{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T06:11:10Z","timestamp":1759471870032,"version":"build-2065373602"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to evaluate the efficacy of Olverembatinib in patients with relapsed and persistent minimal residual disease-positive Philadelphia chromosome-positive acute lymphoblastic leukemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective analysis of clinical characteristics in 22 patients diagnosed with Ph\u202f+\u202fALL at Qilu Hospital of Shandong University and Yantai Yuhuangding Hospital between December 2018 and December 2024.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A cohort of 22 patients with Ph\u202f+\u202fALL was enrolled in this study. Among them, 12 (54.5%) patients had relapsed Ph\u202f+\u202fALL, while the remaining 10 patients exhibited persistent MRD positivity. In the relapsed subgroup, the CR rate following one treatment cycle reached 75.0% (9\/12), with MRD-negative and MMR rates of 75.0% (9\/12) and 50.0% (6\/12), respectively. Upon completion of two treatment cycles in evaluable patients (<jats:italic>n<\/jats:italic>\u202f=\u202f8), the CR, MRD-negative, and MMR rates all rose to 87.5, 87.5 and 87.5%, respectively. The patients with forfeited MMR on first or second-generation TKIs, of which the MMR rate was restored to 60.0% (6\/10) after one cycle of Olverembatinib treatment, and a pleasant surprise was that their MMR rate soared to 90% (9\/10) after two cycles of Olverembatinib treatment. 70% of them subsequently underwent successful hematopoietic stem cell transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The efficacy and tolerability of Olverembatinib were confirmed in patients with relapsed, MRD-positive, Ph\u202f+\u202fALL, offering a novel therapeutic approach for these patients and making prolonged survival possible.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1662512","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T05:30:49Z","timestamp":1759469449000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of the third-generation tyrosine kinase inhibitor Olverembatinib in relapsed and persistent minimal residual disease positive Philadelphia chromosome-positive acute lymphoblastic leukemia patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Xinwen","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minran","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingli","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1056\/NEJMra2113347","article-title":"Philadelphia 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disease","volume":"205","author":"Liu","year":"2024","journal-title":"Br J Haematol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"5395","DOI":"10.1182\/bloodadvances.2022007764","article-title":"Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia","volume":"6","author":"Ribera","year":"2022","journal-title":"Blood Adv"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1182\/blood-2016-09-739086","article-title":"Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial","volume":"132","author":"Cortes","year":"2018","journal-title":"Blood"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1182\/blood-2023-187744","article-title":"Update of Olverembatinib (HQP1351) overcoming Ponatinib and\/or Asciminib resistance in patients (pts) with heavily pretreated\/refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL)","volume":"142","author":"Jabbour","year":"2023","journal-title":"Blood"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1097\/cad.0000000000001455","article-title":"Novel third-generation tyrosine kinase inhibitor for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a case study","volume":"34","author":"Tan","year":"2023","journal-title":"Anti-Cancer Drugs"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1080\/10428194.2023.2197534","article-title":"Olverembatinib in relapsed Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia: a study of 5 cases","volume":"64","author":"Liu","year":"2023","journal-title":"Leuk Lymphoma"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.clml.2023.04.012","article-title":"Olverembatinib treatment in pediatric patients with relapsed 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transplantation","volume":"100","author":"Zhang","year":"2025","journal-title":"Am J Hematol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1038\/s41375-025-02674-8","article-title":"Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial","volume":"39","author":"Gong","year":"2025","journal-title":"Leukemia"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e35832","DOI":"10.1002\/cncr.35832","article-title":"Olverembatinib in chronic myeloid leukemia-review of historical development, current status, and future research","volume":"131","author":"Kantarjian","year":"2025","journal-title":"Cancer"}],"container-title":["Frontiers in 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