Objectives: To estimate the savings and opportunity costs of nilotinib considering treatment free remission after 2nd line treatment of chronic myeloid leukemia (CML) with Nilotinib to fund BCR-ABL molecular test under the Brazilian public healthcare system (SUS) perspective

Materials and methods: A budget impact analysis was developed to estimate the savings for the public health system with TFR eligible patients. ENESTop (Mahon FX et al., 2018), an ongoing, single-arm, phase 2 study is the first trial specifically evaluating treatment-free remission (TFR; ie, stopping tyrosine kinase inhibitor [TKI] treatment without a loss of response) in patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieved a sustained deep molecular response after switching from imatinib to nilotinib. In this trial, patients using nilotinib, who had 4.5 log molecular response after at least 24 months of Nilotinib treatment after switching from imatinib, entered into 12 months of consolidation phase and if they maintain MR 4.5 log response (77%), treatment was discontinued as planned in study protocol (57.9% TFR rate at 48 weeks - primary endpoint).

A systematic review of the literature was developed over the efficacy of the use of nilotinib in 2nd line for patients diagnosed with CML. Efficacy data used to input the economic model is informed in a published randomized controlled clinical trial (ENESTcmr trial, Hughes TP et al., 2015), a 48 month, open-label, randomized, phase 3 study designed to investigate whether patients with complete cytogenetic response but persistent minimal residual disease on long-term imatinib ( ≥ 2 years prior imatinib) could achieve MR 4.5 log response by switching from imatinib to Nilotinib 400 mg BID. In this study, 33%, 42%, 46% and 52% of patients achieved 4.5 log molecular response by 12, 24, 36 and 48 months of nilotinib treatment after switching from imatinib. The total annual cost in 2017 with nilotinib was extracted from an official Brazilian database (http://paineldeprecos.planejamento.gov.br).

Results: Considering that MR 4.5 log response patients will start consolidation in the first year, the economic impact will reduce in BRL 7,2M in the second year year, reaching a saving of BRL 11,4M in the fifth year. The total accumulated saving for the Brazilian public system (SUS) in 5-years was over BRL 38,1M. We also evaluated the necessary investments on BCR-ABL monitoring tests for all CML patients in the public market, as this test is not reimbursed by Brazilian public healthcare system (SUS). We estimated a budget impact of BRL 4.5M per year considering an average of 2 monitoring tests per patient, thus in 5 years an investment of 22,5M in BCR-ABL would be necessary.

Discussion: The deep molecular response (MR 4.5 log) in may lead to patient discontinuation in those patients achieving 4.5 log molecular response after at least 24 months of nilotinib treatment and maintaining this response after 12 months. Furthermore, the possibility of TFR with nilotinib will save resources in health sytems allowing to invest in other needs. As demonstrated in this study, savings generated by nilotinib in 2nd line considering the possibility of TFR could allow the incorporation of BCR-ABL test for all CML patients in the public health system (SUS), which is essential in the current management of CML.

Conclusion: Nilotinib in 2nd line treatment may generate savings for the public healthcare system (SUS) that could fund the BCR-ABL test for all CML patients.


Vivona:Novartis: Employment. Leite:Novartis: Employment. Matsuo:Novartis: Employment. Teich:Novartis: Consultancy.

Author notes


Asterisk with author names denotes non-ASH members.