pevonedistat + azacitidine

Pevonedistat + azacitidine is a combination therapy under clinical investigation for hematologic malignancies, principally higher-risk myelodysplastic syndromes (HR-MDS), chronic myelomonocytic leukemia (CMML), and low-blast acute myeloid leukemia (LB-AML). Pevonedistat is a small molecule inhibitor of NEDD8-activating enzyme (NAE), which disrupts the NEDD8/ubiquitin-proteasome pathway, inhibiting degradation of proteins vital for tumor growth and survival. Azacitidine is a DNA methyltransferase inhibitor and hypomethylating agent that promotes DNA hypomethylation and cytotoxicity in abnormal hematopoietic cells. Combined, this regimen shows increased rates of complete remission, improved event-free and overall survival, and a safety profile comparable to azacitidine alone, with reduced myelosuppression compared to other azacitidine-based combinations[1][2][5][9].