Budget Impact analysis of the first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) adult patients

Francesco Mennini, Andrea Marcellusi, Raffaella Viti, Giuseppe Saglio

DOI: https://doi.org/10.7175/fe.v18i1.1318


Background: Tyrosine kinase inhibitors (TKI) have dramatically improved survival in chronic myeloid leukemia in chronic phase (CML‐CP), with a high percentage of patients reaching a major molecular response (MMR). Recently, several clinical trials demonstrated that some patients with CML-CP who achieve a sustained MMR on tyrosine kinase inhibitor (TKI) therapy can safely discontinue their therapy and attempt treatment-free remission (TFR).
Objective: The aim of the study was to evaluate the clinical and economic impact of TFR in naïve patients with CML-CP who start treatment with nilotinib, imatinib or dasatinib as first-line therapy, from the perspective of the Italian National Health Service (NHS).
Methods: An Excel-based budget impact model was developed, in order to estimate the costs of the patients in first-line pharmacological treatment with CML. A specific Markov model was built, to simulate seven years of treatment with different TKIs. A systematic literature review was carried out, to identify the epidemiological and economic data, which were subsequently used to inform the model. The model considers two scenarios: 1) a Standard of Care (SoC) scenario, with the current estimated distribution of patients over the various TKI treatment, versus 2) an innovative scenario, characterized by an increase in the use of nilotinib (+28%) and generic imatinib (+35%) and a decrease in the use of dasatinib (-17%). A one-way deterministic sensitivity analysis was performed, in order to consider the variability of the results as a function of the main parameters considered in the model.
Results: The model estimated that 775 patients with CML-CP could be treated with a TKI as first-line drug. The innovative scenario could increase TFR patients by approximately 60% and reduce the costs by more than € 30 million over 7 years. The increase in the use of nilotinib and the generic imatinib would generate a significant expenditure reduction.
Conclusions: This study demonstrates the economic effects of discontinuing TKIs in CML-CP patients. The increase in the use of nilotinib and the generic imatinib could generate an increase in the number of patients who achieve TFR, as well as an actual cost reduction.


Tyrosine kinase inhibitors; Chronic myeloid leukemia; Budget Impact Model; Treatment-free remission

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  • Jabbour EJ, Hughes TP, Cortés JE, et al. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia. Leuk Lymphoma 2014; 55: 1451-62; https://doi.org/10.3109/10428194.2013.845883
  • Faderl S, Talpaz M, Estrov Z, et al. The biology of chronic myeloid leukemia. N Engl J Med 1999; 341: 164-72; https://doi.org/10.1056/NEJM199907153410306
  • Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring. Am J Hematol 2016; 91: 252-65; https://doi.org/10.1002/ajh.24275
  • Lucioni C, Iannazzo S, Mazzi S, et al. Valutazione di costo-efficacia di ponatinib nella terapia della leucemia mieloide cronica in Italia. Global & Regional Health Technology Assessment 2015; 2: 1-16
  • Hehlmann R, Müller MC, Lauseker M, et al. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. J Clin Oncol 2014; 32: 415-23; https://doi.org/10.1200/JCO.2013.49.9020
  • Larson RA, Hochhaus A, Hughes TP, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 2012; 26: 2197-203; https://doi.org/10.1038/leu.2012.134
  • Hochhaus A, Masszi T, Giles FJ, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia 2017; 31: 1525-31; https://doi.org/10.1038/leu.2017.63
  • Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood 2014; 123: 494-500; https://doi.org/10.1182/blood-2013-06-511592
  • Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013; 122: 872-84; https://doi.org/10.1182/blood-2013-05-501569
  • Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia. Leucemia Mieloide Cronica. Available at: http://www.ematologia-pavia.it/it/patologie/leucemia-mieloide-cronica/ (last accessed March 2017)
  • Ross D, Masszi T, Gómez Casares MT, et al. Durable Treatment-Free Remission (Tfr) Following Frontline Nilotinib (Nil) In Patients (Pts) With Chronic Myeloid Leukemia In Chronic Phase (Cml-Cp): Enestfreedom 96-Wk Update. 22nd Congress of the European Hematology Association (EHA). Madrid, June 22-25, 2017. Abstract: P601. Available at: https://learningcenter.ehaweb.org/eha/2017/22nd/181888/david.ross.durable.treatment-free.remission.28tfr29.following.frontline.html?f=m2e1181l15532 (last accessed July 2017)
  • Mauskopf JA, Sullivan SD, Annemans L, et al. Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices--budget impact analysis. Value Health 2007; 10: 336-47; https://doi.org/10.1111/j.1524-4733.2007.00187.x
  • Sullivan SD, Mauskopf JA, Augustovski F, et al. Budget impact analysis-principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force. Value Health 2014; 17: 5-14; https://doi.org/10.1016/j.jval.2013.08.2291
  • Istituto Nazionale di Statistica (ISTAT). Popolazione residente al 1 Gennaio 2014. Statistiche Demografiche 2015. Available at: http://demo.istat.it/ (last accessed March 2017)
  • Siebert U, Alagoz O, Bayoumi AM, et al.; ISPOR-SMDM Modeling Good Research Practices Task Force. State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force--3. Value Health 2012; 15: 812-20; https://doi.org/10.1016/j.jval.2012.06.014
  • Prezzi massimi acquisti SSN. AIFA Ufficio Prezzi e Rimborso 23/01/2015. Available at http://www.aslbrescia.it/media/documenti/cure_primarie/anno%202015/Farmacisti/Farmaci/PREZZI%20MASSIMI%20ACQUISTI%20SSN_23_1_2015.pdf (last accessed March 2017)
  • Informatore Farmaceutico on-line. Available at: http://www.codifa.it/ (last accessed March 2017)
  • AIFA – Agenzia Italiana del Farmaco. Liste di trasparenza e rimborsabilità. Available at: http://www.agenziafarmaco.gov.it/content/liste-di-trasparenza-e-rimborsabilit%C3%A0 (last accessed March 2017)
  • Hochhaus A, Masszi T, Gile FJ, et al. Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline nilotinib: Results from the ENESTFreedom study. J Clin Oncol 2016; 34 (15_suppl): 7001
  • Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia 2016; 30: 1044-54; https://doi.org/10.1038/leu.2016.5


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