Venetoclax Combination Treatment of Acute Myeloid Leukemia in Adolescents and Young Adult Patients

Abstract

Over the past two decades, the prognosis in adolescents and young adults (AYAs) diagnosed with acute myeloid leukemia (AML) has significantly improved. The standard intensive cytotoxic treatment approach for AYAs with AML, consisting of induction chemotherapy with anthracycline/cytarabine combination followed by consolidation chemotherapy or stem cell transplantation, has lately been shifting toward novel targeted therapies, mostly in the fields of clinical trials. One of the most recent advances in treating AML is the combination of the B-cell lymphoma 2 (Bcl-2) inhibitor venetoclax with hypomethylating agents, which has been studied in elderly populations and was approved by the Food and Drug Administration (FDA) for patients over 75 years of age or patients excluded from intensive chemotherapy induction schemas due to comorbidities. Regarding the AYA population, venetoclax combination therapy could be a therapeutic option for patients with refractory/relapsed (R/R) AML, although data from real-world studies are currently limited. Venetoclax is frequently used by AYAs diagnosed with advanced hematologic malignancies, mainly acute lymphoblastic leukemia and myelodysplastic syndromes, as a salvage therapeutic option with considerable efficacy and safety. Herein, we aim to summarize the evidence obtained from clinical trials and observational studies on venetoclax use in AYAs with AML. Based on the available evidence, venetoclax is a safe and effective therapeutic option for R/R AML AYA patients. However, further research in larger cohorts is needed to confirm these data, establishing the benefits of a venetoclax-based regimen for this special population.

Keywords: Bcl-2 inhibitor; acute myeloid leukemia; adolescents; targeted therapy; venetoclax; young adults.

Figure 1

Schematic presentation of the distinct patterns of AML frequency and cytogenetic and molecular features between different age groups (image was created using Biorender software version 04, Licence #JC26MALGTX).

Figure 2

Schematic presentation of venetoclax mechanism of action. Venetoclax targets Bcl-2, presenting increased affinity for Bcl-2 and reduced affinity for BclxL, and activates BAX proteins, resulting in mitochondrial outer membrane permeabilization (MOMP), which leads to cell apoptosis (Image was created using Biorender software version 04, Licence #XP26MAAH3Z).