azacytidine + pomalidomide

Azacytidine + pomalidomide is an investigational combination therapy consisting of two small molecule drugs with distinct but potentially complementary mechanisms of action. Azacytidine is a pyrimidine nucleoside analogue and hypomethylating agent that incorporates into DNA and RNA, inhibiting DNA methyltransferase, disrupting abnormal gene expression, and inducing cytotoxicity in malignant cells. Pomalidomide is an immunomodulatory agent that inhibits tumor cell proliferation, induces apoptosis, enhances T cell and natural killer (NK) cell-mediated immunity, inhibits pro-inflammatory cytokines such as TNF-alpha and IL-6, and targets the protein cereblon to inhibit ubiquitin ligase activity. This combination has been explored primarily in relapsed or refractory multiple myeloma (RRMM), aiming to overcome drug resistance by leveraging both epigenetic modulation (azacytidine) and immune activation/anti-tumor effects (pomalidomide). Clinical studies have investigated similar regimens combining azacytidine with other immunomodulatory drugs for RRMM[2][7].