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XmAb24306 + daratumumab is a combination investigational therapy for relapsed or refractory multiple myeloma. **XmAb24306** (also called efbalropendekin alfa or RG6323) is a recombinant, half-life-extended IL-15/IL-15 receptor alpha heterodimer Fc fusion protein engineered to stimulate immune effector cells, especially natural killer (NK) cells, enhancing both their direct cytotoxic and antibody-dependent cellular cytotoxicity (ADCC). **Daratumumab** is a human monoclonal antibody targeting CD38, inducing ADCC and direct cytotoxicity against multiple myeloma cells, but it can also cause depletion (fratricide) of CD38-positive NK cells. Preclinical data show that XmAb24306, when combined with daratumumab, further boosts NK cell-mediated cytotoxicity against myeloma cells, even at low effector-to-target ratios, despite increased NK cell fratricide. This combination was studied in Phase 1 clinical trials for safety and pharmacokinetics in relapsed/refractory multiple myeloma patients.
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