Asciminib Appears to Benefit All Chronic Myeloid Leukemia Subgroups

According to David Andorsky, MD, asciminib (Scemblix) appears to be better tolerated than second-generation tyrosine kinase inhibitors (TKIs) in those with chronic myeloid leukemia in chronic phase (CML-CP) while yielding benefits across patient subgroups.

CancerNetwork® spoke with Andorsky, medical oncologist, hematologist, and associate chair for the US Oncology Hematology Research and member of the Rocky Mountain Cancer’s Research Executive Committee, about whether there were any patient subgroups who particularly benefitted from treatment with asciminib and how the agent compared with standards of care for patients with CML-CP.

Andorsky explained that interim results from the phase 2 ASC2ESCALATE study (NCT05384587) presented at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH) evaluating asciminib in CML-CP did not answer whether any particular patient subgroup benefitted from the investigational therapy.¹ He then expressed that this question was better answered by the phase 3 ASC4FIRST study (NCT04971226), the results of which were also presented at ASH.²

He further explained that a tolerability benefit was observed with asciminib vs second-generation TKIs across all patient subgroups, noting that there was no single patient subgroup that benefitted more than another. He then explained that the ASC4FIRST trial also highlighted a benefit with asciminib over other standard-of-care TKIs.

According to Andorsky, asciminib attained a statistically significant advantage in molecular response over imatinib and a nonsignificant advantage over second-generation TKIs, which he stated may change with longer follow-up. He then expressed that the safety data for asciminib was favorable, citing fewer instances of grade 3 or 4 adverse events (AEs), as well as fewer treatment-related dose interruptions, reductions, or discontinuations with the investigational agent over investigator’s choice of either imatinib or second-generation TKIs.

Transcript:

[The phase 2 ASC2ESCALATE] study did not directly answer the question [of which subgroups benefitted the most]. It was a fairly small report involving 71 patients, but if you look at [the phase 3 ASC4FIRST trial], which is a much larger study that also presented follow-up data at [ASH 2024], we can see that there was benefit compared with other TKIs across the board [for factors including] gender, age, Sokal score. There is not necessarily one group of patients that is going to benefit more or less. The one thing that is nice about this medication is it is very well tolerated, [likely] better than the other TKIs [based on] the ASC4FIRST data. I think it is applicable to almost anybody.

The ASC4FIRST study looked directly at that question [of how asciminib compared with other TKIs]. These were first-line patients [who] were randomly [assigned] to receive either asciminib or the investigator’s choice of TKI, which was either going to be imatinib [Gleevec] or one of the second-generation TKIs: nilotinib [Tasigna], dasatinib [Sprycel], or bosutinib [Bosulif]. What that study showed during the first presentation we had of the data at the American Society of Clinical Oncology [ASCO] Annual Meeting this past year and now at ASH this year, is that the major molecular response rates were higher for asciminib vs imatinib in a statistically significant fashion, and also against second-generation TKIs, which did not quite reach statistical significance yet, but the gap between those 2 [treatments] is widening with longer follow-up.

[Asciminib] does appear to compare favorably to the other [TKIs] in terms of efficacy. In terms of safety, it also compares favorably. There were fewer grade 3 or 4 adverse events compared to investigator’s choice [of TKI], and also fewer treatment discontinuations, interruptions, or dose reductions of asciminib vs the other TKIs. Both appear to be, based on that data, better tolerated and potentially more efficacious.

References

1. Atallah EL, Levy MY, Koller PB, et al. Efficacy and safety of asciminib in chronic myeloid leukemia in chronic phase (CML-CP): interim results from the phase 2 asc2escalate trial in the cohort of patients (Pts) after 1 prior tyrosine kinase inhibitor (TKI). Blood. 2024;144 (suppl 1):479. doi:10.1182/blood-2024-200717
2. Cortes JE, Hochhaus A, Hughes TP, et al. Asciminib (ASC) demonstrates favorable safety and tolerability compared with each investigator-selected tyrosine kinase inhibitor (IS TKI) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) in the pivotal phase 3 ASC4FIRST study. Blood. 2024;144(suppl 1):475. doi:10.1182/blood-2024-203757