At the 2024 annual meeting of the American Society of Clinical Oncology (ASCO), Timothy Hughes, MD presented data from the phase 3 ASC4FIRST clinical study demonstrating that treatment with the STAMP inhibitor asciminib in newly diagnosed patients with chronic phase chronic myeloid leukemia (CML) resulted in superior response rates and better tolerability over standard-of-care tyrosine kinase inhibitors (TKIs).
The international study randomly assigned 405 patients with recently diagnosed chronic phase CML to treatment with asciminib (n=201) or an investigator selected TKI (n=204; 102 received imatinib and 102 received a second generation TKI). The co-primary endpoints of the study were 48-week major molecular response (MMR) for asciminib vs all investigator-selected TKIs and 48-week MMR for asciminib vs the imatinib stratum. Asciminib vs the second-generation TKI stratum was a secondary endpoint.
The median patient age was 52 years. While the study was well-balanced for baseline characteristics between the arms, patients on the imatinib stratum of the investigator-selected TKI arm tended to be older and have higher-risk disease.
At week 48, 68% of patients in the asciminib arm had achieved a major molecular response (MMR) compared with 49% of patients receiving a TKI. Rates of 12-week molecular response (90% vs 70%), 48-week MR4 (39% vs 21%), and 48-week MR4.5 (17% vs 9%) were also higher with asciminib vs investigator-assessed TKI, respectively.
Subset analysis demonstrated similar results in patients treated with asciminib vs imatinib (48-week MMR: 69% vs 40%, MR 4.5: 88% vs 60%, MR4.5: 18% vs 5%; 12-week early molecular response, 88% vs 60%). There was no significant difference in these parameters when asciminib was compared to patients treated with second generation TKIs, although these numbers were numerically higher with asciminib.
With a median follow-up of 16.3 months with asciminib and 15.7 months with investigator-selected TKIs, more patients remained on treatment with asciminib with 13.4% discontinuing on the asciminib arm vs 29.9% on the TKI arm. These differences were largely due to lower rates of treatment failure and adverse events leading to treatment discontinuation with asciminib. In addition, there were fewer grade 3 or higher adverse events and adverse events leading dose modification or interruption with asciminib vs imatinib or second-generation TKIs. The most frequent adverse events in the asciminib arm were low platelet count (13%) and low neutrophil count (10%).
These data suggest asciminib is a potential new frontline option for chronic phase CML. However longer-term data on tolerability, financial considerations, and deep molecular responses are needed to guide treatment selection. The study was published simultaneously in the New England Journal of Medicine.
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