ASC4REAL: Efficacy and tolerability comparison between ASCEMBL study, a phase 3 randomized clinical trial (RCT), and consolidated real-world (RW) experience with asciminib (ASC) in patients with CML beyond two TKIs.

Abstract

e18519 Background: Despite advances in the management of chronic myeloid leukemia (CML), effective treatment options in later lines are limited. Treatment failure rates increase with each line of treatment and sequential tyrosine kinase inhibitor (TKI) therapy is associated with increased resistance. Importantly, almost all TKIs in the clinics target the ATP-binding site potentially resulting in off-target effects and long-term tolerability issues. Although data for ASC, a novel allosteric TKI targeting the myristoyl pocket, is emerging in the RW setting, low patient numbers in ASC RW studies hinders a robust comparison with the larger phase 3 RCT study. Methods: Post systematic literature search, data from 9 published or publicly presented RW studies was extracted. 319 CML patients that received ASC beyond 2 TKIs were included in this analysis. RW studies that had less than 10 patients were excluded. The results were then compared to estimates from the ASCEMBL study. Results: Compared to the RCT, RW studies showed similar or higher efficacy based on major molecular response (MMR) and deep molecular response (DMR) rates, achieved in shorter time. Rate of discontinuation of ASC was also lower in the RW setting. Similarly, some adverse events, specifically thrombocytopenia and arterial occlusive events (AOE) were lower, while some such as myalgia were higher in the RW setting when compared with the RCT. Conclusions: This analysis demonstrates ASC as an effective TKI for CML patients in the RW setting, supporting the results from the ASCEMBL RCT. [Table: see text]