siremadlin + venetoclax + azacitidine

Siremadlin + venetoclax + azacitidine is a **triple-combination therapy** under clinical investigation for the treatment of **acute myeloid leukemia (AML)** in adults who are ineligible for intensive chemotherapy. **Siremadlin** is a selective oral small-molecule inhibitor of MDM2, which increases p53 activity leading to apoptosis of cancer cells. **Venetoclax** is a selective BCL-2 inhibitor that induces apoptosis in cancer cells dependent on BCL-2 for survival. **Azacitidine** is a hypomethylating agent that incorporates into DNA and RNA, causing cytotoxicity in abnormal hematopoietic cells and restoring normal gene expression through DNA demethylation. The goal of combining these agents is to enhance anti-leukemic activity and clinical response, particularly in patients with a suboptimal response to first-line venetoclax + azacitidine, or those with high-risk AML clinical features who are ineligible for standard chemotherapy[1][2][6][8].

Brand names

Vidaza (injectable)Onureg (oral)

Other names

HDM201 + ABT-199 + azacitidineSiremadlin + venetoclax + azacitidine