A Mayo Clinic study published in the New England Journal of Medicine reports that an off-the-shelf, dual-antibody therapy can produce 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,” said Shaji Kumar, M.D., a hematologist at the Mayo Clinic Comprehensive Cancer Center and senior author of the study. “By recruiting T cells in two distinct ways at once, this dual-target antibody strategy can benefit patients who have had very few effective options.”
The therapy combines two engineered antibodies, talquetamab and teclistamab, which simultaneously engage T cells to attack myeloma cells through separate immune pathways. Unlike CAR-T cell therapy, which requires customized manufacturing, this treatment is delivered via a standard infusion-center injection.
In a trial of 90 patients, 79% responded to treatment, and 54% achieved no detectable disease based on imaging or blood tests. Among responders, nearly two-thirds maintained disease control at one year—a significant improvement for a subtype typically associated with only months-long survival.
This study is the first large, prospective trial to focus exclusively on true extramedullary myeloma, defined by PET/MRI scans, rather than a mix of para- and extramedullary disease. Serious side effects were common, with infections highlighting the need for careful supportive care alongside immunotherapy.
Researchers now aim to determine whether the dual-target strategy can be applied earlier in the disease, how safety can be further improved through infection monitoring and prevention, and whether similar “two-locks, one-key” immune designs could benefit other hard-to-treat cancers.
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