5-azacitidine + gemtuzumab ozogamicin

5-azacitidine + gemtuzumab ozogamicin is a combination regimen studied for relapsed or refractory acute myeloid leukemia (AML). 5-azacitidine is a hypomethylating cytidine analog that inhibits DNA methyltransferase, leading to DNA hypomethylation and gene re-expression; it can increase CD33 expression and modulate signaling proteins (e.g., Syk and SHP-1) that may enhance gemtuzumab ozogamicin activity.[5] Gemtuzumab ozogamicin is a CD33-directed antibody–drug conjugate (ADC) (antibody hP67.6) with a N-acetyl gamma calicheamicin dimethyl hydrazide payload linked via a hydrolytically cleaved hydrazone linker; it binds CD33 on AML blasts, is internalized, and releases the cytotoxic payload, causing DNA double-strand breaks and apoptosis.[8][10] Phase I/II trials in relapsed/refractory AML evaluated azacitidine followed by gemtuzumab ozogamicin, establishing a tolerated schedule (azacitidine 75 mg/m2 days 1–6; gemtuzumab ozogamicin 6 mg/m2 on days 7 and 21) with CR/CRp of approximately 24% and acceptable safety without observed sinusoidal obstruction syndrome in that study.[3] The combination has also been explored as bridge therapy to allogeneic transplant in R/R AML.[9] A Stanford-led Phase I/II study specifically tested this combination in relapsed AML.[1]

Brand names

Mylotarg

Other names

azacitidine + gemtuzumab ozogamicin5-aza + GOazacitidine + GO