TY - JOUR
T1 - CML-395 Efficacy and Safety Results From ASCEMBL, a Phase III Study of Asciminib vs. Bosutinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) After ≥2 Prior Tyrosine Kinase Inhibitors (TKIs)
T2 - Week 96 Update
AU - Réa, Delphine
AU - Hochhaus, Andreas
AU - Mauro, Michael J.
AU - Minami, Yosuke
AU - Lomaia, Elza
AU - Voloshin, Sergey
AU - Turkina, Anna
AU - Kim, Dong Wook
AU - Apperley, Jane F.
AU - Cortes, Jorge E.
AU - Abdo, Andre
AU - Fogliatto, Laura Marie
AU - Kim, Dennis Dong Hwan
AU - Coutre, Philipp le
AU - Saussele, Susanne
AU - Annunziata, Mario
AU - Hughes, Timothy P.
AU - Chaudhri, Naeem
AU - Chee, Lynette
AU - García-Gutiérrez, Valentin
AU - Sasaki, Koji
AU - Kapoor, Shruti
AU - Allepuz, Alex
AU - Quenet, Sara
AU - Bédoucha, Véronique
AU - Boquimpani, Carla
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10
Y1 - 2022/10
N2 - Context: Asciminib is the first BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, among patients with CML-CP after ≥2 prior TKIs, asciminib resulted in improved major molecular response (MMR, 25.5% vs. 13.2%) at week 24 and fewer grade ≥3 adverse events (AEs) or AEs leading to treatment discontinuations compared with bosutinib. After a median follow-up of 2.3 years, we report updated efficacy and safety results (data cutoff: October 6, 2021). Objective: To compare the MMR rate at week 96 with asciminib vs. bosutinib. Design: A phase III, multicenter, open-label study of adults with CML-CP after ≥2 prior TKIs randomized 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily and stratified by baseline major cytogenetic response (MCyR). Results: In total, 233 patients were randomized to receive asciminib (n=157) or bosutinib (n=76). At data cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) patients, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) patients, respectively. The key secondary objective was met; MMR rate at week 96 was higher with asciminib (37.6%) than with bosutinib (15.8%). The difference after adjusting for MCyR was 21.7% (95% CI, 10.5%–33.0%; 2-sided P=.001). At week 96, more patients receiving asciminib than bosutinib had BCR::ABL1IS ≤1% (45.1% vs. 19.4%). Responses were durable, with a probabilities (95% CI) of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 weeks of 96.7% (87.4%–99.2%) and 94.6% (86.2%–97.9%), respectively, with asciminib and 92.9% (59.1%–99.0%) and 95.0% (69.5%–99.3%), respectively, with bosutinib. Median time to treatment failure was 24 months with asciminib and 6 months with bosutinib. Asciminib had longer duration of exposure (103.1 vs. 30.5 weeks) but fewer AEs leading to treatment discontinuation (7.7% vs. 26.3%) than bosutinib. Conclusions: After >2 years of follow-up, asciminib demonstrated durable responses by continuing to show superior efficacy and better safety/tolerability vs. bosutinib. MMR more than doubled with asciminib over bosutinib, and the difference in MMR rates increased between the 2 arms from 12.2% at week 24 to 21.7% at week 96. These results support the use of asciminib as a new CML therapy.
AB - Context: Asciminib is the first BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP). In the ASCEMBL primary analysis, among patients with CML-CP after ≥2 prior TKIs, asciminib resulted in improved major molecular response (MMR, 25.5% vs. 13.2%) at week 24 and fewer grade ≥3 adverse events (AEs) or AEs leading to treatment discontinuations compared with bosutinib. After a median follow-up of 2.3 years, we report updated efficacy and safety results (data cutoff: October 6, 2021). Objective: To compare the MMR rate at week 96 with asciminib vs. bosutinib. Design: A phase III, multicenter, open-label study of adults with CML-CP after ≥2 prior TKIs randomized 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily and stratified by baseline major cytogenetic response (MCyR). Results: In total, 233 patients were randomized to receive asciminib (n=157) or bosutinib (n=76). At data cutoff, treatment was ongoing in 84 (53.5%) and 15 (19.7%) patients, respectively; the most common reason for discontinuation was lack of efficacy in 38 (24.2%) and 27 (35.5%) patients, respectively. The key secondary objective was met; MMR rate at week 96 was higher with asciminib (37.6%) than with bosutinib (15.8%). The difference after adjusting for MCyR was 21.7% (95% CI, 10.5%–33.0%; 2-sided P=.001). At week 96, more patients receiving asciminib than bosutinib had BCR::ABL1IS ≤1% (45.1% vs. 19.4%). Responses were durable, with a probabilities (95% CI) of maintaining MMR and BCR::ABL1IS ≤1% for ≥72 weeks of 96.7% (87.4%–99.2%) and 94.6% (86.2%–97.9%), respectively, with asciminib and 92.9% (59.1%–99.0%) and 95.0% (69.5%–99.3%), respectively, with bosutinib. Median time to treatment failure was 24 months with asciminib and 6 months with bosutinib. Asciminib had longer duration of exposure (103.1 vs. 30.5 weeks) but fewer AEs leading to treatment discontinuation (7.7% vs. 26.3%) than bosutinib. Conclusions: After >2 years of follow-up, asciminib demonstrated durable responses by continuing to show superior efficacy and better safety/tolerability vs. bosutinib. MMR more than doubled with asciminib over bosutinib, and the difference in MMR rates increased between the 2 arms from 12.2% at week 24 to 21.7% at week 96. These results support the use of asciminib as a new CML therapy.
KW - ASCEMBL
KW - CML
KW - Phase III
KW - TKI
KW - Trial-in-Progress
KW - asciminib
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U2 - 10.1016/S2152-2650(22)01379-9
DO - 10.1016/S2152-2650(22)01379-9
M3 - Article
C2 - 36163925
AN - SCOPUS:85138189670
SN - 2152-2650
VL - 22
SP - S295-S296
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -
