| Abstract: |
Asciminib is the first approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP). The present final analysis of the phase 1, open-label, nonrandomized trial (NCT02081378) assessed the long-term safety, tolerability, and antileukemic activity of asciminib in 115 patients with chronic myeloid leukemia in chronic phase without the BCR::ABL1T315I mutation who received asciminib 10–200 mg twice daily (BID) or 80–200 mg once daily (cutoff: March 14, 2023). Median exposure duration was 5.9 (range, 0–8.4) years; 60.9% of patients continued receiving asciminib through post-trial access. Grade ≥3 adverse events (AEs) occurred in 88 patients (76.5%). AEs led to treatment discontinuation, dose adjustment/interruption, or additional therapy in 15 (13.0%), 74 (64.3%), and 106 (92.2%) patients, respectively. Most first-ever AEs, particularly hematologic AEs, presented within the first year and no new safety signals emerged. Of 56 patients who achieved major molecular response, 50 maintained the response by cutoff; the Kaplan-Meier-estimated probability of maintaining this response for ≥432 weeks (≈ 8.3 years) was 88% (95% confidence interval, 78.2–97.0%). The recommended dose for expansion was determined at 40 mg BID. With up to 8.4 years of treatment, asciminib continued to demonstrate long-term safety and efficacy in this population. © The Author(s) 2025. |
| Keywords: |
adolescent; adult; controlled study; aged; aged, 80 and over; middle aged; young adult; gene mutation; major clinical study; genetics; mutation; clinical trial; constipation; drug tolerability; neutropenia; drug efficacy; drug safety; hypertension; hypophosphatemia; monotherapy; follow up; follow-up studies; imatinib; edema; multiple cycle treatment; anemia; bone marrow suppression; protein kinase inhibitor; leukopenia; thrombocytopenia; vomiting; myalgia; cohort analysis; pathology; abelson kinase; dasatinib; chronic myeloid leukemia; acute lymphoblastic leukemia; arthralgia; drug dose escalation; dyspnea; hyperglycemia; hyperuricemia; pruritus; rash; protein kinase inhibitors; pyrazole derivative; multicenter study; pyrazoles; pleura effusion; headache; bcr abl protein; phase 1 clinical trial; kaplan meier method; drug therapy; nilotinib; leukemia, myelogenous, chronic, bcr-abl positive; hypertriglyceridemia; fusion proteins, bcr-abl; drug exposure; pharmacokinetics; upper respiratory tract infection; fluid retention; antileukemic activity; myeloid leukemia; nicotinamide; leukemia, myeloid, chronic-phase; bosutinib; proto-oncogene proteins c-abl; niacinamide; very elderly; humans; prognosis; human; male; female; article; asciminib; real time reverse transcription polymerase chain reaction
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