Efficacy and Safety of Asciminib Dose Escalation in Patients with Chronic Myeloid Leukemia (CML) without Optimal Response to the Standard Dose

Introduction: Asciminib (ASC) is a highly effective STAMP inhibitor for the treatment of patients (pts) in the chronic phase (CP) of chronic myeloid leukemia (CML). However, approximately half of pts previously treated with ≥2 tyrosine kinase inhibitors (TKIs) do not achieve an optimal response to the standard dose (SD = 80 mg/day) of the drug.

Study objective: To evaluate the long-term efficacy and safety of increasing the dose of ASC in patients with CP CML without BCR::ABL^T315I mutation and no optimal response to SD.

Materials and methods: ASC dose was escalated up to 120-400mg in 10 patients (6 men) after at least  12 months SD therapy due to absence of any molecular response (MR = BCR::ABL >10%) in 4 Pts or a major molecular response (MMR) in 6 pts (5/6 pts were in MR2, but never reached MMR). At the time of ASC escalation: the median age of Pts was 54.4 (28-72) years, the median number of previous TKIs was 3 (2-6) and the median duration of SD of ASC therapy was 18.7 (14-49.2) months. 

Results: At the time of date collection the median duration of high dose (HD) ASC therapy was 30.8 (7.9-37.7) months. Six (60%) pts ongoing HD of ASC during 45.4 (17-73.1) months and 4 other pts were switched to other TKIs due to lack of optimal response after 13.7 (7.9-33.9) months of HD ASC. Among pts with MR0 only 1/4 (25%) reach MMR after re-escalating ASC dose from 160mg to 400mg. Among Pts with lower initial level of BCR::ABL 4/6 (66.7%) reach stable MMR after 3, 6, 9 and 24 months of HD therapy. No new grade 3-4 AEs were recorded after the ASC dose escalation. Duration of follow up for the start of HD ASC was 38.9 months (26-43.9) months. All patients are alive without progression to the advanced phases of the disease.

Conclusion: The ASC dose escalation was effective – half of our pts reach at least MMR.  High dose of ASC was safe; It seems that ASC dose escalation should be suggested in CP CML pts without MMR on SD