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**melflufen + dexamethasone + bortezomib** is a three-drug combination therapy investigated for the treatment of relapsed/refractory multiple myeloma. - **melflufen** (melphalan flufenamide) is a first-in-class, alkylating peptide-drug conjugate that exploits increased aminopeptidase activity in myeloma cells to deliver cytotoxic alkylating agents directly inside the malignant cells. - **dexamethasone** is a synthetic glucocorticoid corticosteroid with anti-inflammatory and immunosuppressive effects, often used to reduce inflammation and adverse reactions in cancer regimens. - **bortezomib** is a small molecule proteasome inhibitor that disrupts protein breakdown, leading to apoptosis in myeloma cells. This combination works through synergistic mechanisms: melflufen introduces DNA damage via alkylation; bortezomib inhibits proteasome-dependent cellular cleanup processes; dexamethasone enhances cytotoxicity and helps control side effects. The regimen has shown high overall response rates (ORR up to 78%) and durable responses in clinical studies for multiple myeloma, with primary toxicities being hematological (thrombocytopenia, neutropenia), and is considered manageable with standard supportive care[1][2][3][5].
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