Asciminib in the treatment of Philadelphia chromosome-positive chronic myeloid leukemia: Focus on patient selection and outcomes Review


Authors: Hijiya, N.; Mauro, M. J.
Review Title: Asciminib in the treatment of Philadelphia chromosome-positive chronic myeloid leukemia: Focus on patient selection and outcomes
Abstract: Tyrosine kinase inhibitors (TKIs) have significantly changed the treatment of chronic myeloid leukemia (CML) and improved outcomes for patients with CML in chronic phase (CML-CP) and accelerated phase (AP). Now armed with numerous effective therapeutic options, clinicians must consider various patient-and disease-specific factors when selecting the most appropriate TKI across lines of therapy. While most patients with CML expected to have a near-normal life expectancy due to the success of TKIs, emphasis has expanded beyond response and survival to include factors like quality of life, tolerability, and long-term toxicity management. Importantly, a subset of patients can achieve sustained deep molecular response and can attain treatment-free remission. Despite these successes, unmet needs remain related to CML treatment, including the persistent challenge of treatment resistance and intolerance, broadening treatment options for patients with resistance mutations or serious comorbidities, and focus on specific populations such as children and young adults. In particular, the only previously available treatments for patients with CML-CP with the T315I mutation were ponatinib, olverembatinib (exclusively approved for use in China at the time of this writing), omacetaxine, and hematopoietic stem cell transplantation. Asciminib has entered the CML treatment landscape as a new option for adult patients with CML-CP who have received ≥2 prior TKIs or those with the T315I mutation. Asciminib’s unique mechanism of action, Specifically Targeting the ABL Myristoyl Pocket, sets it apart from traditional adenosine triphosphate-competitive TKIs. While asciminib may overcome unmet needs for patients with CML-CP and continues to be studied in other novel settings, guidance on how to integrate asciminib in treatment algorithms is needed. This review focuses on clinical data and how asciminib can overcome current unmet needs, discusses how to individualize patient selection, and highlights future directions to investigate asciminib in earlier lines of therapy and in children and adolescents. © 2023 Hijiya and Mauro.
Keywords: treatment outcome; treatment response; gene mutation; drug tolerability; fatigue; neutropenia; review; diarrhea; drug efficacy; drug potentiation; drug safety; hypertension; patient selection; side effect; drug approval; imatinib; nausea; thrombocytopenia; vomiting; dasatinib; chronic myeloid leukemia; groups by age; tyrosine kinase inhibitors; abdominal pain; rash; alanine aminotransferase; aspartate aminotransferase; comorbidity; headache; nilotinib; drug exposure; pediatrics; phase 3 clinical trial (topic); phase 1 clinical trial (topic); bosutinib; philadelphia chromosome positive cell; ponatinib; human; asciminib; unmet medical need
Journal Title: Cancer Management and Research
Volume: 15
ISSN: 1179-1322
Publisher: Dove Medical Press Ltd  
Date Published: 2023-01-01
Start Page: 873
End Page: 891
Language: English
DOI: 10.2147/cmar.S353374
PROVIDER: scopus
PMCID: PMC10460573
PUBMED: 37641687
DOI/URL:
Notes: Review -- Source: Scopus
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  1. Michael John Mauro
    272 Mauro