Favorable tolerability of asciminib versus ATP-competitive tyrosine kinase inhibitors in the ASC4FIRST study of newly diagnosed patients with chronic-phase chronic myeloid leukemia
Year: 2026
Type: article
Abstract: Many patients with chronic myeloid leukemia (CML) treated with adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) experience persistent adverse events (AEs) that negatively impact daily living and the ability to remain on treatment. Asciminib, an allosteric inhibitor of BCR::ABL1, was designed to enhance efficacy and reduce off-target effects vs ATPcompetitive TKIs. The phase 3 randomized ASC4FIRST trial established the overall favorable safety profile of asciminib in patients with newly diagnosed CML in chronic phase (CP). This exploratory post hoc analysis of ASC4FIRST focused specifically on the tolerability of asciminib vs imatinib and asciminib vs second-generation [2G] TKIs. Analyses were conducted within each stratum to account for differences between strata; patients prerandomized to the imatinib stratum were older and had higher cardiovascular risk than those in the 2G stratum. Within both strata, patients receiving asciminib experienced fewer difficult-to-tolerate AEs (such as gastrointestinal toxicity, rash, and pleural effusion) and fewer AEs leading to dose modifications and discontinuations due to nonhematologic and hematologic AEs vs the investigator-selected (IS) TKI comparator, with a shorter median duration of dose modification. Additionally, median onset of AEs leading to dose modification occurred later in patients receiving asciminib vs ISTKIs. The safety and tolerability of asciminib observed in the ASC4FIRST trial demonstrate asciminib's excellent benefit-risk profile as a frontline therapy for a broad range of patients with newly diagnosed CML-CP.
Source: Haematologica
Authors: Ghayas C. Issa, Richard A. Larson, Timothy P. Hughes, Andreas Hochhaus, Naoto Takahashi, Felice Bombaci, Jianxiang Wang, Dong-Wook Kim, Dennis Dong Hwan Kim, Jiri Mayer, Yeow-Tee Goh, Philipp Le Coutre, Inho Kim, Gabriel Etienne, David Andorsky, Ennan Gu, Yifan Zhang, Tracey McCulloch, Nithya Agrawal, Rajendra Jinwal, Andrea Damon, Islam Sadek, Jorge E. Cortes
Institutions: The University of Texas MD Anderson Cancer Center, University of Chicago, South Australian Health and Medical Research Institute, The University of Adelaide, Jena University Hospital, Akita University, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, State Key Laboratory of Experimental Hematology, University Health Network, University of Toronto, Princess Margaret Cancer Centre, Eulji University Uijeongbu Eulji Medical Center, Masaryk University, University Hospital Brno, Singapore General Hospital, Charité - Universitätsmedizin Berlin, Seoul National University, Seoul National University Hospital, Seoul National University Hospital Biomedical Research Institute, Institut Bergonié, Rocky Mountain Cancer Centers, Novartis (Switzerland), Novartis (India), Augusta University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W7167015049
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