IMPROVED PATIENT-REPORTED OUTCOMES (PROS) WITH ASCIMINIB (ASC) VS INVESTIGATOR-SELECTED TYROSINE KINASE INHIBITORS (IS-TKIS) IN NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA (CML): ASC4FIRST WK 48 ANALYSIS

Andreas Hochhaus et al.
Universitätsklinikum Jena, Jena, Germany

Background
  • Many patients (pts) with newly diagnosed chronic phase (CP) CML have persistent low-grade adverse events (AEs) that can reduce health-related quality of life (HRQOL) and treatment (tx) adherence and prevent pts from achieving tx goals.
  • CML txs that optimize efficacy, safety, and tolerability are needed. ASC, the first BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket, received FDA approval for newly diagnosed CML-CP based on superior efficacy vs IS-TKIs in the wk 48 analysis of the pivotal ph 3 ASC4FIRST trial (NCT04971226) and is approved worldwide for CML-CP after ≥2 prior TKIs.
  • The authors present PROs from ASC4FIRST (wk 48 analysis cutoff: Nov 28, 2023).
  • The secondary study endpoint for PROs was change from baseline (BL) in EORTC QLQ-C30 and EORTC QLQ-CML24 overall scores and individual scales.
  • Exploratory endpoints for PROs were PRO-CTCAE item scores and the FACT-GP5 item. PRO-CTCAE items were fatigue, vomiting, nausea, loose/watery stools, headache, arm/leg swelling, rash, itchy skin, and aching muscles.
Methods
  • Adults with newly diagnosed CML-CP were randomized 1:1 to receive ASC or an IS-TKI and stratified by ELTS risk category and prerandomization selected TKI (imatinib/second-generation TKI).
  • Pts completed PRO questionnaires on electronic devices (ePRO), and scores were calculated per EORTC scoring manuals. Improvements in QLQ-C30 and QLQ-CML24 items were defined as an increase in score for functional scales and global health status/QOL, and a decrease for symptom scales. 
Results
  • A total of 405 pts were randomized to ASC (n=201) or IS-TKIs (n=204). Median follow-up was 16.3 mo with ASC and 15.7 mo with IS-TKIs. At cutoff, 194 pts with ASC and 195 pts with IS-TKIs had ≥1 PRO assessment. Completion rates in pts on therapy (with PRO assessments at BL and ≥1 post BL) receiving ASC vs IS-TKIs, respectively, were balanced for QLQ-C30 (BL: 57.7% vs 59.0%; wk 48: 80.5% vs 72.3%) and QLQ-CML24 (BL: 56.2% vs 56.4%; wk 48: 79.9% vs 71.0%).
  • Per QLQ-C30, more pts receiving ASC vs IS-TKIs had improvements in fatigue (44.3% vs 38.6%), pain (32.9% vs 20.0%), HRQOL (43.0% vs 27.1%), and cognitive (20.3% vs 12.9%) and social functioning (26.6% vs 17.1%) (Figure). Fewer pts receiving ASC vs IS-TKIs had improvements in financial difficulties (15.2% vs 20.0%) and constipation (10.1% vs 20.0%).  
  • Per QLQ-CML24, more pts receiving ASC vs IS-TKIs had improvements in symptom burden (39.0% vs 16.7%), impact on daily life (61.0% vs 40.9%), worry/mood (49.4% vs 33.3%), and body image (23.4% vs 15.2%), and satisfaction with care and information (44.2% vs 27.3%) (Figure). 
  • Based on PRO-CTCAE, pts receiving ASC vs IS-TKIs had fewer and less severe pain- and gastrointestinal-related AEs, less fatigue, and slightly less severe itchy skin. Per FACT-GP5, 68.4% of pts with ASC and 45.5% with IS-TKIs were not bothered by tx side effects, suggesting better tolerability.
  • Exploratory analyses to evaluate the impact of missing BL PRO data and adjustment of the global health status/QOL domain scoring due to incorrect ePRO programming indicated no substantial impact on conclusions using the PRO data.
Conclusion
  • In ASC4FIRST, ASC was associated with improvements in HRQOL, cognitive and social functioning, symptom burden, and impact on daily life and satisfaction with care and information compared with IS-TKIs at wk 48. PROs, along with the superior efficacy and remarkable safety profile of ASC in ASC4FIRST, continue to support ASC as a tx of choice for newly diagnosed CML-CP.