Venetoclax: A Game Changer in the Treatment of Younger AML Patients?

Author:

Molica Matteo1ORCID,Perrone Salvatore2ORCID,Federico Vincenzo3,Alati Caterina4,Molica Stefano5ORCID,Rossi Marco16

Affiliation:

1. Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy

2. Department of Hematology, Polo Universitario Pontino, S.M. Goretti Hospital, 04100 Latina, Italy

3. Hematology and Transplant Unit, Vito Fazzi Hospital, 73100 Lecce, Italy

4. Hematology Unit, Department of Hemato-Oncology and Radiotherapy Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, 89124 Reggio Calabria, Italy

5. Queens Centre for Oncology and Haematology, Castle Hill Hospital, Hull University NHS Trust, Hull HU16 5JQ, UK

6. Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy

Abstract

The combination approach based on venetoclax (VEN) with azacytidine (AZA) has significantly improved outcomes for elderly patients with acute myeloid leukemia (AML). This innovative approach has led to higher rates of overall response, measurable residual disease (MRD)-negative remissions, and overall survival compared with AZA monotherapy. As a result, this combination has emerged as the gold-standard treatment for elderly or unfit patients with AML who are not eligible for intensive therapy. In younger, fit patients with AML, intensive induction and consolidation chemotherapy is commonly used as a first-line approach; however, relapse continues to be the main reason for treatment failure in approximately 30–40% of patients. Efforts to improve MRD-negative response rates and to facilitate the transition to allogeneic hematopoietic stem cell transplantation, particularly in high-risk AML, have inspired trials exploring the combination of intensive chemotherapy with targeted agents. VEN, a first-in-class anti-BCL2 agent, combined with intensive chemotherapy regimens has shown deep MRD-negative remissions, producing prolonged event-free survival and enhancing the transition to allogeneic transplant in first-complete-remission patients. These benefits support the incremental advantages of adding VEN to intensive chemotherapy approaches across ELN risk subcategories, and provides a robust benchmark to design future trials. In this review, we will discuss current studies assessing the efficacy of frontline regimens integrating VEN into intensive chemotherapy in younger patients with AML and specific molecularly defined subgroups.

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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