New Guidelines Define High-Risk Myeloma with Genetics in Mind

For people living with multiple myeloma, understanding their risk status helps guide care and set realistic expectations. A recent update from the International Myeloma Society (IMS) and the International Myeloma Working Group (IMWG) provides a new definition based on the use of modern genetic tools to better identify which patients fall into this category.

High-risk multiple myeloma is now defined using a set of genetic and blood test criteria that identify patients with a poorer outlook despite current treatments.

The key genetics that define high-risk

According to the new guidelines, a patient is considered to have high-risk multiple myeloma if they have at least one of the following:

• Deletion 17p [del(17p)]: This is the loss of part of chromosome 17 and must be present in 20% or more of the myeloma cells. It leads to loss of the TP53 gene, which normally regulates cell growth. And TP53 mutation: Having a mutation in this gene also signals aggressive disease, and it can make the body prone to have other types of cancer as well. 
• Translocations: These include t(4;14), t(14;16), or t(14;20), but only if they occur alongside changes in chromosome 1 such as: 1q gain or amplification which involves an extra copy of part of chromosome 1.
• Deletion of 1p32, or deletion of 1p32 plus 1q gain.
• High levels of β2-microglobulin (≥5.5 mg/L) without kidney issues: This blood marker reflects disease burden or aggressive disease when not the elevation is not due to kidney dysfunction.

These changes are important because they are tied to shorter survival, even with modern therapies. They help identify patients who may need closer monitoring or newer approaches to treatment.

Why past staging systems no longer capture the full picture

Earlier tools like the Revised International Staging System (R-ISS) focused on blood levels of markers like albumin and β2-microglobulin, and on chromosome changes. However, they often grouped patients too broadly. For example, many patients labeled “intermediate-risk” by R-ISS still experienced very different outcomes.

The new definition focuses more on myeloma's biology. About 20% of newly diagnosed patients have high-risk features. Recognizing this early can lead to different treatment decisions.

Next steps for myeloma patients

If you're diagnosed with multiple myeloma, your care team may run genetic and molecular tests to check for these high-risk features. If any are present, your treatment plan might change. You may:

• Be monitored more closely
• Be recommended for newer or more aggressive treatment options
• Be considered for clinical trials aimed at high-risk patients

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Looking Ahead: Risk Evaluation May Change Over Time

The new definition also suggests that risk status should be reassessed at relapse, not just at diagnosis. Some patients develop new high-risk features later in their disease course, and this may require adjusting treatment.

In the future, even more refined tools may emerge. Experts are already looking into how newer technologies like gene expression profiling and circulating tumor cell detection could further improve risk assessment.

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Source: 

• International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma