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A triple combination therapy consisting of **talquetamab** (a bispecific T-cell engager targeting both GPRC5D on myeloma cells and CD3 on T-cells), **daratumumab** (a monoclonal antibody targeting CD38 on plasma cells), and **pomalidomide** (an immunomodulatory agent and thalidomide analogue). This regimen has demonstrated deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma, including those previously exposed to CAR T-cell and bispecific antibody therapies. Talquetamab activates T-cells against GPRC5D-expressing myeloma cells, daratumumab targets and depletes CD38-positive plasma cells while modulating immune cell subsets, and pomalidomide stimulates T-cell and NK cell activity while directly cytotoxic to myeloma cells. The combination leads to amplified immune activation, increased T-cell activity and granzyme B secretion, improved CD8 and NK cell recovery, and reduced regulatory T-cell–mediated immunosuppression[1][2][3][4][5][6].
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