Canadian real-world experience of asciminib treatment in heavily pre-treated chronic myeloid leukemia (CML) patients who failed multiple lines of tyrosine kinase inhibitor (TKI) therapy.

BACKGROUND: Asciminib is a novel drug specifically targeting ABL myristoyl pocket in the ABL1 protein. METHODS: Forty one patients with chronic myeloid leukemia treated with asciminib from 2018 to 2022 were reviewed and analyzed for the efficacy and tolerability of asciminib using real-world experience data. RESULTS: The median age was 60 years (range 17-90) with a past history of a cardiovascular event in 21 patients (51%). Patients were pretreated with a median of 3 previous tyrosine kinase inhibitors (range 1-5). After a median of 12 months of asciminib (range 3-41), major molecular response (MMR) rate was 39% (n = 11/28) and 42% (n = 5/12) at 6 and 12 months, respectively. Molecular response with 2 log reduction (MR2) was noted in 54% (n = 15/28) and 50% (n = 6/12) at 6 and 12 months. The cumulative incidence of MMR and MR2 was 46.3% and 66% at 12 months. Five patients discontinued asciminib due to treatment failure (n = 3) or thrombocytopenia (n = 2). There were no cardiovascular events. Out of 7 patients treated with high dose asciminib for T315I mutation, 5 patients achieved MMR or deeper response. The event-free survival was 63% at 12 months. CONCLUSION: This study confirmed clinical efficacy and tolerability of asciminib with real-world experience.

Clinical outcome of chronic myeloid leukemia patients who switch from first-line therapy with a second generation tyrosine kinase inhibitor to an alternative TKI.

While second generation tyrosine kinase inhibitors (2GTKIs) are highly effective therapies for chronic myeloid leukemia (CML), a significant minority of patients who initiate a 2GTKI will require a switch to an alternative TKI. The long-term outcomes of those who require a change in therapy after front-line 2GTKI therapy are largely undescribed. Here we describe the clinical outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4-90.6 %). Amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2-80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Approximately 25 % of patients who initiate first-line 2GTKI in a real world setting will ultimately switch to an alternate TKI due to intolerance. Patients who switch for intolerance continue to enjoy excellent clinical outcomes.