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**gemtuzumab ozogamicin + zosuquidar** is an investigational combination therapy for **acute myeloid leukemia (AML)**, especially in relapsed or refractory disease and in elderly patients. Gemtuzumab ozogamicin is an antibody-drug conjugate targeting CD33, delivering the cytotoxic agent calicheamicin to leukemic blasts. Zosuquidar is a third-generation, highly specific inhibitor of the ATP-binding cassette transporter **P-glycoprotein (ABCB1/MDR1)**, which mediates drug efflux and contributes to multi-drug resistance. By inhibiting P-glycoprotein, zosuquidar restores sensitivity to chemotherapeutic agents such as gemtuzumab ozogamicin, enhancing cytotoxicity in AML blasts expressing active P-gp. Clinical studies show that the combination achieves notable overall response rates and improves median survival in P-gp-positive patients, with manageable toxicities.
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