Excellent phase 3 results for asciminib in chronic myeloid leukaemia

Asciminib was superior to all other tested first-line tyrosine kinase inhibitors (TKIs) in participants with chronic myeloid leukaemia (CML). Also, asciminib treatment was associated with fewer adverse events than the standard-of-care TKIs in the ASC4FIRST trial.

“Many newly diagnosed patients with CML do not achieve an optimal response with standard TKIs,” opened Prof. Andreas Hochhaus (Jena University Hospital, Germany) [1]. “Moreover, long-term use of TKIs has been linked to renal failure, pleural effusion, and other adverse events.” The phase 3 ASC4FIRST trial (NCT04971226) randomised 405 participants with untreated CML in the chronic phase 1:1 to the new-generation BCR::ABL1 TKI inhibitor asciminib or an investigator-selected standard-of-care TKI.

Treatment with the first-generation TKI imatinib, or one of the second-generation TKIs bosutinib, dasatinib, or nilotinib was permitted for ≤ 2 weeks before randomisation. Prof. Hochhaus presented the results and noted that randomisation was stratified by pre-randomisation TKI selection and the European Long-Term Survival (ELTS) risk category. The primary endpoints were major molecular response (MMR) at week 48 and MMR within the imatinib stratum.

The first primary endpoint was met:  67.7% of the participants in the asciminib and 49.0% in the control arm reached an MMR at week 48 (Δ 18.9; 95% CI 9.6–28.8; P<0.001). In addition, MR^4.5 (BCR::ABL1 ≤0.0032%) was seen in 16.9% of participants in the asciminib arm compared with 8.8% in the control arm (see Figure). In the imatinib stratum, the MMR rates were 69.3% and 40.2%, in favour of the asciminib arm, meeting the second primary endpoint (Δ 29.6; 95% CI 16.9–42.2; P<0.001). Of note, the difference in MMR between the asciminib arm (66.0%) and control arm (57.8%) within the second-generation TKI stratum was less pronounced (95% CI -5.1 to 21.5).

Figure: More participants achieved early/deep molecular responses with asciminib as compared with investigator-selected TKIs [1]



EMR, early molecular response; IS, investigator-selected; MR, molecular response; TKIs, tyrosine kinase inhibitors.

Fewer grade ≥3 adverse events were documented in the asciminib arm (38.0%) compared with participants who received imatinib (44.4%) or second-generation TKIs (54.9%). Similarly, the adverse events-related treatment discontinuation rate was lower (4.5% vs 11.1% and 9.8%) on asciminib. “We saw less neutropenia, anaemia, and lymphopenia with asciminib,” added Prof. Hochhaus. Also, diarrhoea, nausea, and muscle spasms were less common in the asciminib arm.

Asciminib displayed a favourable safety profile and provided better efficacy outcomes than first-line standard-of-care TKIs in newly diagnosed participants with CML in the chronic phase.

1. Hochhaus A, et al. Asciminib provides superior efficacy and excellent safety and tolerability vs tyrosine kinase inhibitors in newly diagnosed chronic myeloid leukemia in the pivotal ASC4FIRST study. S103, EHA congress 2024, 13–16 June, Madrid, Spain.

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Posted on 12 August 202412 August 2024