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ASCEMBL Points To STAMP Inhibitor For Previously Treated CML

The first-in-class STAMP inhibitor asciminib increases the likelihood of major molecular response in heavily pretreated chronic myeloid leukaemia patients compared with bosutinib
09 Dec 2020
Anticancer Agents;  Haematological Malignancies;  Leukaemia

Author: By Lynda Williams, Senior medwireNews Reporter 


medwireNews: Chronic myeloid leukaemia (CML) patients who have received at least two lines of tyrosine kinase inhibitor (TKI) therapy may benefit from treatment with the novel agent asciminib, suggest the ASCEMBL trial findings.  

Results for the first-in-class Specifically Targeting the ABL Myristol Pocket (STAMP) inhibitor were reported by Andreas Hochhaus, from Klinik für Innere Medizin II in Jena, Germany, at the virtual 62nd American Society of Hematology Annual Meeting and Exposition. 

“Asciminib demonstrated statistically significant and clinically meaningful, superior efficacy compared with bosutinib and a favorable safety profile”, he commented. 

The trial recruited patients with CML in the chronic phase who had failure or intolerance to their second or later line TKI and were free from the T315I and V299L mutations associated with resistance to the second-generation TKI bosutinib. 

The primary endpoint of major molecular response (MMR) at 24 weeks was achieved by 25.5% of the 157 patients who were randomly assigned to receive asciminib 40 mg twice daily versus 13.2% of the 76 patients who instead were given bosutinib 500 mg/day.  

After adjusting for major cytogenetic response at baseline, there was a significant 12.2 percentage point difference in the 24-week rate of MMR between the treatment arms in favour of asciminib, the presenter said.  

After a median follow-up of 14.9 months, treatment was ongoing in 61.8% of the patients using asciminib versus 30.3% of those given bosutinib, with median durations of treatment being 43.4 and 29.2 weeks, respectively. 

Preplanned analysis suggested that the 24-week MMR rate was higher with asciminib than bosutinib for most patient subgroups. After adjusting for baseline major cytogenetic response, patients given asciminib were 2.35 times more likely to achieve MMR than those given bosutinib. This remained largely unchanged, at an odds ratio of 2.38, after considering patient sex, baseline major cytogenetic response, line of treatment therapy, and reason for discontinuation of the last TKI. 

At 24 weeks, patients given asciminib were more likely than bosutinib-treated patients to have achieved MR4 (10.8 vs 5.3%) and MR4.5 (8.9 vs 1.3%) criteria for deep molecular responses, as well as a complete cytogenetic response (40.8 vs 24.2%). 

The most common reason for discontinuation of asciminib was lack of efficacy (21.0%), physician decision (6.4%) and adverse events (5.1%), while for bosutinib the most common reasons cited were lack of efficacy (31.6%), adverse events (21.1%) and physician decision (7.9%). 

Grade 3 and more severe adverse events occurred in 50.6% of the asciminib arm and 60.5% of the bosutinib arm. These events led to discontinuation in 5.1% and 15.8% of patients, respectively, most commonly for thrombocytopenia and neutropenia with asciminib and liver enzyme increases with bosutinib. 

Arterial occlusive events occurred in 3.2% and 1.3% of the asciminib and bosutinib treatment groups, respectively. 

Andreas Hochhaus reported that newly emerging BCR–ABL1 mutations after asciminib treatment were identified at the ATP binding site and myristoyl binding pocket in two patients each versus none in the bosutinib arm. 

But he emphasized that “conclusions on the impact of mutations cannot be made due to their low incidence and heterogeneity”. 

The presenter concluded: “The ASCEMBL results support the use of asciminib as a new treatment option in CML, particularly in patients with resistance or intolerance to at least two TKIs. 

“BCR-ABL1 remains the key driver of CML even in patients beyond the second-line”, he added. 


Hocchaus A, Boquimpani C, Rea D, et al. LBA-4 Efficacy and safety results from ASCEMBL, a multicenter, open-label, phase 3 study of asciminib, a first-in-class STAMP inhibitor, vs bosutinib in patients with chronic myeloid leukemia in chronic phase previously treated with ≥2 tyrosine kinase inhibitors. 62nd ASH Annual Meeting and Exposition; 5–8 December 2020. 

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group

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