Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after ≥1 prior tyrosine kinase inhibitor: 2-year follow-up results

Jorge E. Cortes, Koji Sasaki, Dong Wook Kim, Timothy P. Hughes, Gabriel Etienne, Michael J. Mauro, Andreas Hochhaus, Fabian Lang, Michael C. Heinrich, Massimo Breccia, Michael Deininger, Yeow Tee Goh, Jeroen J.W.M. Janssen, Moshe Talpaz, Valle Gomez Garcia de Soria, Philipp le Coutre, Daniel J. DeAngelo, Andrea Damon, Silvia Cacciatore, Fotis PolydorosNithya Agrawal, Delphine Rea

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1 Citation (Scopus)


Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1T315I, 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::ABL1IS ≤1%. Of 45 evaluable patients, 48.9% achieved a major molecular response (MMR, BCR::ABL1IS ≤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. (Figure presented.)

Original languageEnglish
Publication statusAccepted/In press - 2024

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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