Asciminib is a novel tyrosine kinase inhibitor that specifically targets the myristoyl pocket. It has increased selectivity and potent activity against BCR-ABL1 and the mutants that most frequently prevent the activity of the ATP-binding competitive inhibitors. Results for clinical trials in patients with chronic myeloid leukemia that have received 2 or more tyrosine kinase inhibitors (randomized against bosutinib) or who have a T315I mutation (single arm study) have shown high levels of activity and a favorable toxicity profile. Its approval has offered new options for patients with these disease features. There are however a number of unanswered questions that remain to be defined including the optimal dose, understanding the mechanisms of resistance and, importantly, how it compares to ponatinib in these patient populations where we now have these two options available. Ultimately, a randomized trial is needed to answer questions to which we currently offer speculative informed guesses. The novelty of its mechanism of action and the exciting early data offers the potential for asciminib to address some of the remaining needs in the management of patients with chronic myeloid leukemia, including second line therapy after resistance to a frontline second generation tyrosine kinase inhibitors and improving in the success of treatment free remission. Multiple studies are ongoing in these areas and one can only hope that the desired randomized trial comparing to ponatinib will occur soon.
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