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Clinical Trial
. 2025 Aug 26;9(16):4248-4259.
doi: 10.1182/bloodadvances.2025016042.

Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL

Affiliations
Clinical Trial

Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL

Michael J Mauro et al. Blood Adv. .

Abstract

The efficacy of and disease control afforded by tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia in chronic phase (CML-CP) have led to increased longevity and thus the continued pursuit of alternative therapies that are efficacious and maximize tolerability. The 24- and 96-week analyses from ASCEMBL demonstrated superior efficacy, safety, and tolerability of asciminib when compared with bosutinib in later-line therapy, thereby meeting the primary and key secondary objectives. With nearly 4 years of follow-up, data from ASCEMBL continued to demonstrate the superior efficacy, safety, and tolerability of asciminib over bosutinib. At week 156, the major molecular response (MMR) rates remained higher with asciminib (33.8%) than with bosutinib (10.5%); the difference in MMR rates between arms, after adjusting for baseline major cytogenetic response, was 23.2% (95% confidence interval, 13.14-33.18; 2-sided P < .001). Asciminib continued to cause fewer grade ≥3 adverse events (AEs; 59.6% vs 68.4%) and fewer AEs that led to treatment discontinuation (8.3% vs 27.6%) than bosutinib. This updated analysis also includes patients who switched to asciminib because of a lack of efficacy with bosutinib. Two of the 25 patients who switched achieved MMR by the end of study, suggesting that earlier incorporation of asciminib, before other TKIs, may improve responses, albeit modestly. These long-term results further solidify asciminib as the therapy of choice for patients with CML-CP who were previously treated with ≥2 previous TKIs. This trial was registered at clinicaltrials.gov as #NCT03106779.

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Conflict of interest statement

Conflict-of-interest disclosure: A.H. received institutional research support from Novartis, Bristol Myers Squibb, Incyte, and Pfizer; and personal fees from Novartis and Incyte. D.R. received personal fees from Novartis, Pfizer, and Incyte. C.B. received grants from Novartis during the conduct of the study. Y.M. received honoraria from Bristol Myers Squibb, Novartis, Pfizer, and Astellas. J.E.C. received grants and consulting fees from Novartis and Pfizer; and grants from Bristol Myers Squibb. T.P.H. received grants and honoraria for serving on advisory boards and for symposia from Novartis and grants from Bristol Myers Squibb. J.F.A. received honoraria from Incyte and Paladin; received research funding from Incyte; received honoraria for lecturing from Novartis, Pfizer, and R-Pharm; and is an National Institute for Health and Care Research (NIHR) emeritus senior investigator and acknowledges the support of the Imperial NIHR Biomedical Research Centre. E.L. received grants from Novartis; and personal fees and nonfinancial support from Novartis, Pfizer, and Bristol Myers Squibb. S.V. received personal fees from Novartis, AbbVie, Janssen, Sanofi, BIOCAD, Takeda, and AstraZeneca; and nonfinancial support from Pfizer, Novartis, AbbVie, Janssen, Sanofi, and BIOCAD. D.-W.K. received grants from Novartis, Bristol Myers Squibb, Pfizer, ILYANG, and Takeda. A.A. received honoraria from Novartis and Takeda. P.l.C. received speaker’s honoraria from Novartis, Incyte, Pfizer, and Bristol Myers Squibb. K.S. received research funding and honoraria for serving on advisory boards from Novartis. D.D.H.K. received grants, honoraria, and consulting fees from Novartis; grants from Bristol Myers Squibb; and honoraria from Pfizer and Paladin. S.S. received honoraria, grants, and personal fees from Novartis; and grants and personal fees from Bristol Myers Squibb and Incyte. L.C. received honoraria for advisory boards from Otsuka and Novartis; consultancy fees from Keros Therapeutics; and honoraria from Otsuka, Novartis, and Keros Therapeutics. V.G.-G. received grants, nonfinancial support, and honoraria from Novartis, Pfizer, Bristol Myers Squibb, and Incyte. S.K., N.E., and V.D. report being employees of Novartis. M.J.M. reports receiving personal fees from Bristol Myers Squibb, Takeda, and Pfizer. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
MMR and BCR::ABL1IS ≤1% at week 156. MMR (BCR::ABL1IS ≤0.1%). ∗Based on the full analysis set. In patients without MMR at week 156, the reasons were treatment failure (asciminib, n = 3; bosutinib, n = 5), missing assessments (asciminib, n = 3), and lost response (asciminib, n = 1). †The treatment difference, after adjusting for the baseline MCyR status, was 23.16% (95% CI, 13.14-33.18; 2-sided P < .001) at week 156. ‡Based on 142 of 157 patients (90.4%) who received asciminib and 72 of 76 (94.7%) who received bosutinib with BCR::ABL1IS >1% at baseline. §The treatment difference after adjusting for MCyR status at baseline was 32.34% (95% CI, 21.44-43.24; 2-sided P < .001) at week 156.
Figure 2.
Figure 2.
MMR rate difference (95% CI) between treatment at week 156 from subgroup analyses. ∗Patients with T315I and V299L BCR::ABL1 mutations or a nonevaluable mutation assessment were excluded from the subgroup analysis. CRF, case report form.
Figure 3.
Figure 3.
Cumulative incidences of molecular responses. Cumulative incidence of MMR (A) and BCR::ABL1IS ≤1% (B). ∗Nonresponders were censored at their last molecular assessment date. †Discontinuation from treatment for any reason without previous achievement of MMR was considered a competing event. ‡Based on 142 of 157 patients (90.4%) who received asciminib and 72 of 76 (94.7%) who received bosutinib with BCR::ABL1IS >1% at baseline. §Discontinuation from treatment for any reason without previous achievement of BCR::ABL1IS ≤1% was considered a competing event. ||The probability of BCR::ABL1IS ≤1% was not estimable from week 104 onward because no patients were eligible to achieve BCR::ABL1IS ≤1%. NE, not estimable.
Figure 4.
Figure 4.
All-grade AEs by time period with asciminib. ∗Includes thrombocytopenia and platelet count decreased. †Includes neutropenia and neutrophil count decreased. ‡Includes anemia, hemoglobin decreased, and macrocytic anemia. §A patient with multiple occurrences of an AE is counted only once in that time period. Percentages were rounded to the nearest whole number. The denominator for incidence is the number of patients who were ongoing at the beginning of each time period who have not yet experienced the event. The denominator for prevalence is the number of patients who were ongoing at the beginning of each time period. ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Comment in

  • Asciminib in late-line CML treatment.
    Sweet K, Pinilla-Ibarz J. Sweet K, et al. Blood Adv. 2025 Aug 26;9(16):4317-4318. doi: 10.1182/bloodadvances.2025016874. Blood Adv. 2025. PMID: 40827887 Free PMC article. No abstract available.

References

    1. Bower H, Björkholm M, Dickman PW, Höglund M, Lambert PC, Andersson TM. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol. 2016;34(24):2851–2857. - PubMed
    1. Santos FP, Kantarjian H, Quintás-Cardama A, Cortes J. Evolution of therapies for chronic myelogenous leukemia. Cancer J. 2011;17(6):465–476. - PMC - PubMed
    1. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966–984. - PMC - PubMed
    1. Flynn KE, Atallah E. Quality of life and long-term therapy in patients with chronic myeloid leukemia. Curr Hematol Malig Rep. 2016;11(2):80–85. - PMC - PubMed
    1. Druker BJ, Guilhot F, O'Brien SG, et al. IRIS Investigators Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–2417. - PubMed

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