Mayo Clinic researchers find new hope for toughest myeloma through off-the-shelf immunotherapy

ROCHESTER, Minn. — A new Mayo Clinic study published in the New England Journal of Medicine has uncovered that an off-the-shelf, dual-antibody therapy can generate deep and durable responses in extramedullary multiple myeloma — one of the most aggressive and treatment-resistant forms of the disease. 

"We are seeing powerful responses in a disease that historically has resisted every therapy," says Shaji Kumar, M.D., a Mayo Clinic Comprehensive Cancer Center hematologist and senior author of the study. "By recruiting T cells in two distinct ways at once, this dual-target antibody strategy can generate responses in patients who have had very few effective options." 

The approach combines two engineered antibodies, talquetamab and teclistamab, that simultaneously engage T cells and force them to attack myeloma cells through two separate immune pathways. Unlike CAR-T cell therapy, which requires custom manufacturing, this regimen is delivered as a standard infusion-center injection. 

In a trial involving 90 patients, 79% responded to treatment, and 54% achieved no detectable disease by imaging or blood testing. Among responders, nearly two-thirds maintained disease control at one year, a striking improvement for a subtype that typically carries a months-long prognosis. 

This is the first large, prospective study defined specifically by PET/MRI scan and focused exclusively on true extramedullary myeloma, not a mix of para- and extramedullary disease. Serious side effects were common. Infection was one serious side effect and underscores the importance of comprehensive supportive care alongside immunotherapy. 

The next big questions are whether this dual-target strategy can be moved earlier in the disease course, how safety can be optimized further through infection monitoring and prevention, and whether similar "two-locks, one-key" immune designs can be applied to other hard-to-treat cancers. 

For a complete list of authors, disclosures and funding, review the study. 

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