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This study was sponsored and funded by Novartis Pharmaceuticals.

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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

Publicated to:LEUKEMIA. 37 (5): 1048-1059 - 2023-03-22 37(5), DOI: 10.1038/s41375-023-01860-w

Authors: Mauro, MJ; Hughes, TP; Kim, DW; Rea, D; Cortes, JE; Hochhaus, A; Sasaki, K; Breccia, M; Talpaz, M; Ottmann, O; Minami, H; Goh, YT; DeAngelo, DJ; Heinrich, MC; de Soria, VGG; le Coutre, P; Mahon, FX; Janssen, JJWM; Deininger, M; Shanmuganathan, N; Geyer, MB; Cacciatore, S; Polydoros, F; Agrawal, N; Hoch, M; Lang, FB

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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 approximate to 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.

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