Asciminib add-on to imatinib demonstrates sustained high rates
of ongoing therapy and deep molecular responses with prolonged
follow-up in the ASC4MORE study

J 2024

Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study

HUGHES, Timothy P; Giuseppe SAGLIO; Jan GEISSLER; Dong-Wook KIM; Elza LOMAIA et. al.

Basic information

Original name

Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study

Authors

HUGHES, Timothy P; Giuseppe SAGLIO; Jan GEISSLER; Dong-Wook KIM; Elza LOMAIA; Jiří MAYER (203 Czech Republic, belonging to the institution); Anna TURKINA; Shruti KAPOOR; Ana Paula CARDOSO; Becki NIEMAN; Sara QUENET and Jorge E CORTES

Edition

JOURNAL OF HEMATOLOGY & ONCOLOGY, LONDON, BMC, 2024, 1756-8722

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 29.900 in 2023

RIV identification code

RIV/00216224:14110/24:00138584

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1186/s13045-024-01642-6

UT WoS

001380081200004

EID Scopus

2-s2.0-85212503824

Keywords in English

ASC4MORE; CML; Asciminib; Tyrosine kinase inhibitors; Deep molecular response; Imatinib; Add-on; Combination

Abstract

V originále

BackgroundUp to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy. The phase II ASC4MORE trial investigated the strategy of adding asciminib to imatinib in patients who have not achieved deep molecular response with imatinib.MethodsIn ASC4MORE, 84 patients with CML in chronic phase not achieving deep molecular response after >= 1 year of imatinib therapy were randomized to asciminib 40 or 60 mg once daily (QD) add-on to imatinib 400 mg QD, continued imatinib 400 mg QD, or switch to nilotinib 300 mg twice daily.ResultsMore patients in the asciminib 40- and 60-mg QD add-on arms (19.0% and 28.6%, respectively) achieved MR4.5 (BCR::ABL1 <= 0.0032% on the International Scale) at week 48 (primary endpoint) than patients in the continued imatinib (0.0%) and switch to nilotinib (4.8%) arms. Fewer patients discontinued asciminib 40- and 60-mg QD add-on treatment (14.3% and 23.8%, respectively) than imatinib (76.2%, including crossover patients) and nilotinib (47.6%). Asciminib add-on was tolerable, with rates of AEs and AEs leading to discontinuation less than those with nilotinib, although higher than those with continued imatinib (as expected in these patients who had already been tolerating imatinib for >= 1 year). No new or worsening safety signals were observed with asciminib add-on vs the known asciminib monotherapy safety profile.ConclusionsOverall, these results support asciminib add-on as a treatment strategy to help patients with CML in chronic phase stay on therapy to safely achieve rapid and deep response, although further investigation is needed before this strategy is incorporated into clinical practice.Trial registrationNCT03578367

Cite

HUGHES, Timothy P; Giuseppe SAGLIO; Jan GEISSLER; Dong-Wook KIM; Elza LOMAIA; Jiří MAYER; Anna TURKINA; Shruti KAPOOR; Ana Paula CARDOSO; Becki NIEMAN; Sara QUENET and Jorge E CORTES. Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study. JOURNAL OF HEMATOLOGY & ONCOLOGY. LONDON: BMC, 2024, vol. 17, No 1, p. 1-12. ISSN 1756-8722. Available from: https://dx.doi.org/10.1186/s13045-024-01642-6.

@article{2470280,
   author = {Hughes, Timothy P and Saglio, Giuseppe and Geissler, Jan and Kim, DongandWook and Lomaia, Elza and Mayer, Jiří and Turkina, Anna and Kapoor, Shruti and Cardoso, Ana Paula and Nieman, Becki and Quenet, Sara and Cortes, Jorge E},
   article_location = {LONDON},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s13045-024-01642-6},
   keywords = {ASC4MORE; CML; Asciminib; Tyrosine kinase inhibitors; Deep molecular response; Imatinib; Add-on; Combination},
   language = {eng},
   issn = {1756-8722},
   journal = {JOURNAL OF HEMATOLOGY & ONCOLOGY},
   title = {Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study},
   url = {https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01642-6},
   volume = {17},
   year = {2024}
}

TY  - JOUR
ID  - 2470280
AU  - Hughes, Timothy P - Saglio, Giuseppe - Geissler, Jan - Kim, Dong-Wook - Lomaia, Elza - Mayer, Jiří - Turkina, Anna - Kapoor, Shruti - Cardoso, Ana Paula - Nieman, Becki - Quenet, Sara - Cortes, Jorge E
PY  - 2024
TI  - Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study
JF  - JOURNAL OF HEMATOLOGY & ONCOLOGY
VL  - 17
IS  - 1
SP  - 1-12
EP  - 1-12
PB  - BMC
SN  - 17568722
KW  - ASC4MORE
KW  - CML
KW  - Asciminib
KW  - Tyrosine kinase inhibitors
KW  - Deep molecular response
KW  - Imatinib
KW  - Add-on
KW  - Combination
UR  - https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01642-6
N2  - BackgroundUp to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy. The phase II ASC4MORE trial investigated the strategy of adding asciminib to imatinib in patients who have not achieved deep molecular response with imatinib.MethodsIn ASC4MORE, 84 patients with CML in chronic phase not achieving deep molecular response after >= 1 year of imatinib therapy were randomized to asciminib 40 or 60 mg once daily (QD) add-on to imatinib 400 mg QD, continued imatinib 400 mg QD, or switch to nilotinib 300 mg twice daily.ResultsMore patients in the asciminib 40- and 60-mg QD add-on arms (19.0% and 28.6%, respectively) achieved MR4.5 (BCR::ABL1 <= 0.0032% on the International Scale) at week 48 (primary endpoint) than patients in the continued imatinib (0.0%) and switch to nilotinib (4.8%) arms. Fewer patients discontinued asciminib 40- and 60-mg QD add-on treatment (14.3% and 23.8%, respectively) than imatinib (76.2%, including crossover patients) and nilotinib (47.6%). Asciminib add-on was tolerable, with rates of AEs and AEs leading to discontinuation less than those with nilotinib, although higher than those with continued imatinib (as expected in these patients who had already been tolerating imatinib for >= 1 year). No new or worsening safety signals were observed with asciminib add-on vs the known asciminib monotherapy safety profile.ConclusionsOverall, these results support asciminib add-on as a treatment strategy to help patients with CML in chronic phase stay on therapy to safely achieve rapid and deep response, although further investigation is needed before this strategy is incorporated into clinical practice.Trial registrationNCT03578367
ER  -

HUGHES, Timothy P; Giuseppe SAGLIO; Jan GEISSLER; Dong-Wook KIM; Elza LOMAIA; Jiří MAYER; Anna TURKINA; Shruti KAPOOR; Ana Paula CARDOSO; Becki NIEMAN; Sara QUENET and Jorge E CORTES. Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study. \textit{JOURNAL OF HEMATOLOGY \&{} ONCOLOGY}. LONDON: BMC, 2024, vol.~17, No~1, p.~1-12. ISSN~1756-8722. Available from: https://dx.doi.org/10.1186/s13045-024-01642-6.

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