Abstract Introduction Long-term TKI therapy for patients (pts) with CML is efficacious but is associated with adverse events (AEs) affecting quality of life (QOL). Even low-grade AEs can inhibit QOL, resulting in treatment nonadherence and subsequently poor clinical outcomes. Thus, effective management of CML requires assessing the impact of treatment-emergent AEs on QOL. ASC, the first BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket, is approved in several countries for pts with newly diagnosed CML in chronic phase (CP) based on superior clinical outcomes vs IS-TKIs in the pivotal phase 3 ASC4FIRST trial (NCT04971226). In the wk 48 ASC4FIRST PRO analysis, ASC vs IS-TKIs was associated with improved health-related QOL (HRQOL) and reduced symptom burden. Here, we present PROs from the wk 96 analysis (data cutoff: Oct 22, 2024). Methods Adults with newly diagnosed CML-CP were randomized 1:1 to receive ASC or an IS-TKI, stratified by ELTS risk category and prerandomization-selected TKI (imatinib IMA/second-generation 2G TKI). Wk 96 PRO secondary endpoints were change from baseline (BL) in scores and individual scales for EORTC QLQ-C30 and EORTC QLQ-CML24; improvement corresponded to a change from BL in functional/satisfaction and global health status/QOL scales (increase of 5) or symptom/item scores (decrease of 5). PRO-CTCAE items and FACIT-GP5 will be reported separately by Hughes et al. Pts completed questionnaires on electronic devices at BL and scheduled study visits. Results A total of 405 pts were randomized to ASC (ASCIMA, n=101; ASC2G, n=100) or IS-TKIs (IS-TKIIMA, n=102; IS-TKI2G, n=102); median duration of follow-up was 26.9 and 26.3 months per arm, respectively. Completion rates were balanced with ASC vs IS-TKI for EORTC QLQ-C30 (BL, 57.7% vs 59.0%; wk 96, 76.2% vs 65.2%) and EORTC QLQ-CML24 (BL, 56.2% vs 56.4%; wk 96, 75.5% vs 65.2%). Per EORTC QLQ-C30 at wk 96 vs BL, the following proportions of pts on ASCIMA and IS-TKIIMAand on ASC2G and IS-TKI2G had improvement in the physical (31.3% and 17.6%; 43.5% and 40.0%), role (18.8% and 5.9%; 20.6% and 8.6%), cognitive (18.7% and 5.9%; 18.0% and 8.6%), social (25.0% and 17.7%; 33.3% and 22.9%), and emotional (40.7% and 23.5%; 35.9% and 34.2%) functional scales, respectively.The proportions of pts reporting improvement with ASCIMA and IS-TKIIMAand with ASC2G and IS-TKI2G across symptoms included: fatigue (43.8% and 11.8%; 43.6% and 28.5%), nausea/vomiting (15.6% and 0.0%; 7.7% and 2.9%), diarrhea (18.8% and 17.6%; 10.3% and 11.4%), pain (15.7% and 5.9%; 33.4% and 14.3%), dyspnea (9.4% and 0.0%; 12.8% and 5.7%), insomnia (18.8% and 5.9%; 12.8% and 20.0%), appetite loss (25.0% and 5.9%; 25.6% and 11.4%), and constipation (18.8% and 11.8%; 7.7% and 20.0%), respectively. The proportion of pts on ASCIMA and IS-TKIIMAand on ASC2G and IS-TKI2Gwho had improvement with financial difficulties was (18.8% and 29.4%; 23.1% and 20.0%). Overall, 37.5% vs 17.7% of pts receiving ASCIMA vs IS-TKIIMA and 58.9% vs 28.6% receiving ASC2G vs IS-TKI2G, respectively, had improvements in global health status/QOL. Change from BL to wk 96 in EORTC QLQ-CML24 satisfaction/symptom scale scores with ASCIMA vs IS-TKIIMAand with ASC2G vs IS-TKI2G, respectively, showed that higher proportions of pts had improvements in symptom burden (27.5% vs 0.0%; 46.1% vs 20.6%), impact on daily life (62.0% vs 23.5%; 58.9% vs 47.1%), impact on worry/mood (48.2% vs 29.5%; 58.9% vs 41.2%), body image problems (27.6% vs 0.0%; 28.2% vs 11.8%), and satisfaction with care and information (41.4% vs 29.4%; 53.8% vs 29.4%). Improvement in satisfaction with social life was reported by 24.1% and 23.5% of pts on ASCIMA and IS-TKIIMA,and 41.0% and 20.6% on ASC2G and IS-TKI2G, respectively. Exploratory sensitivity analyses evaluating the impact of missing BL PRO data concluded that there was no substantial impact on observed PROs. Conclusions Overall,ASC continued to be associated with improved HRQOL and reduced symptom burden vs IS-TKIs, regardless of strata, in the wk 96 PRO analysis of ASC4FIRST. Considering the superior efficacy and favorable safety and tolerability of ASC in ASC4FIRST observed at wk 96, these PRO findings reinforce ASC as a standard of care for pts with newly diagnosed CML-CP. Longer follow-up of PRO evaluations is warranted and may support long-term QOL benefit of ASC in pts with CML-CP.
Flynn et al. (Mon,) studied this question.