Volume 99, Issue 8 pp. 1576-1585
CRITICAL REVIEW

Ponatinib-review of historical development, current status, and future research

Hagop M. Kantarjian

Corresponding Author

Hagop M. Kantarjian

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Correspondence

Hagop M. Kantarjian, Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 428, Houston, TX 77030, USA.

Email: [email protected]

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Helen T. Chifotides

Helen T. Chifotides

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Fadi G. Haddad

Fadi G. Haddad

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Nicholas J. Short

Nicholas J. Short

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Sanam Loghavi

Sanam Loghavi

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Elias Jabbour

Elias Jabbour

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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First published: 10 May 2024
Citations: 8

Abstract

Ponatinib is a third-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) with high potency against Philadelphia chromosome (Ph)-positive leukemias, including T315I-mutated disease, which is resistant to first- and second-generation TKIs. Ponatinib was approved for T315I-mutated chronic myeloid leukemia (CML), CML resistant/intolerant to ≥2 prior TKIs, advanced phase CML and Ph-positive acute lymphoblastic leukemia (ALL) where no other TKIs are indicated, and T315I-mutated CML and Ph-positive ALL. The response-based dosing of ponatinib in chronic phase CML (CP-CML) improved treatment tolerance and reduced the risk of toxicities, including cardiovascular risks. Ponatinib-based therapy also resulted in significantly better outcomes in frontline Ph-positive ALL compared with prior TKIs and is becoming a new standard of care in this setting. As the clinical development of third-generation TKIs and their rational combinations progresses, we envision further transformative changes in the treatment of CML and Ph-positive ALL.

CONFLICT OF INTEREST STATEMENT

HMK: Research grants from Novartis, Pfizer, Ascentage, Takeda. Honoraria from Novartis, Pfizer, Ascentage, Takeda. NJS: Research grants from Takeda Oncology, GSK, Astellas Pharma Inc., Xencor, Stemline Therapeutics, and NextCure. Consulting fees from Pfizer Inc., GSK, NKARTA, Autolus, and Sanofi. Honoraria from Adaptive Biotechnologies, Novartis, Amgen, Takeda Oncology, Pfizer Inc., Astellas Pharma Inc., Sanofi, and BeiGene. EJ: Research grants and consultancy from Amgen, Adaptive Biotechnologies, Ascentage, Autolus, Bristol-Myers Squibb, Pfizer, Takeda, Novartis, Abbvie, Genentech, ASTX, TGRX, TERN, and Johnson and Johnson. SL: Research: Amgen, Astellas; Consulting/honoraria: Guidepoint, QualWorld, Gerson Lehrman Group, Abbvie, Daiichi Sankyo, BluePrint medicine, Caris Diagnostics, Recordati, Alphasight, Arima, Qiagen, Cogent Biosciences. HTC and FGH report no COIs.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon request.

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