Molecular Milestones and Survival Outcomes of Ponatinib Treatment in Patients With Chronic Myeloid Leukemia and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: A Real-World Analysis

Tai-Chung Tseng¹, Yu-Sung Chang¹, Xavier Cheng-Hong Tsai¹, Ming-En Lin², Feng-Ming Tien², Huai-Hsuan Huang¹, Yun-Chu Lin³, Jia-Hau Liu³, Ming-Chih Liu⁴, Chien-Chin Lin⁵, Chieh-Lung Cheng¹, Szu-Chun Hsu⁵, Ming Yao⁶, Mei-Hsuan Tseng⁷, Yen-Ling Peng¹, Bor-Sheng Ko⁸, Yung-Li Yang⁹, Shiann-Tarng Jou¹⁰, Hsin-An Hou¹¹, Wen-Chien Chou¹

Affiliations

¹ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
³ Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
⁴ Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁶ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Division of Cell Therapy, Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁷ Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Tai-Chen Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
⁸ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Tai-Chen Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
⁹ Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹⁰ Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹¹ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Division of General Medicine, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: hsinanhou@ntu.edu.tw.

PMID: 41027807
DOI: 10.1016/j.clml.2025.09.003

Molecular Milestones and Survival Outcomes of Ponatinib Treatment in Patients With Chronic Myeloid Leukemia and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: A Real-World Analysis

Tai-Chung Tseng et al. Clin Lymphoma Myeloma Leuk. 2025.

. 2025 Sep 2:S2152-2650(25)02893-9.

doi: 10.1016/j.clml.2025.09.003. Online ahead of print.

Authors

Affiliations

¹ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
³ Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
⁴ Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁶ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Division of Cell Therapy, Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁷ Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Tai-Chen Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
⁸ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Tai-Chen Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
⁹ Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹⁰ Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹¹ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Division of General Medicine, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: hsinanhou@ntu.edu.tw.

PMID: 41027807
DOI: 10.1016/j.clml.2025.09.003

Abstract

Background: Ponatinib, a third-generation tyrosine kinase inhibitor, has demonstrated its activity against chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, real-world data, particularly in Asian populations, remain limited.

Methods: Patients with CML or Ph+ ALL treated with ponatinib in Taiwan between March 2013 and November 2024 were retrospectively collected. Molecular and cytogenetic data, efficacy outcomes (complete hematologic response [CHR], molecular response [MR], progression-free survival [PFS], overall survival [OS]), and adverse events were analyzed.

Results: Among 52 patients (27 CML and 25 Ph+ ALL; median follow-up: 50.7 months), 94% received ponatinib due to relapsed or refractory disease. Among patients without prior CHR, 89% reached CHR at 12 months. Among patients without prior MR, 57% had MR2.0, 53% MR3.0, and 26% MR5.0 at 12 months. MR2.0 at 6 months and MR3.0 at 12 months correlated with improved outcome in patients with CML. Additional chromosomal abnormalities (ACAs) were identified in 36% of patients and were associated with inferior survival, whereas kinase domain mutations in 78% of studied patients, including T315I (57%), did not affect the outcome. MR3.0 at any time predicted superior OS and PFS in patients with CML, and MR5.0 with superior PFS in patients with Ph+ ALL. One patient (1.9%) had an arterial occlusive event.

Conclusion: Ponatinib demonstrated substantial real-world efficacy in pretreated patients with CML and Ph+ ALL, with MR3.0 in CML and MR5.0 in Ph+ ALL emerging as favorable prognostic markers. In contrast, the presence of ACAs was associated with shorter survival.

Keywords: Adverse events; BCR::ABL1-positive leukemia; Molecular response.

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Conflict of interest statement

Disclosure Hou HA: Honorarium/Travel/Consultancy (BMS, Novartis, Otsuka); Research support (BMS). XCH Tsai: Honorarium (BMS/Novartis/Otsuka); Consultancy (Novartis); Research support (BMS). This work was partially supported by grants from Ministry of Science and Technology (Taiwan) (MOST 104–2314-B-002–128-MY4, 106-2314-B-002-226-MY3, 108-2628-B-002-015, 109-2314-B-002-213, and 111-2314-B-002-279), the Ministry of Health and Welfare (Taiwan) (MOHW 107-TDU-B-211-114009 and 111-TDU-B-221-114001), and the National Key Area International Cooperation Alliance: University Academic Alliance in Taiwan (UAAT) - Kyushu-Okinawa Open University (KOOU) - Medicine and Life Sciences Integrative Program, promoting international collaboration in advanced research. The written informed consent was obtained from the participants in accordance to the Declaration of Helsinki.

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Molecular Milestones and Survival Outcomes of Ponatinib Treatment in Patients With Chronic Myeloid Leukemia and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: A Real-World Analysis

Affiliations

Molecular Milestones and Survival Outcomes of Ponatinib Treatment in Patients With Chronic Myeloid Leukemia and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: A Real-World Analysis

Authors

Affiliations

Abstract

Conflict of interest statement

LinkOut - more resources

Full Text Sources

Miscellaneous