vadastuximab talirine + azacitidine

Vadastuximab talirine + azacitidine is an investigational combination regimen for the treatment of hematologic malignancies, primarily *acute myeloid leukemia (AML)* and *myelodysplastic syndrome (MDS)*. Vadastuximab talirine is a CD33-directed antibody-drug conjugate (ADC) consisting of a humanized anti-CD33 monoclonal antibody conjugated via a cleavable dipeptide linker to a pyrrolobenzodiazepine (PBD) dimer payload, a highly potent DNA-crosslinking cytotoxic agent. The antibody targets CD33-expressing cells, leading to internalization and intracellular release of the PBD toxin, causing DNA crosslinking, cell cycle arrest, and apoptosis specifically in CD33-positive cells. *Azacitidine* is a hypomethylating agent (HMA) that induces DNA hypomethylation, promoting cell differentiation and apoptosis in abnormal hematopoietic cells. Clinical trials in elderly or unfit AML and high-risk MDS have investigated this combination, finding increased remissions but also greater myelosuppression compared to HMA alone.