An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors

ABSTRACT

Introduction

To date, five tyrosine kinase inhibitors (TKIs) are available for treating chronic myeloid leukemia (CML) patients in clinical practice. Despite this, a significant proportion of patients will ultimately develop failure to approved TKIs due to intolerance or resistance. Consequently, new treatment approaches are still required in this unmet clinical need. Asciminib, a first-in-class BCR::ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to prior TKI treatment.

Areas covered

This review will cover the mechanism of action, pharmacokinetic profile, and clinical data of asciminib based on available information from laboratory studies, clinical trials, and real-world evidence.

Expert opinion

Recent approval of asciminib will require positioning of this drug in the treatment algorithm of CML patients failing initial TKI therapy. Available data support the lack of cross-intolerance of asciminib with other TKIs and its favorable cardiovascular toxicity profile. In addition, asciminib has demonstrated considerable efficacy in CML patients who have failed at least two TKIs, although preliminary data suggest that this efficacy may be lower in those previously exposed to ponatinib. The introduction of asciminib in clinical practice may represent an important step forward in the management of CML.

KEYWORDS:

• Allosteric inhibition
• asciminib
• chronic myeloid leukemia
• intolerance
• resistance
• STAMP inhibitor
• tyrosine kinase inhibitors

Article highlights

• The management of CML patients failing 2GTKIs is a challenging clinical situation.

• Asciminib is a first-in-class BCR::ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket.

• Available data support that asciminib is a well-tolerated and effective treatment for CML patients failing at least two TKIs.

• Asciminib has obtained FDA approval for CML-CP patients failing at least two TKIs and, presumably, will become available worldwide soon.

Declaration of Interest

V García-Gutiérrez declares advisory board and speaker bureau honoraria from Novartis, BMS, and Pfizer.

JC Hernández-Boluda declares advisory board and speaker bureau honoraria from Novartis and Incyte.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript has received advisory board and speaker bureau honoraria from Novartis. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose. Novartis provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.