CML-1296: Asciminib Monotherapy in Chronic Myeloid Leukemia: A Systematic Review of Efficacy and Safety From Phase 1–3 Trials

Document Type

Conference Proceeding

Publication Date

9-1-2025

Publication Title

Clin Lymphoma Myeloma Leuk

Keywords

asciminib, bosutinib, ponatinib, triacylglycerol lipase, adult, adverse drug reaction, cardiovascular disease, chronic myeloid leukemia, clinical practice, clinical trial, conference abstract, controlled study, drug combination, drug comparison, drug therapy, drug withdrawal, female, human, intervention study, major clinical study, male, monotherapy, multicenter study, pharmacology, remission, side effect, systematic review, therapy, thrombocytopenia

Abstract

Although adenosine triphosphate–competitive tyrosine kinase inhibitors (TKIs) have transformed the treatment of chronic myeloid leukemia (CML), long-term outcomes remain limited by resistance, intolerance, and off-target toxicities. Objective: To evaluate the efficacy and safety of asciminib monotherapy across treatment lines, including newly diagnosed, multi-TKI–resistant, and T315I-mutated chronic-phase CML (CML-CP). Design: Systematic review of phase 1–3 interventional trials published or presented through May 2025. Setting: International academic and clinical trial sites. Patients or Other Participants: Adult patients with CML-CP treated with asciminib as monotherapy, including subgroups with prior TKI exposure and T315I mutation. Interventions: Oral asciminib monotherapy across various doses and settings, including 200 mg twice a day in T315I-mutated CML. Main Outcome Measures: Major molecular response (MMR) rates, treatment discontinuation, grade ≥3 adverse events. Results: Ten studies met inclusion criteria. In heavily pretreated CML-CP, the ASCEMBL trial showed superior MMR at 96 weeks with asciminib versus bosutinib (37.6% vs 15.8%), along with lower discontinuation and toxicity rates. In newly diagnosed patients, the ASC4FIRST trial showedMMRof 67.7% vs 49.0% (P < 0.001) at 48 weeks with fewer severe adverse events compared with standard TKIs. For patients with the T315I mutation, asciminib 200 mg twice a day achieved nearly 49%MMRat 2 years, with higher rates in ponatinib-naive patients. A 4-year phase 1 update confirmed durable molecular responses and low vascular toxicity in those with ≥2 prior TKIs. Real-world data supported these findings. Grade ≥3 adverse events were uncommon and primarily included asymptomatic lipase elevation, cardiovascular events, and thrombocytopenia. Conclusions: Asciminib achieves robust molecular responses and exhibits a favorable safety profile across diverse CML-CP populations. Its utility spans frontline use and resistant/mutated settings, supporting its integration into clinical practice. Ongoing trials are evaluating treatment sequencing and treatment-free remission strategies.

Volume

25

First Page

S595

Last Page

S596

Find It @ Sladen

Share

COinS