PMID- 36717654
OWN - NLM
STAT- MEDLINE
DCOM- 20230309
LR  - 20231213
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 37
IP  - 3
DP  - 2023 Mar
TI  - Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously 
      treated with at least two tyrosine kinase inhibitors: longer-term follow-up of 
      ASCEMBL.
PG  - 617-626
LID - 10.1038/s41375-023-01829-9 [doi]
AB  - Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL 
      Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with 
      Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase 
      (CML-CP) treated with >/=2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, 
      patients with CML-CP treated with >/=2 prior TKIs were randomized (stratified by 
      baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or 
      bosutinib 500 mg once daily. Consistent with previously published primary 
      analysis results, after a median follow-up of 2.3 years, asciminib continued to 
      demonstrate superior efficacy and better safety and tolerability than bosutinib. 
      The major molecular response (MMR) rate at week 96 (key secondary endpoint) was 
      37.6% with asciminib vs 15.8% with bosutinib; the MMR rate difference between the 
      arms, after adjusting for baseline MCyR, was 21.7% (95% CI, 10.53-32.95; 
      two-sided p = 0.001). Fewer grade >/=3 adverse events (AEs) (56.4% vs 68.4%) and 
      AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib 
      than with bosutinib. A higher proportion of patients on asciminib than bosutinib 
      remained on treatment and continued to derive benefit over time, supporting 
      asciminib as a standard of care for patients with CML-CP previously treated with 
      >/=2 TKIs.
CI  - (c) 2023. The Author(s).
FAU - Hochhaus, Andreas
AU  - Hochhaus A
AUID- ORCID: 0000-0003-0626-0834
AD  - Universitatsklinikum Jena, Jena, Germany. andreas.hochhaus@med.uni-jena.de.
FAU - Rea, Delphine
AU  - Rea D
AD  - Adult Hematology and INSERM CIC1427, Hopital Saint-Louis, Paris, France.
FAU - Boquimpani, Carla
AU  - Boquimpani C
AD  - HEMORIO, State Institute of Hematology Arthur de Siquiera Cavalcanti, Rio de 
      Janeiro, Brazil.
AD  - Oncoclinica Centro de Tratamento Oncologico, Rio de Janeiro, RJ, Brazil.
FAU - Minami, Yosuke
AU  - Minami Y
AUID- ORCID: 0000-0003-0863-0739
AD  - National Cancer Center Hospital East, Kashiwa, Japan.
FAU - Cortes, Jorge E
AU  - Cortes JE
AUID- ORCID: 0000-0002-8636-1071
AD  - Georgia Cancer Center, Augusta, GA, USA.
FAU - Hughes, Timothy P
AU  - Hughes TP
AD  - South Australian Health and Medical Research Institute and University of 
      Adelaide, Adelaide, SA, Australia.
FAU - Apperley, Jane F
AU  - Apperley JF
AUID- ORCID: 0000-0002-1710-1794
AD  - Centre for Haematology Imperial College London, London, UK.
FAU - Lomaia, Elza
AU  - Lomaia E
AD  - Almazov National Medical Research Centre, St. Petersburg, Russia.
FAU - Voloshin, Sergey
AU  - Voloshin S
AD  - Russian Research Institute of Hematology and Transfusiology, St. Petersburg, 
      Russia.
FAU - Turkina, Anna
AU  - Turkina A
AUID- ORCID: 0000-0001-9947-2371
AD  - National Medical Research Center for Hematology, Moscow, Russia.
FAU - Kim, Dong-Wook
AU  - Kim DW
AD  - Uijeongbu Eulji Medical Center, Geumo-dong, Uijeongbu-si, South Korea.
FAU - Abdo, Andre
AU  - Abdo A
AD  - Instituto do Cancer do Estado de Sao Paulo (ICESPSP), Sao Paulo, Brazil.
FAU - Fogliatto, Laura Maria
AU  - Fogliatto LM
AD  - Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
FAU - le Coutre, Philipp
AU  - le Coutre P
AD  - Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Sasaki, Koji
AU  - Sasaki K
AUID- ORCID: 0000-0002-9140-0610
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Kim, Dennis Dong Hwan
AU  - Kim DDH
AD  - Princess Margaret Cancer Centre, University Health Network, University of 
      Toronto, Toronto, ON, Canada.
FAU - Saussele, Susanne
AU  - Saussele S
AUID- ORCID: 0000-0003-0357-5785
AD  - III. Medizinische Klinik, Medizinische Fakultat Mannheim der Universitat 
      Heidelberg, Mannheim, Germany.
FAU - Annunziata, Mario
AU  - Annunziata M
AD  - Division of Hematology, AORN Cardarelli, Naples, Italy.
FAU - Chaudhri, Naeem
AU  - Chaudhri N
AD  - King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi 
      Arabia.
FAU - Chee, Lynette
AU  - Chee L
AUID- ORCID: 0000-0002-4250-4448
AD  - Peter MacCallum Cancer Center and The Royal Melbourne Hospital, Parkville, VIC, 
      Australia.
FAU - Garcia-Gutierrez, Valentin
AU  - Garcia-Gutierrez V
AUID- ORCID: 0000-0003-4752-0815
AD  - Servicio de Hematologia, Hospital Universitario Ramon y Cajal, Instituto Ramon y 
      Cajal de Investigacion Sanitaria (IRYCIS), Madrid, Spain.
FAU - Kapoor, Shruti
AU  - Kapoor S
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Allepuz, Alex
AU  - Allepuz A
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Quenet, Sara
AU  - Quenet S
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Bedoucha, Veronique
AU  - Bedoucha V
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Mauro, Michael J
AU  - Mauro MJ
AUID- ORCID: 0000-0002-2251-4032
AD  - Memorial Sloan Kettering Cancer Center, New York, NY, USA.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230130
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 5018V4AEZ0 (bosutinib)
RN  - 0 (asciminib)
RN  - 0 (Tyrosine Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Tyrosine Kinase Inhibitors
MH  - Follow-Up Studies
MH  - Treatment Outcome
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - *Leukemia, Myeloid, Chronic-Phase
MH  - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
PMC - PMC9991909
COIS- The authors declare the following potential conflicts of interest: AH received 
      institutional research support from Novartis, Bristol Myers Squibb, Incyte, and 
      Pfizer and personal fees from Novartis and Incyte. DR received personal fees from 
      Novartis, Pfizer, and Incyte. CB received grants from Novartis during the conduct 
      of the study. YM received honoraria from Bristol Myers Squibb, Novartis, Pfizer, 
      and Astellas. JEC received grants and consulting fees from Novartis, grants and 
      consulting fees from Pfizer, and grants from Bristol Myers Squibb. TPH received 
      grants and honoraria for advisory boards and symposia from Novartis and grants 
      from Bristol Myers Squibb. JFA received honoraria, grants, and personal fees from 
      Novartis and grants and personal fees from Pfizer. EL received grants from 
      Novartis and personal fees and non-financial support from Novartis, Pfizer, and 
      Bristol Myers Squibb. SV received personal fees and non-financial support from 
      Novartis, AbbVie, Janssen, Sanofi, and BIOCAD; non-financial support from Pfizer; 
      and personal fees from Takeda and AstraZeneca. AT declares no competing financial 
      interests. D-WK received grants from Novartis, Bristol Myers Squibb, Pfizer, 
      ILYANG, and Takeda. AAbdo received honoraria from Novartis and Takeda. LMF 
      declares no competing financial interests. PlC received speaker's honoraria from 
      Novartis, Incyte, Pfizer, and Bristol Myers Squibb. KS received research funding 
      and honoraria for advisory boards from Novartis. DDHK received grants, honoraria, 
      and consulting fees from Novartis; grants from Bristol Myers Squibb; and 
      honoraria from Pfizer and Paladin. SS received honoraria, grants, and personal 
      fees from Novartis and grants and personal fees from Bristol Myers Squibb and 
      Incyte, and honoraria from Roche and Pfizer. MA declares no competing financial 
      interests. NC declares no competing financial interests. LC received honoraria 
      and participated in advisory boards for Novartis and Otsuka. VG-G received 
      grants, non-financial support, and honoraria from Novartis, Pfizer, Bristol Myers 
      Squibb, and Incyte. SK is an employee of Novartis. AAllepuz is an employee of 
      Novartis. SQ is an employee of Novartis. VB is an employee of Novartis. MJM 
      received personal fees from Bristol Myers Squibb, Takeda, and Pfizer.
EDAT- 2023/01/31 06:00
MHDA- 2023/03/10 06:00
PMCR- 2023/01/30
CRDT- 2023/01/30 23:43
PHST- 2023/01/06 00:00 [received]
PHST- 2023/01/18 00:00 [accepted]
PHST- 2023/01/12 00:00 [revised]
PHST- 2023/01/31 06:00 [pubmed]
PHST- 2023/03/10 06:00 [medline]
PHST- 2023/01/30 23:43 [entrez]
PHST- 2023/01/30 00:00 [pmc-release]
AID - 10.1038/s41375-023-01829-9 [pii]
AID - 1829 [pii]
AID - 10.1038/s41375-023-01829-9 [doi]
PST - ppublish
SO  - Leukemia. 2023 Mar;37(3):617-626. doi: 10.1038/s41375-023-01829-9. Epub 2023 Jan 
      30.