lintuzumab-Ac225 + venetoclax + azacitidine

A three-drug combination consisting of: - **lintuzumab-Ac225**: a radioimmunoconjugate consisting of a humanized monoclonal antibody (lintuzumab) targeting CD33, conjugated with the alpha-emitting radioisotope actinium-225. It delivers targeted cytotoxic alpha radiation specifically to CD33-expressing myeloid leukemia cells, resulting in DNA damage and cell death[1][3][7]. - **venetoclax**: a small molecule inhibitor of BCL-2, promoting apoptosis by blocking anti-apoptotic signals in hematologic malignancy cells[2][10]. - **azacitidine**: a hypomethylating nucleoside analog that inhibits DNA methyltransferase, causing DNA hypomethylation and reactivation of tumor suppressor genes, leading to cytotoxicity in abnormal myeloid cells[2][10]. The combination is under investigation for the treatment of **acute myeloid leukemia (AML)**—particularly relapsed/refractory AML or AML with adverse genetic features (e.g., FLT3 or MLL abnormalities). The rationale is synergistic antileukemic efficacy: lintuzumab-Ac225 induces DNA damage via targeted alpha radiation; venetoclax drives apoptosis by BCL-2 inhibition; azacitidine induces epigenetic modulation and cytotoxicity. Preclinical and early clinical work aim to determine whether adding CD33-directed radiopharmaceutical to standard-of-care venetoclax + azacitidine can improve remission rates and durability in AML[1][2][3][10].

Brand names

Actimab-A

Other names

Actinium-225-lintuzumabActinium225-lintuzumabActinium 225-lintuzumab225Ac-HuM-195Ac-225-LintuzumabAc225-LintuzumabAc 225-LintuzumabActimab-MActimab-MDSABT-199ABT199ABT 199