Among patients with chronic myeloid leukemia in chronic phase (CML-CP) who relapse after or who are refractory to at least 2 prior tyrosine kinase inhibitors (TKIs), asciminib appears to be superior to bosutinib, according to research published in Blood.

TKIs targeting the BCR-ABL1 oncoprotein have drastically improved survival of patients with CML over the past several decades, with many patients reaching a normal or near-normal life expectancy. While many patients respond to these therapies, some CML cases do not respond, and show either initial or secondary resistance to TKI treatment.

In the third line, therapy in this population becomes more complex, and many patients experience serious adverse events. Bosutinib, for example, is a second-generation TKI approved for use in some patients with CML who do not respond or who stop responding to first-line therapies, although its use is not yet optimally defined.


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Asciminib, a novel Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor, prevents the kinase activity of BCR-ABL1, and has shown promise in prior study of CML. For this randomized phase 3 study (ClinicalTrials.gov Identifier: NCT03106779), researchers compared the safety and efficacy of asciminib with that of bosutinib among patients with CML-CP who had received at least 2 prior TKI lines.

Overall, 233 patients were included. Patients were randomly assigned to receive asciminib 40 mg twice daily (157 patients) or bosutinib 500 mg once daily (76 patients). In the overall cohort, the median patient age was 52 years (range, 19-83), 51.5% of patients were female sex, 74.7% of patients were White, 80.7% of patients had an Eastern Cooperative Oncology Group performance status of 0, and 48.1% and 31.3% of patients had received 2 and 3 prior therapy lines, respectively. Patients were, stratified by major cytogenetic response (MCyR) status prior to receiving therapy.

After a median follow-up of 14.9 months, the major molecular response rate at 24 weeks was 25.5% in the asciminib group vs 13.2% in the bosutinib group. After adjusting for baseline MCyR status, the difference in response rate was determined to be 12.2% (P =.029).

Patients in the asciminib group were also less likely to have grade 3 or worse adverse events (50.6%) and adverse events leading to therapy discontinuation (5.8%) than were patients in the bosutinib group (60.5% and 21.1%, respectively).

“Overall, the clinically meaningful and statistically significant, superior efficacy of asciminib compared with that of bosutinib, deeper molecular response rates, and favorable safety profile support the potential of asciminib to transform the CML treatment landscape,” the authors wrote. “Our results demonstrate that asciminib, the first STAMP inhibitor, has potential to be the standard of care for [third-] and later-line therapies.”

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Réa D, Mauro MJ, Boquimpani C, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021;138(21):2031-2041. doi:10.1182/blood.2020009984