Targeted treatMents

You may have already heard of this type of treatment, as ibrutinib was available in England and Wales for a short period of time, and still remains available in Scotland. Zanubrutinib is another type of BTK inhibitor, which is available in the United Kingdom.

BTK inhibitors target a protein called Bruton’s tyrosine kinase (BTK). This protein is found in the abnormal B-cells that cause WM. BTK inhibitors block the messages the protein sends out, stopping the abnormal cells from dividing, and halting or slowing the growth of your WM.

Ibrutinib and zanubrutinib are taken daily as a tablet. There isn’t a set course for the treatment – you take it for as long as it halts or slows the growth of your WM. This can be several years.

Side effects can include:

• Nausea
• Diarrhoea
• Easy bruising
• Increased risk of bleeding
• Increased blood pressure
• Increased risk of an abnormal heart rhythm (palpitations)

Be sure to tell your healthcare team of any other medication you’re taking as they could interfere with a BTK inhibitor.

You may also hear of other BTK inhibitors, which are under review or going through clinical trials. These have been designed in the hope that they will be more effective and/or have less side effects than ibrutinib and zanubrutinib:

• Acalabrutinib
• Tirabrutinib
• Pirtobrutinib

This group of medicines blocks a chemical called proteasome. Proteasome helps to break down proteins. This is important in lymphoma cells because they produce more proteins than healthy cells. By blocking the proteasome, the cells that cause WM get ‘overloaded’, meaning they can’t work properly and die.

There are currently no proteasome inhibitors available to people with WM on the NHS, but you may hear of the following medicines, which are being studied both in the UK and abroad to see how well they treat people with WM:

• Bortezomib – commonly used in other blood cancers and is given most commonly as a weekly injection under the skin. It is usually well tolerated but can cause a neuropathy, diarrhoea or nausea
• Carfilzomib
• Ixazomib

These medicines help your immune system respond more effectively to lymphoma cells, as well as targeting the lymphoma cells themselves to stop them from dividing. Currently, these aren’t available for people with WM, as clinical trials have shown them to have problematic side effects. However, a newer type of immunomodulator called pomalidomide has shown more promising results in treating people with WM.

T-cells play a big role in your immune system, seeking out and fighting cells causing damage. WM cells use a protein to ‘hide’ from the T-cells so they aren’t attacked. Checkpoint inhibitors target these proteins, helping your T-cells to find and attack the WM cells.

These drugs aren’t available to people with WM, but you may hear of the following medicines which are being studied:

• Nivolumab
• Pembrolizumab

The abnormal cells that cause WM can produce a protein called B-cell lymphoma-2 (BCL-2) which helps the cells live for longer. BCL-2 inhibitors stop this protein from working so that the cells die.

There aren’t any BCL-2 inhibitors available to people with WM at the moment. However, a drug called venetoclax is being trialled in people with B-cell lymphomas, including WM.