ROCHESTER, Minn. — Research from Mayo Clinic is helping refine how multiple myeloma is diagnosed and treated, with findings that support more personalized therapies and identify promising immunotherapy strategies for aggressive forms of the disease.

The research led by Sikander Ailawadhi, M.D., Shaji Kumar, M.D., Akhilesh Pandey, M.D., Ph.D., and Richard Kandasamy, Ph.D. in the Mayo Clinic Comprehensive Cancer Center, focuses on tailoring treatment based on disease biology and improving outcomes for patients living longer with the cancer.

Treating multiple myeloma as a chronic disease

Multiple myeloma, a blood cancer that affects plasma cells in the bone marrow, can cause abnormal proteins to accumulate and damage organs. At Mayo Clinic, patients with multiple myeloma receive tailored treatment that varies from person to person based on how the disease develops and progresses.

Care strategies continue to evolve, including immunotherapy and clinical trials that study the most effective order to use available treatments. One approach uses monoclonal antibodies given in sequence to better target cancer cells and improve outcomes for patients whose disease has returned.

"We take into account the risks, but also what the patients' wants, needs and aspirations are, and make a decision about treatment that brings all this together," says Dr. Ailawadhi, a hematologist and oncologist. "Much has been learned about the best use of novel treatments such as CAR-T and other immunotherapy approaches."

New immunotherapy strategies show promise

In one area of research, Dr. Kumar, a hematologist, and colleagues published a study in the New England Journal of Medicine showing that an off-the-shelf dual-antibody immunotherapy can produce deep and durable responses in extramedullary multiple myeloma, a form of the disease with historically limited treatment options.

"We are seeing powerful responses in a disease that historically has resisted every therapy," says Dr. Kumar.

The approach uses two engineered antibodies to engage T cells through separate immune pathways, directing an immune response against myeloma cells. The treatment is administered in a standard infusion setting, in contrast to more complex cell therapies.

In early results, a majority of patients responded to the treatment, and many achieved no detectable disease, suggesting a potential new option for patients with resistant disease.

Seeing what standard tests miss

Understanding the full genetic profile of multiple myeloma remains a key challenge in care.

Dr. Pandey, a clinical pathologist in Laboratory Medicine and Pathology, and Dr. Kandasamy, an associate consultant in Immunology and Hematology, are collaborating with other researchers to study a potential new approach to defining the disease. Multiple myeloma is driven by changes in chromosomes that affect prognosis and treatment decisions. Standard testing uses fluorescence in situ hybridization, or FISH, which looks for specific known changes but may not capture the full picture.

A newer method, Genomic Proximity Mapping (GPM), analyzes a patient's entire genome. It can identify structural changes, gains or losses of genetic material and complex rearrangements, including high-risk features. In early studies, GPM confirmed results from standard testing and identified additional clinically important changes.

"This approach could improve risk assessment and help doctors choose treatments that are better tailored to each individual," says Dr. Pandey.

Researchers are now studying GPM testing in larger patient groups and exploring its use in other cancers.

“Beyond multiple myeloma, GPM can identify complex and hidden genetic changes. This means it could be useful across many types of cancer and help give a clearer picture of each person’s disease,” says Dr. Kandasamy.

Looking ahead toward precision care

As multiple myeloma care continues to evolve, new therapies will expand options for resistant disease and advances in testing will help guide treatment decisions. Comprehensive tools such as Genomic Proximity Mapping (GPM) may further refine risk assessment and support earlier, more precise care for patients.

Other clinical trials are evaluating the benefits of earlier use of immunotherapies in treatment and improved supportive care.

While multiple myeloma is considered treatable but not curable, these developments may help extend survival and improve quality of life, with a growing subset of patients achieving long-term remission.

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Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

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