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We report updated phase I results (NCT02081378) assessing safety\/tolerability and antileukemic activity of asciminib monotherapy 200\u2009mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years\u2019 median exposure, 56.3% of patients continued receiving asciminib. Overall, 62.2% of evaluable patients achieved <jats:italic>BCR::ABL1<\/jats:italic>\u2009\u22641% on the International Scale (IS); 47.6% and 81.3% of ponatinib-pretreated and -naive patients, respectively, achieved <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup>\u2009\u22641%. Of 45 evaluable patients, 48.9% achieved a major molecular response (MMR, <jats:italic>BCR::ABL1<\/jats:italic><jats:sup>IS<\/jats:sup>\u2009\u22640.1%), including 34.6% and 68.4% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade \u22653 adverse events (AEs) included increased lipase level (18.8%) and thrombocytopenia (14.6%). Five (10.4%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib\u2019s effectiveness, including in almost 50% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.<\/jats:p>","DOI":"10.1038\/s41375-024-02278-8","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T19:01:53Z","timestamp":1715886113000},"page":"1522-1533","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after \u22651 prior tyrosine kinase inhibitor: 2-year follow-up results"],"prefix":"10.1038","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-1071","authenticated-orcid":false,"given":"Jorge E.","family":"Cortes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9140-0610","authenticated-orcid":false,"given":"Koji","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Wook","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0910-3730","authenticated-orcid":false,"given":"Timothy P.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Etienne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2251-4032","authenticated-orcid":false,"given":"Michael J.","family":"Mauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0626-0834","authenticated-orcid":false,"given":"Andreas","family":"Hochhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-0478","authenticated-orcid":false,"given":"Michael C.","family":"Heinrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-6162","authenticated-orcid":false,"given":"Massimo","family":"Breccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-1331","authenticated-orcid":false,"given":"Michael","family":"Deininger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-0997","authenticated-orcid":false,"given":"Yeow Tee","family":"Goh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J.W.M.","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Talpaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valle Gomez Garcia","family":"de Soria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"le Coutre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-2306","authenticated-orcid":false,"given":"Daniel J.","family":"DeAngelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Damon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cacciatore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotis","family":"Polydoros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4279-8324","authenticated-orcid":false,"given":"Nithya","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Rea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"2278_CR1","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","volume":"34","author":"A Hochhaus","year":"2020","unstructured":"Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. 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KS <i>Novartis<\/i>: research funding, honoraria. D-WK <i>Novartis<\/i>, <i>Bristol Myers Squibb<\/i>, <i>Pfizer<\/i>, <i>IL-YANG<\/i>, and <i>Takeda<\/i>: grants. TPH <i>Novartis<\/i>, <i>Bristol Myers Squibb<\/i>, and <i>Enliven<\/i>: consultancy, research funding. GE <i>BMS<\/i>, <i>Incyte Biosciences<\/i>, <i>Novartis<\/i>, and <i>Pfizer<\/i>: speaker. MJM <i>Bristol Myers Squibb<\/i>, <i>Takeda<\/i>, and <i>Pfizer<\/i>: personal fees. AH <i>Bristol Myers Squibb<\/i>, <i>Pfizer<\/i>: institutional research support; <i>Novartis<\/i> and <i>Incyte<\/i>: institutional research support, personal fees. FL <i>Bristol Myers Squibb<\/i>, <i>Incyte<\/i>, and <i>Celgene<\/i>: consultancy, honoraria; <i>Novartis<\/i>: consultancy, honoraria, and research funding. MCH <i>Novartis<\/i>, <i>Deciphera<\/i>, <i>Theseus<\/i>, and <i>Blueprint Medicines<\/i>: consultancy; <i>Deciphera<\/i>: speaker\u2019s bureau; <i>Jonathan David Foundation<\/i>, <i>VA Merit Review Grant (I01BX005358)<\/i>, and <i>NCI R21 grant (R21CA263400):<\/i> partial salary support. Prior to 2019, MCH held an equity interest in <i>MolecularMD<\/i>. MCH holds multiple patents on the diagnosis and\/or treatment of gastrointestinal stromal tumors; one patent on treatment has been licensed by <i>Oregon Health & Science University<\/i> to <i>Novartis<\/i>. MB <i>Bristol Myers Squibb<\/i>, <i>Celgene<\/i>, <i>Pfizer<\/i>, <i>Incyte<\/i>, and <i>Novartis<\/i>: consultancy and honoraria; <i>AbbVie<\/i>: consultancy. MD <i>Fusion Pharma<\/i>, <i>Blueprint<\/i>, <i>Pfizer<\/i>, <i>Novartis<\/i>, <i>Medscape<\/i>, and <i>Sangamo<\/i>: consultancy; <i>Pfizer<\/i>: research funding; <i>Takeda<\/i>, <i>Sangamo<\/i>, and <i>Blueprint<\/i>: membership on board of directors or advisory committees. YTG <i>Pfizer<\/i>, <i>Johnson & Johnson<\/i>, <i>Amgen<\/i>, <i>MSD Pharma<\/i>, <i>Novartis<\/i>, <i>EUSA Pharma<\/i>, <i>Roche<\/i>, <i>Bristol Myers Squibb<\/i>, and <i>AbbVie<\/i>: honoraria. JJWMJ <i>Novartis<\/i> and <i>Bristol Myers Squibb<\/i>: research funding; <i>Incyte<\/i>: speaker\u2019s fee; <i>AbbVie<\/i>, <i>Novartis<\/i>, <i>Pfizer<\/i>, and <i>Incyte<\/i>: honoraria; <i>AbbVie<\/i>, <i>Alexion<\/i>, <i>Amgen<\/i>, <i>Astellas<\/i>, <i>Bristol Myers Squibb<\/i>, <i>Daiichi Sankyo<\/i>, <i>Janssen-Cilag<\/i>, <i>Olympus<\/i>, <i>Incyte<\/i>, <i>Sanofi Genzyme<\/i>, <i>Servier<\/i>, <i>Jazz<\/i>, and <i>Takeda<\/i>: support for <i>Apps for Care and Science<\/i> nonprofit foundation of which J.J.W.M.J. is president. MT <i>IMAGO<\/i>: consultancy; <i>Novartis<\/i> and <i>Takeda<\/i>: research funding; <i>Constellation Pharmaceuticals<\/i> and <i>Bristol Myers Squibb<\/i>: membership on board of directors or advisory committees. VGGS <i>Novartis<\/i>, <i>Pfizer<\/i>, <i>Bristol Myers Squibb<\/i>, and <i>Incyte<\/i>: grants, nonfinancial support, and honoraria. PC <i>Pfizer<\/i>, <i>Novartis<\/i>, and <i>Incyte<\/i>: honoraria. DJD <i>AbbVie<\/i>, <i>Novartis<\/i>, <i>Blueprint<\/i>, and <i>GlycoMimetics<\/i>: grants; <i>AbbVie<\/i>, <i>Novartis<\/i>, <i>Blueprint<\/i>, and <i>GlycoMimetics<\/i>: research funding; <i>AbbVie<\/i>, <i>Amgen<\/i>, <i>Autolus<\/i>, <i>Blueprint<\/i>, <i>Forty-Seven<\/i>, <i>GlycoMimetics<\/i>, <i>Incyte<\/i>, <i>Jazz<\/i>, <i>Kite<\/i>, <i>Novartis<\/i>, <i>Pfizer<\/i>, <i>Servier<\/i>, and <i>Takeda<\/i>; consulting. <i>AbbVie<\/i>, <i>Amgen<\/i>, <i>Autolus<\/i>, <i>Blueprint<\/i>, <i>Forty-Seven<\/i>, <i>GlycoMimetics<\/i>, <i>Incyte<\/i>, <i>Jazz<\/i>, <i>Kite<\/i>, <i>Novartis<\/i>, <i>Pfizer<\/i>, <i>Servier<\/i>, and <i>Takeda<\/i>: personal fees. AD, SC, FP, and NA are employees of <i>Novartis<\/i>. DR <i>Novartis<\/i>, <i>Pfizer<\/i>, and <i>Incyte<\/i>: personal fees.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The protocol was approved by the sites\u2019 institutional review boards and\/or ethics committees. The study was conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice Guidelines of the International Conference on Harmonization. All patients provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}