodies circulate throughout the body until they find and attach to the antigen. Once attached, they can recruit other parts of the immune system to destroy the cells containing the antigen.
Researchers can design antibodies that target a certain antigen, such as one found on cancer cells. They can then make many copies of that antibody in the lab.
Types of monoclonal antibody therapy
Some monoclonal antibodies (MABs) work by recognising specific proteins on cancer cells, others target proteins on the cells of the immune system. Each MAB only recognises one protein.
Some MABs trigger the immune system to attack and kill cancer cells. Common MABs that work this way in lymphoma include:
- Rituximab (MabTheraTM)
- Obinutuzumab (GazyvaTM)
- Ofatumumab (ARZERRATM)
- Alemtuzumab (CampathTM)
Rituximab (MabTheraTM)
What is rituximab?
Rituximab is the first monoclonal antibody that was developed, that has led to many other immunotherapies to be developed since, for many other cancers. Rituximab is also the most common monoclonal antibody that is used to treat many B-cell lymphomas. Monoclonal antibodies are proteins that are engineered to recognise certain other proteins. Once they recognise their target protein, they bind to them.
Rituximab is engineered to recognise a protein called CD20, this protein is found on the surface of B-lymphocytes. By binding to the CD20 protein, rituximab stops the growth of the B-lymphocyte. Rituximab destroys both normal and malignant B-cells that have CD20 on their surface. This drug stops abnormal B-lymphocytes from continuing to grow, divide and cause more lymphoma. Rituximab can be used in combination with other treatments such as chemotherapy.
There is another type of anti-CD20 monoclonal antibody. The second type is a new generation monoclonal antibody, called Obinutuzumab (GazyvaTM).
Indications for the use for lymphoma
Rituximab can be given for several non-Hodgkin lymphoma (B-cell malignancies):
- Diffuse large B-cell lymphoma (DLBCL)
- Primary mediastinal B-cell lymphoma (PMBCL)
- Grey zone lymphoma (GZL)
- Mantle cell lymphoma (MCL)
- Burkitt lymphoma (BL)
- Marginal zone lymphoma (MZL)
- Follicular lymphoma (FL)
- Waldenstroms macroglobulinemia (WM)
- Chronic lymphocytic leukaemia (CLL)
- Small lymphocytic lymphoma (SLL)
- Other non-Hodgkin lymphomas
Rituximab can be given for several different treatment reasons that include:
- First-line treatment
- Maintenance therapy
- Relapsed lymphoma
How is it given?
Rituximab can be administered intravenously (into the vein):
- Administered as an infusion, NOT as a bolus or push
- For 1st infusion, the recommended rate is 50mg/hour. Infusion rate can increase by 50mg/hr every 30 minutes if there are no adverse events
- Providing the 1st infusion is adverse event free, all subsequent infusions can be administered at a starting rate of 100mg/hour, with 100mg/hour rate increases every 30 minutes to a maximum rate of 500mg/hr.
Rituximab can be administered subcutaneously (SubCut – under the skin)
- Slow 5-minute push through a needle into the shallow layers of the skin. Often administered into stomach tissue or thigh.
Note: due to government funding and other funding reasons, rituximab is given as an outpatient or on the day of discharge if you are an inpatient. There are also different funding reasons why IV is given in favour of the subcutaneous injection.
Common side effects
- Nausea and vomiting
- Mucositis (sore mouth and mouth ulcers)
- Infusion related reactions
- Indigestion
- Peripheral neuropathy (numbness and tingling of the hands and feet)
- Tiredness
- Neutropenia (low white cell count)
- Thrombocytopenia (low platelets and increase in bruising)
- Worsening of pre-existing cardiac conditions
- Hepatitis B reactivations
- Infections
- Diarrhoea
- Constipation
- Skin rash
Further Information
Obinutuzumab (Gazyva)
What is Obinutuzumab (Gazyva)?
Obinutuzumab is a type 2 monoclonal antibody.
A monoclonal antibody is a type of therapy that has been designed to recognise a specific protein on the surface of a cancer cell. Once they recognise their target protein, they bind to them. This then alerts the body’s immune system to find and attack the cancer cell.
Obinutuzumab is engineered to recognise a protein called CD20, this protein is found on the surface of B-lymphocytes. By binding to the CD20 protein, Obinutuzumab stops the growth of the B-lymphocyte, and alerts natural killer cells to attack and kill. This process stops abnormal B-lymphocytes from continuing to grow, divide and cause more lymphoma.
There are two types of anti-CD20 antibodies, these two types are distinguished based on how they bind to the CD20 protein, and what mechanisms they use to kill target cells. The two types of anti-CD20 antibodies are:
- Type I anti-CD20 antibody – Rituximab
- Type II anti – CD20 antibody – Obinutuzumab
Indications for Obinutuzumab (Gazyva)
Follicular lymphoma (FL):
- 1st line in combination with chemotherapy to treat people with advanced disease
- 2nd line in combination with chemotherapy to treat people with follicular lymphoma who are refractory (did not respond) to rituximab or have relapsed during or within six months of receiving treatment with rituximab
Chronic lymphocytic lymphoma/leukaemia (CLL):
- 1st line in combination with chlorambucil to treat patients with CLL that is previously untreated
The safety and efficacy to use Obinutuzumab (Gazyva) in patients under 18 years of age has not been established.
How is Obinutuzumab (Gazyva) given?
For patients with Chronic Lymphocytic Leukaemia
Obinutuzumab is given as an intravenous (into the vein) infusion. Your first treatment will be given quite slowly to monitor you for any side effects.
Patients will receive 6 cycles of Obinutuzumab in combination with a chemotherapy tablet called chlorambucil. Each cycle lasts 28 days and the Obinutuzumab is given once per cycle followed by several weeks rest. This means that most patients will complete their course of treatment in 6 months. In the first cycle Obinutuzumab is given on Day 1, day 8 and day 15 followed by a week’s rest. For cycles 2-6 Obinutuzumab is given just once per cycle.
Obinutuzumab is given slowly to begin with. The first dose of Obinutuzumab is split into two smaller doses so that the patient can be monitored for side effects. A small dose will be given very slowly and then later that day or the following day the patient will receive the rest of the dose.
For cycles 2-6 the patient will receive the Obinutuzumab on day 1 of the cycle.
For patients who have Follicular Lymphoma
Obinutuzumab is given in combination with chemotherapy. There are 3 different types of chemotherapy that are given and include:
The treating doctor will recommend the best chemotherapy for the patient.
The number of cycles given depends on the type of chemotherapy given and each cycle will last 21 or 28 days depending on the chemotherapy. For the first cycle of treatment the patient will receive Obinutuzumab on day 1, day 8 and day 15 followed by a period of rest and recovery. For the remainder of the treatment Obinutuzumab is given just once per cycle.
Obinutuzumab is given slowly to begin with, so that patients can be observed for side effects. The infusion rate is increased gradually whilst the patient is being closely monitored.
After the initial 6 or 8 cycles of Obinutuzumab and chemotherapy, the doctor may continue treatment with Obinutuzumab for up to 2 years, given once every 2 months. This is known as maintenance therapy.
Common side effects of Obinutuzumab
- Nausea and vomiting
- Peripheral neuropathy (numbness and tingling of the hands and feet)
- Tiredness
- Neutropenia (low white cell count)
- Thrombocytopenia (low platelets)
- Worsening of pre-existing cardiac conditions
- Hepatitis B reactivations
- Infections
- Diarrhoea
- Skin rash
Further Information
Gazyva (Obinutuzumab) website where you can access more information and hear patients talk about their experience whilst receiving Obinutuzumab. Speak to your doctor to obtain an access code for the website.
Alemtuzumab (Campath)
Alemtuzumab (Campath) is a humanised monoclonal antibody.
Alemtuzumab targets a protein called CD52 on the surface of a type of white blood cell called mature B lymphocytes. In some cancers, the B lymphocytes are abnormal. The alemtuzumab sticks to all the CD52 proteins it finds. Then the immune system picks out the marked cells and kills them.
Indications of use
Alemtuzumab is still being used in Australia but due to new improved treatments it is being used less. It has been approved for the following conditions:
- Chronic lymphocytic leukaemia (CLL)
- As part of a stem cell transplant
Chronic lymphocytic leukaemia (CLL)
CLL patients have alemtuzumab as a drip (an infusion) over 2 hours. This is normally administered 3 times a week, for between 4 and 12 weeks.
The dose of the infusion must be increased gradually as alemtuzumab may be poorly tolerated. Infusion-related reactions include fever, hypotension, and gastrointestinal upsets. Nearly 90% of patients have rigors. Premedication with steroids, an analgesic and an antihistamine are recommended.
As part of a stem cell transplant
Patients usually have the same dose of alemtuzumab, for 5 days.
- Day-8
Alemtuzumab 10 mg (IV infusion) in 100 mL sodium chloride 0.9% over 2 hours
- Day -7 to -4
Alemtuzumab 10 mg (IV infusion) in 100 mL sodium chloride 0.9% over 2 hours
- Day 0
Stem cells infused
Possible side-effects
- Nausea
- Vomiting
- Stomach pain
- Diarrhea
- Loss of appetite
- Mouth sores
- Headache
- Anxiety
- Difficulty falling asleep or staying asleep
- Uncontrollable shaking of a part of the body
- Muscle pain
