Practical aspects of the use of ventoclax in combination with azacitidine for the treatment of newly diagnosed acute myeloid leukaemia in patients ineligible for intensive chemotherapy

Abstract

The aim of treating elderly patients with acute myeloid leukaemia (AML) ineligible for intensive chemotherapy is to extend survival, but treatment results are often unsatisfactory. Therapy with venetoclax combined with azacitidine allowed remission in two-thirds of patients and significantly prolong the median overall survival. The treatment is increasingly used in clinical practice and establishes a new medical standard. The use of venetoclax in treating AML requires knowledge of drug use rules and their individualization. This review summarizes critical elements of the clinical practice of venetoclax use in combination with azacitidine regarding the dosing regimen, management of cytopenias during therapy and treatment adjustments to prevent drug-to-drug interactions. Treatment with venetoclax can cause the risk of tumor lysis syndrome (TLS), and therefore step-wise dose ramp-up is required with the prophylaxis of TLS and reduction in leucocyte count. Cytopenias that occur during the therapy affect most of the patients; nevertheless, it is not recommended to modify the treatment until the remission of the disease. In haematologic toxicity after disease remission, it is recommended to delay the next cycle and shorten the treatment while maintaining the dose. Knowledge about venetoclax drug-to-drug interactions is necessary for an efficacious and safe therapy. It is essential to reconsider the rationale behind using some agents, e.g., azole derivatives commonly used in the prophylaxis of invasive fungal infections, as well as to be aware of the rules of venetoclax dosing. Detailed knowledge of the above aspects of therapy is essential to ensure the continuity, safety, and efficacy of venetoclax with azacitidine.