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

Abstract

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.

Budget Impact of Treatment-Free Remission in Treating Chronic-Phase Philadelphia-Positive Chronic Myeloid Leukemia in Lebanon

“…Effective strategies such as TKI discontinuation are needed to allow shifting from a constant accumulation of cost of treating CML to an economic plateau and stable costs. 30-32 The savings that TFR can offer can compensate the cost of treating patients with newly diagnosed disease.…”

Economic Model to Evaluate the Cost-Effectiveness of Second-Line Nilotinib Versus Dasatinib for the Treatment of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia (CML-CP) in Italy

“…Based on the costs and the frequencies of AEs for both treatments, nilotinib had a slightly lower calculated per-patient cost of managing grade 3 and 4 AEs than dasatinib (5.32 € vs 7.92 €). End-of-life costs were assumed to be 8010.81 €, which is in line with the estimate for cost of death due to disease from previous Italian economic analyses for TKIs in CML [13,36].…”

“…Hematologist visits were assumed to occur monthly in all health states at a fee of 21.22 €/visit [36]. BCR-ABL monitoring (208.49 €/test) was assumed to occur once every 3 months in all health states, except TFR, where it was assumed to occur monthly [7,13,36].…”

“…With survival of CML patients approaching that of the general population, long-term TKI treatment can lead to budgetary pressures that could be alleviated through TFR and treatment discontinuation [12]. Indeed, recent budget impact analyses estimated that TFR could reduce total CML treatment costs in Italy by more than 54 million euros over 7 years [13], in Lebanon by more than $7 million (USD) over 4 years [14], and in Japan by over $66 million (USD) over 3 years [15]. Cost-effectiveness analyses (CEAs) are also now demonstrating the impact of TFR in increasing quality-adjusted life-years (QALYs) and decreasing costs in first-line treatment of patients with CML with TKIs [16,17], yet consideration for TFR in CEAs of second-line treatment of CML has not been shown.…”

GL-V9 induce apoptosis of CML cells via MAPK signaling pathway

“…The genetic rearrangement leads to the creation of the BCR-ABL fusion gene, which is functionally an oncogene [ 3 , 4 ]. The Philadelphia Chromosome (Ph), a reciprocal translocation of chromosome 9 and chromosome 22 [ 5 ], is very commonly found in patients with CML, accounting for approximately 90 % of CML cases [ 6 , 7 ]. Its presence is not only a key diagnostic marker for CML but also plays a crucial role in the treatment of the disease [ 8 ].…”