Understanding harder-to-treat myeloma

Myeloma is a complex and individual cancer. While many people respond well to treatment and have long periods of remission or plateau, others may find that their myeloma returns sooner than expected or is less responsive to treatment. This is sometimes described as harder-to-treat myeloma.

In this month’s blog, we explore some of the questions you ask our Myeloma Infoline team about myeloma that is harder to treat.

What is harder-to-treat myeloma?

Harder-to-treat myeloma is an informal term that some people use to describe myeloma that is more difficult to treat and control. Healthcare professionals do not usually use it as a formal diagnosis. Instead, they may talk about:

• Early relapse – when myeloma returns sooner than expected after treatment.
• Refractory myeloma – myeloma that is not responding, or no longer responding, to a particular treatment.
• High-risk myeloma – myeloma with certain features including some genetic changes that are linked with a higher chance of relapse or progression.

Myeloma that is harder to treat can still be treated successfully. There are many treatment options available and your healthcare team will consider these based on how the myeloma behaves and responds over time.

Why might myeloma be harder to treat?

Several factors can influence how myeloma behaves. These can include:

• How advanced the myeloma is at diagnosis.
• How quickly the myeloma is progressing.
• How well the myeloma responds to treatment.
• Certain genetic or chromosomal changes in the myeloma cells.
• A person’s overall health and any complications caused by myeloma, such as kidney problems.

What is refractory myeloma?

Refractory myeloma means that the myeloma is not responding or is no longer responding to a particular treatment. Whilst most people with myeloma become refractory to some treatments eventually, others become refractory much quicker, making the myeloma harder to treat.

Some people may also hear the term ‘triple-class refractory myeloma’. This means the myeloma is no longer responding to the three main classes of myeloma treatment:

• Immunomodulatory drugs (IMiDS) such as lenalidomide (Revlimid®)
• Proteasome inhibitors such as bortezomib (Velcade®)
• Anti-CD38 antibodies such as daratumumab (Darzalex®)

Although triple-class refractory myeloma can be more challenging to treat, there may still be treatment options available. These usually include newer therapies, different drug combinations and opportunities to participate in clinical trials. Your healthcare team can discuss which options may be appropriate for your individual circumstances.

What is high-risk myeloma?

High-risk myeloma is a term used when myeloma has certain characteristics that are associated with a higher chance of relapse or progression.

One of the ways healthcare teams can identify high-risk myeloma is through genetic testing of myeloma cells. These look for changes in the DNA and chromosomes of the cells.

Healthcare teams also consider other information including blood test results, scans, bone marrow samples and how the myeloma is responding to treatment.

Being told you have high-risk myeloma can feel overwhelming. However, treatments can still be effective. Many people with high-risk myeloma respond well to treatment and achieve periods of remission, although these may sometimes be shorter than in those with standard-risk myeloma.

Your healthcare team can discuss any concerns with you and our Myeloma Information Specialists can also offer support – get in touch on 0800 980 3332 (UK) or use our Ask the Nurse email service.

How do genetic tests help?

Myeloma cells develop changes in their DNA and chromosomes that make them behave differently from healthy cells. Not all myeloma cells share the same genetic changes, which is why myeloma can behave differently in one person compared to another.

Tests such as FISH (Fluorescence in-situ hybridisation) and karyotyping can help identify some of these changes. You can read more about these tests in our Ask The Nurse blog about Chromosome testing and FISH. These tests are often carried out at diagnosis and sometimes at relapse.

The results can help your healthcare team better understand how the myeloma is likely to behave and can support treatment planning and monitoring.

You may hear your healthcare team refer to standard-risk or high-risk myeloma based on the results of these tests. It’s important to remember that these risk categories describe patterns seen across groups of people and cannot predict exactly what will happen to an individual.

The type and extent of genetic testing available may vary depending on local protocols and capacity. Your healthcare team can tell you if genetic testing is available and appropriate for you. If you’re not sure what tests you have had, or whether genetic testing has been carried out, speak to your healthcare team who can explain this and discuss any results with you.

How might treatment differ?

Identifying high-risk or harder-to-treat myeloma allows healthcare teams to make informed decisions about your treatment plan. Depending on your personal circumstances you may be recommended a different or more intensive treatment approach. The aim is to achieve the longest period of remission while maintaining quality of life.

Your healthcare team will consider many factors when making recommendations, including your age, fitness, general health, treatment goals and personal preferences. They may also discuss whether a clinical trial could be suitable for you.

Can genetic risk change over time?

Myeloma cells can change over time. This means that new genetic changes can sometimes develop, affecting the way the myeloma behaves. For this reason, your healthcare team may repeat tests at relapse to gain a better understanding of how the myeloma has changed and to help guide future treatment decisions.

Myeloma is very complex and no two people’s experiences are the same. Terms such as high-risk, refractory or harder-to-treat myeloma can sound worrying, but they do not determine exactly what will happen to an individual.

Treatments continue to improve and healthcare teams use a range of information to help recommend the most appropriate treatment options for you and your individual circumstances.

If you have any further questions or need support, contact us through the Myeloma UK Infoline at 0800 980 3332 (UK) or use our Ask the Nurse email service