Meta-Analysis Highlights Efficacy, Safety Benefits With Asciminib in Chronic Myeloid Leukemia

Asciminib (Scemblix) was associated with superior efficacy and lower rates of adverse effects (AEs) compared with other TKIs for patients with chronic myeloid leukemia (CML) in chronic phase (CP-CML), according to findings from a meta-analysis presented at the 2025 SOHO Annual Meeting.1

To conduct the analysis, investigators assessed outcomes from patients treated in the phase 3 ASCEMBL trial (NCT03106779), the phase 3 ASC4FIRST trial (NCT04971226), and a propensity score–matched (PSM) cohort (n ≈ 796), along with a systemic descriptive review of 9 single-arm studies (n = 568). The median follow-up durations ranged from 24 to 52 weeks.

Findings showed that patients treated with asciminib achieved improved rates of major molecular response (MMR) compared with those administered other TKIs (risk ratio [RR], 1.37; 95% CI, 1.19-1.58; I2 = 0.0%). These improved MMR rates were consistent for patients in ASCEMBL (RR, 1.95; 95% CI, 1.03-3.68; I2 = 5.0%), those in ASC4FIRST (RR, 1.37; 95% CI, 1.16-1.63; I2 = 70.2%), and the PSM cohort (RR, 1.26; 95% CI, 0.95-1.67; I2 = 24.8%).

In the 9 single-arm studies, MMR rates varied from 34% to 79% at assessments ranging from 24 to 96 weeks. Notably, lower MMR rates were observed in patients harboring BCR:ABL1 T315I mutations.

Regarding safety, asciminib was associated with lower rates of grade 3 or higher AEs compared with other TKIs across the meta-analysis population (OR, 0.66; 95% CI, 0.47-0.91; I2 = 0.0%). These findings were consistent in the ASCEMBL population (OR, 0.74; 95% CI, 0.42-1.29; I2 = 33.4%) and the ASC4FIRST population (OR, 0.62; 95% CI, 0.42-0.92; I2 = 66.6%). In the 9 single-arm studies, treatment discontinuation rates ranged from 12% to 43%, and these discontinuations were primarily attributed to intolerance or disease progression.

“Asciminib offers superior efficacy and lower AEs compared with other TKIs in controlled studies, while also showing consistent performance across real-world cohorts,” lead study author Fatih Burak Kaner, MD, of Marion Health in Indiana, and colleagues wrote in a poster presentation of the data. “These results support the growing role of asciminib in CML management, including in [BCR:ABL1] T315I–mutated disease. However, further prospective studies are needed to establish its use as a frontline therapy.”

Asciminib Background

Asciminib is currently approved by the FDA for the treatment of adult patients with newly diagnosed Philadelphia chromosome (Ph)–positive CP-CML; adult patients with previously treated Ph-positive CP-CML; and adult patients with Ph-positive CP-CML with a BCR:ABL1 T315I mutation.2 The newly diagnosed indication was based on data from ASC4FIRST, and findings from ASCEMBL supported the pretreated indication. For previously treated patients harboring a BCR:ABL1 T315I mutation, data from the phase 1 CABL001X2101 study (NCT02081378) supported the approval.

Meta Analysis Rationale and Design

Although asciminib is approved in multiple CML indications, investigators sought to assess the efficacy and safety of the agent vs other TKIs.1 Using the PRISMA guidelines, investigators conducted a comprehensive literature review, pulling data from PubMed, Cochrane, and Embase.

After reviewing 611 articles, investigators conducted the meta-analysis on 3 controlled studies and a systemic descriptive review of 9 single-arm studies. Notably, they included international clinical trials and real-world observational cohorts as part of the review.

The analysis included patients with treatment-naive or previously treated CP-CML, although most patients were pretreated. Patients with or without BCR:ABL1 T315I mutations were included in the review.

Patients were required to be treated with asciminib or a comparator TKI, such as imatinib (Gleevec), bosutinib (Bosulif), ponatinib (Iclusig), or investigator’s choice. Notably, patients treated with a TKI as part of a combination regimen were excluded from the study.

Investigators assessed outcomes in randomized, matched, and observational designs, using R software for statistical analysis.

References

1. Kaner F, Santiago M, Lodi N, Matos U. Efficacy and safety of asciminib compared with other TKIs in CML: meta-analysis of controlled studies and descriptive review of single-arm cohorts. Presented at: 2025 SOHO Annual Meeting; September 3-6, 2025; Houston, TX. Abstract CML-342.
2. Scemblix. Prescribing information. Novartis; 2024. Accessed September 4, 2025. https://www.novartis.com/us-en/sites/novartis_us/files/scemblix.pdf