medwireNews: Asciminib has superior efficacy and better tolerability than standard frontline tyrosine kinase inhibitors (TKIs) in people with a new diagnosis of chronic myeloid leukemia (CML), according to ASC4FIRST data presented at the EHA2024 Hybrid Congress.
Study investigator Andreas Hochhaus (Universitätsklinikum Jena, Germany) told the audience in Madrid, Spain, that “asciminib may extend and improve the options for first-line treatment of CML in chronic phase.”
He explained that asciminib is a BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket that “was intentionally designed to be highly specific and minimize off-target effects,” and it is already approved in the third-line setting.
The current phase 3 trial evaluated asciminib in the first line, randomly assigning 405 patients who had not received prior TKIs for Philadelphia chromosome-positive, chronic-phase CML to receive either asciminib 80 mg/day (n=201) or any of the currently available TKIs (n=204). The TKI to be used was selected by the physician in consultation with the patient before randomization and participants were stratified by TKI into two groups – 102 patients receiving imatinib and 102 other second-generation TKIs.
The co-primary endpoint of major molecular response (MMR) at 48 weeks was achieved by a significantly greater proportion of patients in the asciminib than all TKIs group, at rates of 67.7% versus 49.0%.
The other primary endpoint of the study was also met, with a significantly higher MMR rate at week 48 among the 101 patients in the asciminib group who were compared with the 102 patients receiving imatinib as their TKI, at 69.3% and 40.2%, respectively.
Hochhaus pointed out that asciminib was associated with “early and deep molecular responses” relative to control in the overall study population and within the imatinib stratum.
The agent also “demonstrated favorable safety and tolerability” versus imatinib and second-generation TKIs, he continued, with rates of grade 3 or worse adverse events (AEs) of 38.0% versus 44.4% and 54.9%, respectively.
A lower proportion of patients given asciminib than imatinib or second-generation TKIs needed dose interruptions and adjustments due to AEs, at 30.0% versus 39.4% and 52.9%, respectively, and this was also the case for discontinuations as a result of AEs, at 4.5% versus 11.1% and 9.8%.
Arterial-occlusive events are an AE of special interest with asciminib, and there were two any-grade events and one event of grade 3 or worse each in the asciminib and second-generation TKI groups, and none in the imatinib group.
“As incidence of [arterial-occlusive events] is known to increase with longer exposure, longer follow-up is needed to better assess the long-term risk,” said the presenter.
These results were published simultaneously in The New England Journal of Medicine and presented previously at the 2024 ASCO Annual Meeting in Chicago, Illinois, USA.
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EHA2024 Hybrid Congress; Madrid, Spain: 13–16 June
N Engl J Med 2024; doi:10.1056/NEJMoa2400858
2024 ASCO Annual Meeting; Chicago, Illinois, USA: 31 May–4 June
