B-cell lymphoma-2 inhibition and resistance in acute myeloid leukemia

Abstract

Spurred by better understanding of disease biology, improvements in molecular diagnostics, and the development of targeted therapies, the treatment of acute myeloid leukemia (AML) has undergone significant evolution in recent years. Arguably, the most exciting shift has come from the success of treatment with the B-cell lymphoma-2 inhibitor venetoclax. When given in combination with a hypomethylating agent or low dose cytarabine, venetoclax demonstrates high response rates, some of which are durable. In spite of this, relapses after venetoclax treatment are common, and much interest exists in elucidating the mechanisms of resistance to the drug. Alterations in leukemic stem cell metabolism have been identified as a possible escape route, and clinical trials focusing on targeting metabolism in AML are ongoing. This review article highlights current research regarding venetoclax treatment and resistance in AML with a focus on cellular metabolism.

Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting

“… 3 Finally, although the majority of newly diagnosed patients respond to venetoclax-based combinations, the median duration of response may only be approximately 12 months, which necessitates an understanding of how resistance evolves and how this can be targeted. 23 In our study, we also found that four of 10 CR/CRi patients relapsed, and the median time to relapse was only 5 (1.0–24) months. Therefore, haematopoietic stem cell transplantation (HSCT) is recommended for consolidation therapy in patients with CR after Venetoclax-based treatment; however, most of these patients are ineligible for HSCT due to their old age or poor performance status.…”

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

“…This practice may tend to abandon these drugs, but in less advanced diseases, they may act better. However, the registration of many new drug trials is limited to morphological relapse (>5% fibroblasts) [ 52 ]. The response rate to new therapeutics may be higher if tested in MRD cases, and MRD is the only evidence of disease.…”