Venetoclax in the treatment of hematological malignancies and solid tumors

Abstract

Venetoclax belongs to the new class of drugs, mechanism of which is based on inhibition of expression of antiapoptotic BCL-2 family proteins. These proteins are key regulators of intrinsic apoptotic pathway and play an important role in pathogenesis of many neoplastic disorders, including hematological malignancies. Results of preclinical and clinical studies revealed the high selectivity of venetoclax with acceptable safety profile, especially in patients with chronic lymphocytic leukemia (CLL). Its high efficacy in eradication of minimal residual disease influences prolongation of patients' overall survival. Venetoclax monotherapy is dedicated to the treatment of high risk patients with relapsed/refractory CLL, with del17p/TP53 mutation after previous failure therapy by BCR signaling inhibitor. It can be also administered in patients without del17p/TP53 mutation, who failed both immunochemotherapy, as well as treatment with an inhibitor of the BCR pathway. In addition, combination of venetoclax with rituximab is indicated as a second line treatment of CLL patients. Recent studies indicated that venetoclax also appears to be effective in the treatment of other hematological diseases, such as acute myeloid leukemia, multiple myeloma, some non-Hodgkin's lymphoma and solid tumors.