ibrutinib + azacitidine

Ibrutinib + azacitidine is a combination of two small molecule drugs used in investigational regimens for hematologic malignancies, particularly acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS). Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK), which blocks B-cell receptor signaling by forming a covalent bond with the BTK active site, thereby inhibiting downstream pathways critical for malignant cell survival and proliferation. Azacitidine is a hypomethylating agent that inhibits DNA methyltransferase at low doses, leading to DNA hypomethylation and reactivation of silenced genes; at higher doses, it incorporates into RNA and DNA causing cytotoxicity through disruption of nucleic acid metabolism. The combination has been studied in phase 2 trials but has shown limited efficacy in AML patients[1][2][4].