Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results

Mauro, Michael J., Hughes, Timothy P., Kim, Dong-Wook, Rea, Delphine, Cortes, Jorge E., Hochhaus, Andreas, Sasaki, Koji, Breccia, Massimo, Talpaz, Moshe, Ottmann, Oliver ORCID: https://orcid.org/0000-0001-9559-1330, Minami, Hironobu, Goh, Yeow Tee, DeAngelo, Daniel J., Heinrich, Michael C., Gómez-García de Soria, Valle, le Coutre, Philipp, Mahon, Francois-Xavier, Janssen, Jeroen J. W. M., Deininger, Michael, Shanmuganathan, Naranie, Geyer, Mark B., Cacciatore, Silvia, Polydoros, Fotis, Agrawal, Nithya, Hoch, Matthias and Lang, Fabian 2023. Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results. Leukemia 37 , pp. 1048-1059. 10.1038/s41375-023-01860-w

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Abstract

Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10–200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6% of patients remained on asciminib. The most common grade ≥3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1 ≤ 1%, 61.6% achieved ≤0.1% (major molecular response [MMR]), and 33.7% achieved ≤0.01% on the International Scale. MMR was maintained in 48/53 patients who achieved it and 19/20 who were in MMR at screening, supporting the long-term safety and efficacy of asciminib in this population.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	0887-6924
Date of First Compliant Deposit:	30 March 2023
Date of Acceptance:	21 February 2023
Last Modified:	06 Jun 2023 22:36
URI:	https://orca.cardiff.ac.uk/id/eprint/158182

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