Ponatinib-review of historical development, current status, and future research
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]
Search for more papers by this authorHelen T. Chifotides
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorFadi G. Haddad
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorNicholas J. Short
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorSanam Loghavi
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorElias Jabbour
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorCorresponding 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]
Search for more papers by this authorHelen T. Chifotides
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorFadi G. Haddad
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorNicholas J. Short
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorSanam Loghavi
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorElias Jabbour
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Search for more papers by this authorAbstract
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.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon request.
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