Budget Impact analysis of ponatinib for the management of patients with chronic myeloid leukemia


  • Michele Basile Università Cattolica del Sacro Cuore (UCSC), Facoltà di Economica, Sede di Roma and Alta Scuola di Economia e Management dei Sistemi Sanitari (ALTEMS), Roma - Italy
  • Filippo Rumi Università Cattolica del Sacro Cuore (UCSC), Facoltà di Economica, Sede di Roma and Alta Scuola di Economia e Management dei Sistemi Sanitari (ALTEMS), Roma - Italy
  • Americo Cicchetti Università Cattolica del Sacro Cuore (UCSC), Facoltà di Economica, Sede di Roma and Alta Scuola di Economia e Management dei Sistemi Sanitari (ALTEMS), Roma - Italy




Budget Impact Analysis, Chronic myeloid leukemia, Disease management, Economic evaluation, Ponatinib, TKI


Background: The current clinical practice for patients affected by chronic myeloid leukemia (CML) is based on the evaluation of second generation alternatives following therapeutic failure that leads to a lengthening of patients’ management times and a consequent negative impact in terms of quality of life.

Objective: To determine the economic absorption of resources associated to the management of patients with CML in a scenario in which an early recourse to ponatinib is considered as compared with a scenario based on the current Italian clinical practice characterized by a cyclical recourse to the available therapies.

Methods: A Budget Impact model was developed to compare the resources absorbed in the scenarios under assessment considering a 3-year time horizon and the perspective of the Italian National Health Service. Results are expressed in terms of differential resources absorbed in the alternative scenarios.

Results: The increase in the recourse to ponatinib allowed a saving of resources for the Italian NHS over the 3-year time horizon of –€ 1,979,322 (€ 825,104,350 vs € 823,125,028). The parameter affecting the most of the results achieved in the base-case is the monthly cost of bosutinib used as a third-line treatment.

Conclusions: The increase in the recourse to ponatinib in patients affected by CML that failed to respond to a previous pharmacological therapy resulted to be associated to a lower level of resources’ absorption in the Italian NHS allowing to re-allocate health founds to other fields of the care sector ensuring greater sustainability of the system.


Download data is not yet available.


Tura S, Baccarani M, Zaccaria A. Chronic myeloid leukemia. Haematologica. 1986;71(3):169-176. PMID:3093318

Melo JV, Hughes TP, Apperley JF. Chronic myeloid leukemia. Hematology (Am Soc Hematol Educ Program). 2003;2003(1):132-152. https://doi.org/10.1182/asheducation-2003.1.132PMID:14633780

Cortes JE, Talpaz M, Kantarjian H. Chronic myelogenous leukemia: a review. Am J Med. 1996;100(5):555-570. https://doi.org/10.1016/S0002-9343(96)00061-7 PMID:8644769

Cortes J, Kantarjian H. Advanced-phase chronic myeloid leukemia. Semin Hematol. 2003;40(1):79-86. https://doi.org/10.1016/S0037-1963(03)70045-6 PMID:12563614

Deininger M, O'Brien SG, Guilhot F, et al. International Randomized Study of Interferon Vs STI571 (IRIS) 8-Year Follow up: Sustained Survival and Low Risk for Progression or Events in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib. ASH Annual Meeting Abstracts. 2009;114:1126. https://ashpublications.org/blood/article/114/22/1126/110074/International-Randomized-Study-of-Interferon-Vs

Radich J. Stem cell transplant for chronic myeloid leukemia in the imatinib era. Semin Hematol. 2010;47(4):354-361. https://doi.org/10.1053/j.seminhematol.2010.06.008 PMID:20875552

Druker BJ. Perspectives on the development of imatinib and the future of cancer research. Nat Med. 2009;15(10):1149-1152. https://doi.org/10.1038/nm1009-1149 PMID:19812576

O'Brien SG, Guilhot F, Larson RA, et al; IRIS Investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348(11):994-1004. https://doi.org/10.1056/NEJMoa022457 PMID:12637609

O'Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007;110(7):2242-2249. https://doi.org/10.1182/blood-2007-03-066936 PMID:17496200

Radich JP. The Biology of CML blast crisis. Hematology (Am Soc Hematol Educ Program). 2007;2007(1):384-391. https://doi.org/10.1182/asheducation-2007.1.384 PMID:18024655

Fava C, Kantarjian HM, Jabbour E, et al. Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase. Blood. 2009;113(21):5058-5063. https://doi.org/10.1182/blood-2008-10-184960PMID:19282457

Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354(24):2542-2551. https://doi.org/10.1056/NEJMoa055104 PMID:16775235

le Coutre PD, Giles FJ, Hochhaus A, et al. Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. Leukemia. 2012;26(6):1189-1194. https://doi.org/10.1038/leu.2011.323 PMID:22076466

Doggrell SA. BMS-354825: a novel drug with potential for the treatment of imatinib-resistant chronic myeloid leukaemia. Expert Opin Investig Drugs. 2005;14(1):89-91. https://doi.org/10.1517/13543784.14.1.89 PMID:15709925

Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354(24):2531-2541. https://doi.org/10.1056/NEJMoa055229 PMID:16775234

Shah NP, Kantarjian HM, Kim DW, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008;26(19):3204-3212. https://doi.org/10.1200/JCO.2007.14.9260 PMID:18541900

Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260-2270. https://doi.org/10.1056/NEJMoa1002315 PMID:20525995

Cortes JE, Khoury HJ, Kantarjian HM, et al. Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. Am J Hematol. 2016;91(12):1206-1214. https://doi.org/10.1002/ajh.24536 PMID:27531525

Kantarjian HM, Cortes JE, Kim DW, et al. Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. Blood. 2014;123(9):1309-1318. https://doi.org/10.1182/blood-2013-07-513937 PMID:24345751

O'Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16(5):401-412. https://doi.org/10.1016/j.ccr.2009.09.028 PMID:19878872

Cortes JE, Kim DW, Pinilla-Ibarz J, et al; PACE Investigators. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369(19):1783-1796. https://doi.org/10.1056/NEJMoa1306494 PMID:24180494

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. https://doi.org/10.1016/j.leukres.2016.07.007 PMID:27505637

Jabbour E, Cortes JE, Kantarjian HM. Suboptimal response to or failure of imatinib treatment for chronic myeloid leukemia: what is the optimal strategy? Mayo Clin Proc. 2009;84(2):161-169. https://doi.org/10.4065/84.2.161 PMID:19181650

Hanfstein B, Muller MC, Hehlmann R, et al; SAKK; German CML Study Group. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012;26(9):2096-2102. https://doi.org/10.1038/leu.2012.85 PMID:22446502

Marin D, Ibrahim AR, Lucas C, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol. 2012;30(3):232-238. https://doi.org/10.1200/JCO.2011.38.6565 PMID:22067393

Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872-884. https://doi.org/10.1182/blood-2013-05-501569 PMID:23803709

Jabbour E, Kantarjian H, Cortes J. Chronic myeloid leukemia and second-generation tyrosine kinase inhibitors: when, how, and which one? Semin Hematol. 2010;47(4):344-353. https://doi.org/10.1053/j.seminhematol.2010.06.002 PMID:20875551

Rosti G, Castagnetti F, Gugliotta G, Baccarani M. Tyrosine kinase inhibitors in chronic myeloid leukaemia: which, when, for whom? Nat Rev Clin Oncol. 2017;14(3):141-154. https://doi.org/10.1038/nrclinonc.2016.139 PMID:27752053

Mahon FX, Rea D, Guilhot J, et al; Intergroupe Francais des Leucemies Myeloides Chroniques. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11(11):1029-1035. https://doi.org/10.1016/S1470-2045(10)70233-3 PMID:20965785

Hoffmann VS, Baccarani M, Hasford J, et al. Treatment and outcome of 2904 CML patients from the EUTOS population-based registry. Leukemia. 2017;31(3):593-601. https://doi.org/10.1038/leu.2016.246 PMID:27568522

J Live Tracker - CML & ALL - MediMix Database.

Therapy KnowlEDGE: International Epidemiological Tool.

Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966-984. https://doi.org/10.1038/s41375-020-0776-2 PMID:32127639

Bassan R, Rossi G, Pogliani EM, et al. Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. J Clin Oncol. 2010;28(22):3644-3652. https://doi.org/10.1200/JCO.2010.28.1287 PMID:20606084

Ravandi F, Othus M, O'Brien SM, et al. US intergroup study of chemotherapy plus dasatinib and allogeneic stem cell transplant in Philadelphia chromosome positive ALL. Blood Adv. 2016;1(3):250-259. https://doi.org/10.1182/bloodadvances.2016001495 PMID:29046900

Istituto Italiano di Statistica (ISTAT); Disponibile Online http://dati.istat.it/Index.aspx?DataSetCode=DCIS_POPRES1

Ministero della Salute - Tariffario delle prestazioni di assistenza per acuti. Disponibile Online http://www.salute.gov.it/portale/temi/p2_6.jsp?lingua=italiano&id=3662&area=programmazioneSanitariaLea&menu=vuoto

Ministero della Salute. Disponibile Online http://www.salute.gov.it/portale/temi/p2_6.jsp?id=1767&area=programmazioneSanitariaLea&menu=lea

Agenzia Italiana del Farmaco (AIFA) - Liste di trasparenza Agenzia Italiana del Farmaco (AIFA). Disponibile Online http://www.aifa.gov.it/search/luceneapi_node/lista%20di%20trasparenza

Lucioni C, Iannazzo S. Mazzi S, Saporiti G, Chiroli S. Cost-effectiveness of ponatinib in chronic myeloid leukemia in Italy. Global & Regional Health Technology Assessment, 2015; 2(1):1-16. https://doi.org/10.33393/grhta.2015.320

Mughal TI, Schrieber A. Principal long-term adverse effects of imatinib in patients with chronic myeloid leukemia in chronic phase. Biologics. 2010;4:315-323. https://doi.org/10.2147/BTT.S5775 PMID:21209726

Additional Files



How to Cite

Basile, M., Rumi, F., & Cicchetti, A. (2021). Budget Impact analysis of ponatinib for the management of patients with chronic myeloid leukemia. Global and Regional Health Technology Assessment, 8(1), 87–95. https://doi.org/10.33393/grhta.2021.2238



Original Research Articles


Received 2021-01-30
Accepted 2021-06-28
Published 2021-07-17


Most read articles by the same author(s)

1 2 > >>