PMID- 36949155 OWN - NLM STAT- MEDLINE DCOM- 20230511 LR - 20240417 IS - 1476-5551 (Electronic) IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 37 IP - 5 DP - 2023 May TI - Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results. PG - 1048-1059 LID - 10.1038/s41375-023-01860-w [doi] AB - Asciminib is approved for patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) who received >/=2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10-200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After approximately 4-year median exposure, 69.6% of patients remained on asciminib. The most common grade >/=3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1