Real-world outcomes in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia treated with ponatinib - final 6-year results from a Belgian registry. - 2025
Real-world outcomes in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia treated with ponatinib - final 6-year results from a Belgian registry.
[en] [en] BACKGROUND: Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) for treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in patients who fail or are intolerant to a second generation TKI or who carry the T315I mutation.
METHOD: This is the final analysis of the Belgian ponatinib registry evaluating use of ponatinib in clinical practice, with data available for up to 6 years after reimbursement.
RESULT: Forty-eight percent of 54 CML and 28% of 29 Ph+ ALL patients had received ≥3 previous TKIs. Before ponatinib, most patients had already achieved a response, including at least a major molecular response (MMR), in 19% of CML and 17% of Ph+ ALL patients. Ponatinib was initiated due to intolerance to previous TKIs in 50% of CML and 41% of Ph+ ALL patients. Median follow-up was 545 and 258 days for CML and Ph+ ALL patients, respectively. Best response to ponatinib was at least an MMR in 65% of CML and 55% of Ph+ ALL patients. Overall and progression-free survival were 85.8% and 83.8% in CML patients after 48 months of treatment, and 82.5% and 54.2% in Ph+ ALL patients after 30 months of treatment. Adverse reactions were reported by 85% of CML and 76% of Ph+ ALL patients, with 33% of CML and 24% of Ph+ ALL patients experiencing cardiovascular events.
CONCLUSION: In line with previously published trials, these real-world data support use of ponatinib in CML and Ph+ ALL patients with resistance or intolerance to previous TKIs or carrying the T315I mutation.Trial registration: ClinicalTrials.gov identifier: NCT03678454; September 19, 2018. [en] What is this study about? Chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) are types of blood cancer.Ponatinib belongs to a group of medicines called tyrosine kinase inhibitors (TKIs). People with CML or Ph+ ALL can use ponatinib if they no longer benefit from or cannot tolerate treatment with at least two previous TKIs, or if their cancer cells have a gene change (or mutation) called T315I.This study looked at people with CML and Ph+ ALL being given ponatinib at Belgian hospitals over 6 years and how they responded to ponatinib treatment.What were the results? Almost 50% of people with CML and 30% of people with Ph+ ALL received treatment with three or more TKIs before ponatinib.Many people started taking ponatinib because they could not tolerate their previous TKI.86% of people with CML were alive after 48 months of ponatinib treatment. The cancer did not get any worse in 84% of people during this time.83% of people with Ph+ ALL were alive after 30 months of ponatinib treatment. The cancer did not get any worse in 54% of people during this time.33% of people with CML and 24% of people with Ph+ ALL experienced cardiovascular side effectsWhat do the results mean? This real-world study shows that people with CML and Ph+ ALL who do not respond to or cannot tolerate another TKI, or who carry the T315I mutation, may benefit from ponatinib treatment and toxicity is generally acceptable.
Disciplines :
Hematology
Author, co-author :
Devos, Timothy ; Department of Hematology, University Hospitals Leuven and Laboratory of Molecular Immunology (Rega Institute), KU Leuven, Leuven, Belgium
Real-world outcomes in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia treated with ponatinib - final 6-year results from a Belgian registry.
This study, medical writing, and publication coordination were supported by research funding from Incyte Biosciences Benelux BV. The authors would like to thank the patients, their caregivers, the clinical investigators, and the research personnel for their contribution to this registry. The authors would also like to thank Tina Van den Meersche for providing medical writing support (Akkodis, Wavre, Belgium on behalf of Incyte Biosciences Benelux BV).
Jabbour E, Kantarjian H., Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol. 2018;93(3):442–459. doi:10.1002/ajh.25011
Yilmaz M, Kantarjian H, Ravandi-Kashani F, et al.Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: current treatments and future perspectives. Clin Adv Hematol Oncol. 2018;16(3):216–223.
Druker BJ., Translation of the Philadelphia chromosome into therapy for CML. Blood. 2008;112(13):4808–4817. doi:10.1182/blood-2008-07-077958
Lipton JH, Bryden P, Sidhu MK, et al.Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors. Leuk Res. 2015;39(1):58–64. doi:10.1016/j.leukres.2014.10.005
Garg RJ, Kantarjian H, O'Brien S, et al.The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up. Blood. 2009;114(20):4361–4368. doi:10.1182/blood-2009-05-221531
Garcia-Gutierrez V, Hernandez-Boluda JC., Tyrosine Kinase Inhibitors Available for Chronic Myeloid Leukemia: Efficacy and Safety. Front Oncol. 2019;9:603. doi:10.3389/fonc.2019.00603
RIZIV. Vergoedbare geneesmiddelen 2023 [updated 2023 Jan 1; accessed 2023 Jan 26]. Available from: https://webappsa.riziv-inami.fgov.be/SSPWebApplicationPublic/nl/Public/ProductSearch
Réa D, Hughes TP., Development of asciminib, a novel allosteric inhibitor of BCR-ABL1. Critical Reviews in Oncology/Hematology. 2022;171:103580. doi:10.1016/j.critrevonc.2022.103580
Cortes JE, Kim DW, Pinilla-Ibarz J, et al.Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132(4):393–404. doi:10.1182/blood-2016-09-739086
European Medicines Agency. Summary of product characteristics 2018. [accessed Oct 10, 2022]. Available from: https://www.ema.europa.eu/en/documents/product-information/iclusig-epar-product-information_en.pdf
Hochhaus A, Baccarani M, Silver RT, et al.European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966–984. doi:10.1038/s41375-020-0776-2
Hochhaus A, Breccia M, Saglio G, et al.Expert opinion–management of chronic myeloid leukemia after resistance to second-generation tyrosine kinase inhibitors. Leukemia. 2020;34(6):1495–1502. doi:10.1038/s41375-020-0842-9
Cortes JE, Kim DW, Pinilla-Ibarz J, et al.A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. The New England Journal of Medicine. 2013;369(19):1783–1796. doi:10.1056/NEJMoa1306494
Etienne G, Rea D, Coiteux V, et al.Ponatinib long-term follow-up of efficacy and safety in CP-CML patients in real world settings in France: The POST-PACE study. Leuk Res. 2021;104:106541. doi:10.1016/j.leukres.2021.106541
Januzzi JL, Garasic JM, Kasner SE, et al.Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee. J Hematol Oncol. 2022;15(1):1. doi:10.1186/s13045-021-01221-z
Cortes J, Apperley J, Lomaia E, et al.Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial. Blood. 2021;138(21):2042–2050. doi:10.1182/blood.2021012082
Devos T, Havelange V, Theunissen K, et al.Clinical outcomes in patients with Philadelphia chromosome-positive leukemia treated with ponatinib in routine clinical practice-data from a Belgian registry. Ann Hematol. 2021;100(7):1723–1732. doi:10.1007/s00277-021-04507-x
Breccia M, Iurlo A, Ferrara F, et al.Multicenter, prospective and retrospective observational cohort study of ponatinib in patients with CML in Italy: Long-term follow-up results of the OITI trial. Frankfurt: European Hematology Association; 2023.
Dorer DJ, Knickerbocker RK, Baccarani M, et al.Impact of dose intensity of ponatinib on selected adverse events: Multivariate analyses from a pooled population of clinical trial patients. Leuk Res. 2016;48:84–91. doi:10.1016/j.leukres.2016.07.007
