J 2024

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia

HOCHHAUS, Andreas, Jianxiang WANG, Dong-Wook KIM, Dennis Dong Hwan KIM, Jiří MAYER et. al.

Basic information

Original name

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia

Authors

HOCHHAUS, Andreas, Jianxiang WANG, Dong-Wook KIM, Dennis Dong Hwan KIM, Jiří MAYER, Yeow-Tee GOH, le Coutre PHILIPP, Naoto TAKAHASHI, Inho KIM, Gabriel ETIENNE, David ANDORSKY, Ghayas C ISSA, Richard A LARSON, Felice BOMBACI, Shruti KAPOOR, Tracey MCCULLOCH, Kamel MALEK, Lillian YAU, Sophie IFRAH, Matthias HOCH, Jorge E CORTES and Timothy P HUGHES

Edition

New England Journal of Medicine, Waltham, Massachussetts Medical Society, 2024, 0028-4793

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 158.500 in 2022

Organization unit

Faculty of Medicine

DOI

UT WoS

001236416200001

Keywords in English

Chronic Myeloid Leukemia; Asciminib

Tags

Tags

International impact, Reviewed
Změněno: 20/8/2024 11:59, Mgr. Tereza Miškechová

Abstract

V originále

Background Patients with newly diagnosed chronic myeloid leukemia (CML) need long-term therapy with high efficacy and safety. Asciminib, a BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket, may offer better efficacy and safety and fewer side effects than currently available frontline ATP-competitive tyrosine kinase inhibitors (TKIs). Methods In a phase 3 trial, patients with newly diagnosed CML were randomly assigned in a 1:1 ratio to receive either asciminib (80 mg once daily) or an investigator-selected TKI, with randomization stratified by European Treatment and Outcome Study long-term survival score category (low, intermediate, or high risk) and by TKI selected by investigators before randomization (including imatinib and second-generation TKIs). The primary end points were major molecular response (defined as BCR::ABL1 transcript levels <= 0.1% on the International Scale [IS]) at week 48, for comparisons between asciminib and investigator-selected TKIs and between asciminib and investigator-selected TKIs in the prerandomization-selected imatinib stratum. Results A total of 201 patients were assigned to receive asciminib and 204 to receive investigator-selected TKIs. The median follow-up was 16.3 months in the asciminib group and 15.7 months in the investigator-selected TKI group. A major molecular response at week 48 occurred in 67.7% of patients in the asciminib group, as compared with 49.0% in the investigator-selected TKI group (difference, 18.9 percentage points; 95% confidence interval [CI], 9.6 to 28.2; adjusted two-sided P<0.001]), and in 69.3% of patients in the asciminib group as compared with 40.2% in the imatinib group within the imatinib stratum (difference, 29.6 percentage points; 95% CI, 16.9 to 42.2; adjusted two-sided P<0.001). The percentage of patients with a major molecular response at week 48 was 66.0% with asciminib and 57.8% with TKIs in the second-generation TKI stratum (difference, 8.2 percentage points; 95% CI, -5.1 to 21.5). Adverse events of grade 3 or higher and events leading to discontinuation of the trial regimen were less frequent with asciminib (38.0% and 4.5%, respectively) than with imatinib (44.4% and 11.1%) and second-generation TKIs (54.9% and 9.8%). Conclusions In this trial comparing asciminib with investigator-selected TKIs and imatinib, asciminib showed superior efficacy and a favorable safety profile in patients with newly diagnosed chronic-phase CML. Direct comparison between asciminib and second-generation TKIs was not a primary objective.