What Does a High-Risk Multiple Myeloma Diagnosis Mean?

“Am I high risk?” It's one of the questions patient navigators at the Multiple Myeloma Research Foundation® (MMRF®) hear most often from patients newly diagnosed with multiple myeloma - a cancer that forms in plasma cells, a type of white blood cell found in bone marrow.

Understanding what risk means, and how it's measured, can help patients feel more empowered as they work with their care team to build a treatment plan.

In myeloma, “risk” describes how active or aggressive the disease might be and how it's likely to respond to treatment. High-risk myeloma may not respond as well, or as deeply, to standard treatment, compared with standard-risk disease.

That doesn't mean a diagnosis of high-risk myeloma leaves patients without options, Grace Allison, RN, BSN, OCN, LIONs, a patient navigator at the MMRF, explained in an educational video. Instead, knowing a risk level gives patients and their doctors more information to shape the plan that fits them best.

What determines multiple myeloma risk?

Risk level is typically determined by information gathered from a bone marrow biopsy and bloodwork, which can reveal specific genetic changes, known as chromosomal abnormalities, inside myeloma cells. Certain chromosomal abnormalities in myeloma tumor cells are linked to a higher-risk form of the disease. These genetic markers are usually identified through specialized lab testing performed on the bone marrow sample collected at diagnosis, and sometimes again if the disease changes course.

This genetic testing is typically done through a lab technique commonly known as FISH testing (fluorescence in situ hybridization), which allows pathologists to look directly at myeloma cells and flag specific chromosomal changes that have been associated with more aggressive disease.

Two additional disease features can also signal higher risk. One is plasma cell leukemia, a condition in which high levels of plasma cells are found circulating in the bloodstream rather than staying contained in the bone marrow. The other is extramedullary disease, which occurs when myeloma cells leave the bone marrow entirely and form tumors in soft tissue or organs elsewhere in the body. Both findings give a care team important information about how the disease is behaving.

How can a patient’s risk guide treatment decisions?

A high-risk designation doesn't mean a patient has run out of treatment options. Instead, it can help a care team recommend an approach tailored to more aggressive disease, such as certain combination therapies or clinical trials designed specifically for patients with high-risk myeloma.

Because risk influences how a care team thinks about pacing and intensity of treatment, patients who understand their own risk status are often better equipped to ask informed questions and participate in decisions about their care.

Allison recommended that patients bring a short list of questions to their next appointment, which can include:

• Does my biopsy show any high-risk features?
• How does my risk level influence my treatment plan?
• Should I consider a clinical trial?
• Would more frequent monitoring make sense for me?

These conversations can help clarify not just a diagnosis, but a path forward.

How is every patient's risk profile different?

It's worth remembering that no two patients with high-risk myeloma look exactly alike, and specialists who regularly treat high-risk disease will typically have experience with a range of treatment options that work for these patients. Risk level is one piece of a much larger picture that includes overall health, disease stage and how a patient responds to initial treatment.

It's also not necessarily fixed at diagnosis; some patients' disease can change behavior over time, which is one reason ongoing monitoring and follow-up testing matter even after a treatment plan is underway.

Whatever a person's risk level, having accurate information is one of the most concrete ways to feel more in control of a myeloma diagnosis, Allison said, and the MMRF's navigators are available to help patients and caregivers find that information and the support to act on it.

For more information, reach out to the MMRF Patient Navigation Center. Patient Navigators are available to share resources and information and provide guidance to help patients and caregivers navigate their myeloma journey: MMRF Patient Navigation Center | Myeloma Patient Support.

Reference

1. Multiple Myeloma Research Foundation. What Is High-Risk Multiple Myeloma? Understanding Your Multiple Myeloma Risk Level. YouTube. Published June 26, 2026. Accessed July 22, 2026.