Immunotherapies and Targeted therapies

There are many types of monoclonal antibodies. They can be referred to as a targeted therapy or an immunotherapy. Some monoclonal antibodies attach to a specific target on a cancer cell and stop it from growing. These are referred to as targeted therapies. They work by attaching to and blocking proteins on cancer cells (or other nearby cells) preventing cancer cell growth. Other monoclonal antibodies are called immunotherapy. They work by attaching to specific cancer cell proteins to tell your immune system to destroy those cells. They also slow down cancer cell growth.

Monoclonal antibodies may be given to people who are not suited to some chemo treatment due to its side effects. These may be given in combination with either chemotherapy or other targeted therapies. They are mostly given intravenously (IV), but some can be given subcutaneously (injection under the skin).

Monoclonal anti-CD20 antibody:

Rituximab and obinutuzumab are examples of monoclonal anti-CD20 antibodies.

• CD20 is a protein found on the surface of B-cells, it is found on the cell surface of some blood cancers
• this is termed CD20 positive
• the monoclonal anti-CD20 antibody connects to this protein on the blood cancer cell
• it destroys the cell by damaging the antibody, causing the cell to die
• it is used to treat Non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia (CLL)

Monoclonal anti-CD19 antibody:

An example of a monoclonal anti-CD19 antibody is blinatumomab

• targets a the CD19 protein found on some leukaemic cells so the immune system can kill them
• used to treat Acute Lymphoblastic Leukaemia (ALL)

Monoclonal anti-CD22 antibody:

Inotuzumab ozogamcin is an example of a monoclonal anti-CD22 antibody

• targets the protein CD22 and delivers a drug directly to the cancer cell to kill it
• used to treat Acute Lymphoblastic Leukaemia (ALL)

Monoclonal anti-CD30 antibody:

An example of a monoclonal anti-CD30 antibody is brentuximab

• targets a protein called CD30
• sticks to the CD30 protein and delivers a drug to the cell to kill it
• used to treat Hodgkin lymphoma and some lymphomas

Monoclonal anti-CD38 antibody:

Daratumumab is an example of a monoclonal anti-CD38 antibody

• targets the CD38 protein on myeloma cells so the immune system recognises it and kills the cell
• used to treat myeloma

Monoclonal anti-SLAMF7 antibody:

An example of a monoclonal anti-SLAMF7 antibody is elotuzumab

• targets a protein on myeloma cells called SLAMF7
• directly enhances immune system activity to kill the myeloma cell
• used to treat myeloma

Bispecific T-cell Engagers (BiTEs):

Blinatumomab is an example of a bispecific T-cell engager

• combine 2 different monoclonal antibodies
• attach to 2 different proteins at the same time
• they attach to a protein on cancer cells and to a protein on immune cells
• the immune cells and cancer cells come into contact to help the immune system kill the cancer cells
• used to treat Acute Lymphoblastic Leukaemia (ALL)

Side effects from monoclonal antibodies tend to be different to chemo side effects. If you’re having more than one type of drug, you may have a few different side effects at different times. Your treatment team will talk to you about what you might expect.

Infusion related reactions (appear during or soon after infusion) of monoclonal antibodies may include:

• itching
• chills and/or fever
• nausea
• fatigue
• shortness of breath/cough
• facial swelling
• lightheaded
• chest pain
• rash/hives
• headache

Side effects (appear within days-weeks) of monoclonal antibodies may include:

• body aches and pains
• headache
• constipation
• diarrhoea
• rash
• low blood counts
• infection
• shortness of breath/cough
• an irregular heart rhythm called atrial fibrillation
• bleeding

Immune checkpoint inhibitors

Immune checkpoints are a normal part of the immune system. However, sometimes cancer cells can evade the immune system by binding to checkpoint proteins. Immune checkpoint inhibitors are a type of monoclonal antibody. They don’t kill cancer cells directly. They work by:

• blocking checkpoint proteins from binding
• preventing the cancer cell from evading the immune system

Types of immune checkpoint inhibitors:

• PD-1 inhibitors bind to the protein PD-1 on the surface of immune cells
• Pembrolizumab and nivolumab are examples of PD-1 checkpoint inhibitors

Immune checkpoint inhibitors:

• are all given intravenously (IV)
• are used to treat Hodgkin lymphoma and some types of Non-Hodgkin lymphoma

Side effects of immune checkpoint inhibitors:

• rash
• diarrhoea
• fatigue
• inflammation (depending on the organ of your body that is affected):
  • skin – changes in skin color, rash, feeling itchy
  • lungs – cough, chest pain, shortness of breath
  • bowel – stomach pain, diarrhea
  • pancreas – diabetes, thirst, weight loss, blurred vision, fatigue
  • liver – yellow skin, eyes
  • pituitary gland – headaches, vision changes, nausea, vomiting
  • heart – chest pain, shortness of breath, fatigue, irregular heart rate, swollen legs
  • kidneys – high blood pressure, blood in urine, swelling in hands, feet, and face
  • thyroid – fatigue, weight gain or loss, feeling cold, slow or racing heart rate, irregular heart rate
  • nervous system – muscle weakness, numbness, trouble breathing

Some examples of immune system modulators are thalidomide, lenalidomide and pomalidomide.

Immune system modulators work in several ways:

• stimulate the immune system to attack and destroy cancer cells
• directly kills and stops the growth of cancer cells
• blocks growth of new blood vessels that supply the cancer cells

Immune system modulators are:

• used to treat myeloma, chronic myeloid leukaemia (CML), myelodysplatic neoplasms (MDS), myelofibrosis
• are oral tablets

Side effects of immune system modulators:

• fever
• chills
• weakness
• dizziness
• nausea or vomiting
• muscle or joint aches
• fatigue
• headache
• blood clots
• nerve problems which may cause pain, numbness, tingling, swelling, or muscle weakness
• birth defects, if used during pregnancy

CAR T-cell therapy is a treatment that re-engineers a patient’s T-cells (T cells are part of the immune system that help kill foreign cells) with synthetic proteins. These proteins are called chimeric antigen receptors (CARs). CARs help T cells attach to specific proteins so they can recognise and kill cancer cells.

CAR T-cell therapy:

• involves taking T cells from a patient’s blood through an Apheresis machine
• T-cells are taken to the laboratory modified and engineered to find and kill the cancer cells, multiplied and then frozen
• chemotherapy is given to the patient to reduce the number of normal T-cells to make room for the CAR T-cells
• the frozen CAR T-cells are reinfused where they multiply in number and ‘attack’ the cancer cells
• is currently approved for use in Australia for some types of acute lymphoblastic leukaemia (ALL), some types of lymphoma and myeloma
• is engineered to recognise particular proteins on the surface of specific cells
• is not indicated for all blood cancers as appropriate targets have not yet been identified
• new targets are being investigated in national and international clinical trials

Side effects of CAR T-cell Therapy:

• fevers/chills
• rapid heart rate
• low blood pressure
• fatigue
• nausea/vomiting/diarrhoea
• cough
• Cytokine Release Syndrome

Additional resources

• What is CAR T Cell Therapy? Video from the Peter MacCallum Cancer Centre
• Leukaemia Foundation CAR T Cell Therapy Factsheet

Cancer growth inhibitors are a type of targeted therapy. They block signals to cancer cells to stop them from growing or surviving. There a few types of cancer growth inhibitors:

B-cell leukaemia/lymphoma-2 (BCL2) inhibitors:

An example of a BCL2 inhibitor is venetoclax

• are used to treat chronic lymphocytic leukaemia (CLL), acute myeloid leukaemia (AML)
• BCL2 is a type of protein some cancer cells make
• BCL2 inhibitors block the protein and the cancer cells die
• are oral tablets

Bruton’s tyrosine kinase inhibitors (BTKi’s):

Some BTKI’s are ibrutinib, acalabrutinib, zanubrutinib

• Bruton’s tyrosine kinase (BTK) protein is essential to the growth of B-cells
• are used to treat chronic lymphocytic leukaemia (CLL), some lymphomas
• BTKi’s block the B-cell receptor (BCR) on cancer cells
• When this receptor is blocked the cancer cells die
• are oral tablets

Phosphoinositide 3-kinase (PI3K) inhibitors:

Idelalisib is an example of a PI3K inhibitor

• phosphoinositide 3-kinase is a protein important to the growth and survival of cells
• PI3K inhibitors block the PI3K protein in some cancer cells and slow down growth
• are oral tablets
• are used to treat chronic lymphocytic leukaemia (CLL) and some lymphomas
• must be taken as prescribed, doses should not be missed

Tyrosine kinase inhibitors (TKIs):

Examples of TKIs are imatinib, nilotimib, dasatinib, asciminib, ponatinib, gilteritinib and ruxolitinib

• block the tyrosine kinases (proteins) that the cells use to signal each other to grow. This stops the cancer cells growing
• are used to treat chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), myelofibrosis
• there are several different TKIs that all work slightly differently
• are all oral tablets
• must be taken as prescribed, doses should not be missed
• usually work within 3-6 months
• may be switched if the first type doesn’t work well enough or has major side effects

Side effects from targeted therapies tend to be different to chemo side effects. If you’re having more than one type of drug, you may have a few different side effects at different times.

Side effects of cancer growth inhibitors may include:

• diarrhoea
• nausea
• constipation
• fatigue
• shortness of breath
• feet and hand swelling
• body aches and pains
• headache
• stomach pain
• rash
• low blood counts
• infection
• an irregular heart rhythm called atrial fibrillation
• high blood pressure
• bleeding
• hair thinning

There are many types and can be referred to as a targeted therapy or an immunotherapy. For further information on monoclonal antibodies refer to the Immunotherapy information.

Bortezomib, ixazomib, carfilzomib are examples of proteasome inhibitors.

• Proteasomes break down excess proteins in cells, cells need them to grow and develop
• Proteasome inhibitors work by blocking the proteasomes so that proteins build up in the cell and the cell dies
• is given either subcutaneously (under the skin), intravenously (IV) or orally
• used to treat myeloma

Side effects of proteasome inhibitors may include:

• nausea
• vomiting
• diarrhoea
• constipation
• back pain
• shortness of breath
• fatigue
• Low blood counts
• numbness or tingling hands and feet
• hand and feet swelling