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 Journal Article
| Authors: | Mauro, M. J.; Hughes, T. P.; Kim, D. W.; Rea, D.; Cortes, J. E.; Hochhaus, A.; Sasaki, K.; Breccia, M.; Talpaz, M.; Ottmann, O.; Minami, H.; Goh, Y. T.; DeAngelo, D. J.; Heinrich, M. C.; Gómez-García de Soria, V.; le Coutre, P.; Mahon, F. X.; Janssen, J. J. W. M.; Deininger, M.; Shanmuganathan, N.; Geyer, M. B.; Cacciatore, S.; Polydoros, F.; Agrawal, N.; Hoch, M.; Lang, F. |
| Article Title: | 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 |
| 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. [Figure not available: see fulltext.]. © 2023, The Author(s). |
| Keywords: | adult; controlled study; gene mutation; major clinical study; genetics; mutation; clinical trial; constipation; drug tolerability; fatigue; neutropenia; diarrhea; drug efficacy; drug safety; hypertension; monotherapy; side effect; antineoplastic agents; cancer patient; antineoplastic agent; gene; edema; anemia; protein kinase inhibitor; nausea; thrombocytopenia; vomiting; drug resistance; drug resistance, neoplasm; chronic myeloid leukemia; protein tyrosine kinase inhibitor; arthralgia; coughing; dizziness; dyspnea; fever; hyperglycemia; pruritus; rash; protein kinase inhibitors; insomnia; depression; disease severity; thorax pain; pancreatitis; drug response; rating scale; open study; dyslipidemia; pancreas enzyme; headache; bcr abl protein; phase 1 clinical trial; liver enzyme; dry eye; leukemia, myelogenous, chronic, bcr-abl positive; fusion proteins, bcr-abl; upper respiratory tract infection; hyperhidrosis; antileukemic activity; decreased appetite; enzyme blood level; artery occlusion; musculoskeletal pain; major molecular response; lower respiratory tract infection; humans; human; male; female; article; oropharynx pain; body weight gain; asciminib; abl1 gene; bcr gene; international scale |
| Journal Title: | Leukemia |
| Volume: | 37 |
| Issue: | 5 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-05-01 |
| Start Page: | 1048 |
| End Page: | 1059 |
| Language: | English |
| DOI: | 10.1038/s41375-023-01860-w |
| PUBMED: | 36949155 |
| PROVIDER: | scopus |
| PMCID: | PMC10169635 |
| DOI/URL: | |
| Notes: | Article -- MSK corresponding author is Michael Mauro -- Source: Scopus |
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