Ask The Nurse // 6th April 2021
One of the earliest drugs used to treat myeloma was the immunomodulatory drug thalidomide. Today, there are three immunomodulatory drugs used as myeloma treatment: thalidomide, lenalidomide (Revlimid®) and pomalidomide (Imnovid®). Most myeloma patients will receive at least one of these drugs, so in this month’s blog, we answer some of the questions we get asked about immunomodulatory drugs.
What are immunomodulatory drugs?
Immunomodulatory drugs (sometimes known as IMiDs) are a family of drugs that work by stimulating or suppressing the immune system to treat disease.
The immunomodulatory drugs used for myeloma also directly attack and kill myeloma cells.
They have been shown to do this in a few different ways:
- By altering the production of chemical messages involved in the growth and survival of the myeloma cells
- By blocking the growth of new blood vessels that supply the myeloma cells with oxygen and nutrition
What are the common side effects of immunomodulatory drugs?
Like all drugs, immunomodulatory drugs can cause several side effects which can vary from patient to patient.
Side effects associated with immunomodulatory drugs include:
Immunomodulatory drugs can cause diarrhoea, constipation, nausea, heartburn or indigestion.
Often, maintaining a good fluid intake and a balanced diet can help manage gastrointestinal side effects. You can also speak to your healthcare team who may prescribe specific treatment to help with your gastrointestinal issues.
A particular condition called bile acid malabsorption (BAM) has been identified as the cause of diarrhoea in some patients taking lenalidomide. This is where patients do not absorb bile acids properly from their intestine. It can be treated by making some dietary changes, such as making sure that fat does not make up more than 20% of the diet, but often other treatment, such as a drug called colesevelam, is also needed.
Immunomodulatory drugs can increase the risk of blood clots Therefore, you may be prescribed an anticoagulant (anti-clotting) drug such as aspirin, low-dose heparin or warfarin to prevent or treat blood clots.
You must tell your doctor or nurse if you notice any red, swollen or painful areas, particularly in your calf, that is warm to the touch. Any new episodes of shortness of breath and/or chest pains must be reported immediately.
Peripheral neuropathy is damage to the nerves in the hands, feet, arms or legs. This can cause numbness, tingling, increased sensitivity and pain.
For most patients, these symptoms will improve or disappear after the dose and/or frequency of administration of the immunomodulatory drug is reduced. However, sometimes, treatment may need to be temporarily stopped or discontinued and other options discussed.
You can read our Treatment Guides for thalidomide, lenalidomide and pomalidomide to find out more about the side effects of these drugs. It is important to report any side effects to your doctor or nurse so they can be treated or managed promptly.
How are immunomodulatory drugs used to treat myeloma?
Thalidomide is typically used to treat newly diagnosed patients. It is used in combination with bortezomib (Velcade®) and dexamethasone. This combination is often called VTD.
Lenalidomide is approved for use in several different ways. It is most commonly used in combination with dexamethasone, in combination with ixazomib and dexamethasone (Ninlaro®), or as a maintenance treatment following high-dose therapy and stem cell transplantation. Most recently it was approved for use with carfilzomib (Krypolis®) and dexamethasone at first relapse (second line).
Pomalidomide is mainly used to treat relapsed and/or refractory myeloma in combination with dexamethasone. Last year, it was approved for use in combination with isatuximab (Sarclisa®) and dexamethasone at third relapse (fourth line).
An immunomodulatory drug successfully treated my myeloma before, will a different one work just as well?
Myeloma is a very individual and complex cancer and there is no clear way to predict who will respond well to individual treatments. How well you respond to treatment will depend on a number of factors such as the nature of your myeloma, your general health and any other health issues This can change with subsequent relapses. Therefore, having a good response to thalidomide doesn’t guarantee a good response to lenalidomide or pomalidomide.
However, this also means patients who are refractory (do not respond to) to one immunomodulatory drug aren’t refractory to all immunomodulatory drugs. For example, research has shown patients refractory to lenalidomide can respond well to pomalidomide.
Are the newer immunomodulatory drugs better?
Directly comparing the safety and efficacy of thalidomide, lenalidomide and pomalidomide is challenging. This is because the drugs are used in combination with several different drugs at different stages of the myeloma treatment pathway. For example, pomalidomide has only really been tested for the treatment of relapsed and refractory myeloma. As a result, there is limited data directly comparing the effectiveness of the drugs.
Nevertheless, research shows that lenalidomide and pomalidomide are less likely to cause peripheral neuropathy than thalidomide.
Are there any other immunomodulatory drugs being developed for myeloma?
The manufacturers of thalidomide, lenalidomide and pomalidomide are working to develop new types of immunomodulatory drugs. There are two derivatives, iberdomide (CC-220) and CC-92480, in clinical trials for the treatment of myeloma. It is hoped that these drugs will effectively treat patients who are refractory to lenalidomide.
If you have any questions about myeloma treatments, you can get in touch with us through the Infoline (0800 980 3332 (UK) or 1800 937 773 (Ireland)) or the Ask The Nurse email service.
The Myeloma Information Specialists