S155: Efficacy and Safety Results From Ascembl, a Phase 3 Study of Asciminib vs Bosutinib in Patients With Chronic Myeloid Leukemia in Chronic Phase After ≥2 Prior Tyrosine Kinase Inhibitors: Wk 96 Update

Abstract

Background:Background: Asciminib is the 1st BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, asciminib had superior efficacy and better safety/tolerability vs bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs). Major molecular response (MMR) rate at wk 24 was 25.5% on asciminib vs 13.2% on BOS; the difference in MMR rates after adjusting for baseline major cytogenetic response (MCyR) was 12.2% (95% CI, 2.19%-22.30%; 2sided P=.029). Fewer grade ≥3 adverse events (AEs) and AEs leading to treatment discontinuation occurred on asciminib vs BOS. After a median follow-up of 2.3 years (16.5 months' additional follow-up since the primary analysis), we report updated efficacy and safety results (cutoff: October 6, 2021). Aims: Aims:The key secondary objective was to compare MMR rate at wk 96 on asciminib vs BOS. Methods:Methods: Eligible pts provided informed consent, were adults with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 European LeukemiaNet recommendations. They were randomized 2:1 to asciminib 40 mg twice daily or BOS 500 mg once daily, stratified by baseline MCyR status (Ph+ metaphases ≤35%). Results:Results: 233 pts were randomized to asciminib (n=157) or BOS (n=76). At cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) pts, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) pts, respectively. MMR rate at wk 96 (per ITT) was 37.6% on asciminib and 15.8% on BOS, meeting the key secondary objective. The difference after adjusting for baseline MCyR was 21.7% (95% CI, 10.5%-33.0%; 2-sided P=.001). Preplanned subgroup analyses showed that MMR rate at wk 96 was consistently higher with asciminib than BOS in all

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

“…An updated analysis of the study at the European Hematology Association (EHA) 2022 annual meeting confirmed the persistent improvement of MMR at 2 years (2‐year MMR rate 38% with asciminib vs. 16% with bosutinib). However, this did not translate into improved PFS (2‐year PFS 94% vs. 91%) or improved survival (2‐year survival 97% vs. 99%) 118 …”

“…Among patients with T315I vs. 99%). 118 Asciminib was also approved for patients with T315I mutation based on a separate report, where 52 patients with CML-CP and T315I mutation who failed ≥2 prior TKIs received asciminib 200 mg twice daily (31 patients had prior ponatinib exposure, of whom 15 had ponatinib resistance). 119 The estimated 2-year MMR rate was 57.8% in the ponatinib-naïve patients and 28.6% in ponatinib-treated patients.…”

The outcomes of patients with chronic myeloid leukemia treated with third‐line BCR::ABL1 tyrosine kinase inhibitors

“…Asciminib is another TKI recently approved for patients who have failed two TKIs or more, based on higher response rates in comparison with bosutinib, with overall 6‐month MMR rates of 26% versus 13% and cumulative 2‐year MMR rates of 38% and 16%, respectively, after a median follow‐up of 2.3 years 15,16 . However, in the third‐line setting, no difference was seen in the rate of MMR at 12 months between asciminib and bosutinib (31% versus 27%) 25 .…”

“…Other options available as third‐line therapy include the third‐generation BCR::ABL1 TKIs like ponatinib, the novel third‐generation TKIs like asciminib and the investigational TKI olverembatinib 13–15 . Asciminib was approved in 2021 for third‐line therapy of CML‐CP, based on a randomized trial comparing it with bosutinib, which showed a higher rate or major molecular response (MMR; BCR::ABL1 transcript levels <0.1% by the International Scale [IS]) with asciminib (6‐month MMR 25% versus 11.9%) 15,16 …”

“…[13][14][15] Asciminib was approved in 2021 for third-line therapy of CML-CP, based on a randomized trial comparing it with bosutinib, which showed a higher rate or major molecular response (MMR; BCR::ABL1 transcript levels <0.1% by the International Scale [IS]) with asciminib (6-month MMR 25% versus 11.9%). 15,16 Ponatinib is a potent third-generation BCR::ABL1 TKI with activity against the ABL1 T315I mutation. 17 In the PACE trial, ponatinib was evaluated in a multiple relapsed/refractory population (≥3 prior TKIs in 60%, and resistance to prior dasatinib or nilotinib in 84%) and showed significant efficacy in this setting.…”