Jorge E Cortes, Nithya Agrawal, Fotis Polydoros, Silvia Cacciatore, Andrea Damon, Valle Gomez Garcia de Soria, Yeow Tee Goh, Michael Deininger, Timothy P Hughes, Massimo Breccia, Andreas Hochhaus, Delphine Rea, Koji Sasaki, Philipp le Coutre, Dong-Wook Kim, Michael J Mauro, Moshe Talpaz, Michael C Heinrich, Fabian Lang, Daniel J DeAngelo, Gabriel Etienne, Jeroen J W M Janssen
Journal: Leukemia 2024;38(7):1522-1533
PMID: 38755421
Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1, which is resistant to most approved adenosine triphosphate-competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic activity of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years' median exposure, 56.3% of patients continued receiving asciminib. Overall, 62.2% of evaluable patients achieved BCR::ABL1 ≤1% on the International Scale (IS); 47.6% and 81.3% of ponatinib-pretreated and -naive patients, respectively, achieved BCR::ABL1 ≤1%. Of 45 evaluable patients, 48.9% achieved a major molecular response (MMR, BCR::ABL1 ≤0.1%), including 34.6% and 68.4% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade ≥3 adverse events (AEs) included increased lipase level (18.8%) and thrombocytopenia (14.6%). Five (10.4%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib's effectiveness, including in almost 50% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.
© 2024. The Author(s).
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