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

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

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