How does asciminib compare with TKIs in CML?

Patients with newly diagnosed chronic myeloid leukemia (CML) showed better response rates and higher safety when treated with asciminib compared with standard tyrosine kinase inhibitors (TKIs), according to results from the pivotal ASC4FIRST phase 3 study.

“Asciminib demonstrated significantly superior efficacy and excellent safety and tolerability [versus imatinib and second-generation] TKIs in patients with newly diagnosed CML,” the investigators, led by Andreas Hochhaus, MD, of the Jena University Hospital in Germany, wrote in their abstract presented at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain.

The study evaluated the responses of 405 patients with newly diagnosed CML with no prior treatment except imatinib or second-generation TKIs for ≤2 weeks prior to randomization. Patients were randomized 1:1 to receive asciminib 80 mg once daily or a TKI selected by the investigator at standard label doses.

Additionally, the study included two subgroups for further analysis: patients who had imatinib as their prerandomization selected TKI, and those who were initially prescribed second-generation TKIs.

The asciminib group included 201 patients, while the investigator-selected TKI group included 204 patients. After a median follow-up of 16.3 months, patients in the asciminib group showed superior response rates, with 67.7% achieving a major molecular response (MMR) at week 48 compared with 49.0% in the investigator-selected TKI group.

The subgroup analysis indicated that asciminib had higher efficacy in patients who were initially prescribed imatinib, showing a 69.3% MMR rate at week 48 compared with 40.2% in the investigator-selected TKI group. Asciminib also demonstrated higher efficacy in patients initially prescribed second-generation TKIs, with a 66.0% MMR rate compared with 57.8% in the investigator-selected TKI group.

“By demonstrating better safety and tolerability and faster, deeper responses vsIMA and 2G TKIs, ASC can be the therapy of choice for CML, optimizing the potential to meet [treatment] goals without needing to switch” the researchers wrote in the abstract.

 Reference

Hochhaus A, Hughes T, Cortes J, et al. Asciminib (ASC) provides superior efficacy and excellent safety and tolerability vs tyrosine kinase inhibitors (TKI) in newly diagnosed chronic myeloid leukemia (CML) in the pivotal ASC4FIRST study. Abstract S103. Presented at the European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.