Treatment Outcomes with Asciminib, the First Allosteric BCR::ABL1 Tyrosine Kinase Inhibitor, in Chronic Myeloid Leukemia Patients with Multiple Resistance to Prior Therapy

AUTOIMMUNE THROMBOCYTOPENIA

AG Turkina, EA Kuzmina

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Elena Andreevna Kuzmina, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(918)167-35-69; e-mail: 1110ekuzmina@gmail.com

For citation: Turkina AG, Kuzmina EA. Treatment Outcomes with Asciminib, the First Allosteric BCR::ABL1 Tyrosine Kinase Inhibitor, in Chronic Myeloid Leukemia Patients with Multiple Resistance to Prior Therapy. Clinical oncohematology. 2023;16(3):311–320. (In Russ).

DOI: 10.21320/2500-2139-2023-16-3-311-320

ABSTRACT

Currently, there is a crucial need for new treatment approaches to overcome the resistance and intolerance of several tyrosine kinase inhibitor (TKI) therapy lines in chronic myeloid leukemia (CML) patients. Asciminib, the first in its class BCR::ABL1-tyrosine kinase inhibitor specifically targeting ABL myristoyl pocket (STAMP), demonstrated efficacy and safety in CML patients with prior TKI therapy failure, including the cases with pan-resistant T315I mutation in the chimeric BCR::ABL1 gene. The present review focuses on the asciminib mechanism of action, the results of both preclinical and clinical phase I and III studies. Due to the favorable cardiovascular toxicity profile of asciminib, the scope of its application can be extended to patients with cardiovascular co-morbidities. Asciminib is registered in the Russian Federation in January 2023, so treatment algorithms for CML patients with ineffectiveness or intolerance of prior therapy should be updated in line with this new option.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, STAMP inhibitors, asciminib, ponatinib, T315I mutation.

Received: April 7, 2023

Accepted: June 15, 2023

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