Cost-Effectiveness of Ponatinib in The Treatment of Patients with Acute Lymphoblastic Leukemia with Philadelphia Chromosome Positive (PH+ ALL), Suitable for Allogeneic Stem Cell Transplant, in Greece

To evaluate the cost-effectiveness of ponatinib over induction chemotherapy (IC), for the treatment of patients with Acute Lymphoblastic Leukemia with Philadelphia chromosome positive (Ph+ ALL) who exhibit resistance or intolerance (R/I) to dasatinib, or have the T315I mutation and are suitable for allogeneic stem cell transplant (allo-SCT), in Greece. An international Markov model with 3-month cycles was locally adapted from a third-party payer perspective (EOPYY) to reflect the natural progression of patients with Ph+ ALL through different health states over a life-time horizon (50-years). Clinical data for ponatinib arm were retrieved from phase II trial (PACE), whereas for IC arm from LALA-94 trial. In the absence of valuations for Ph+ ALL health states, utilities for blast phase chronic-myeloid-leukemia were used. Resource use for the management of Ph+ ALL patients as well as the distribution of IC schemes used in Greece were based on experts' opinion. The relevant unit costs were obtained from local resources (prices €2017). Outcomes were evaluated in terms of life-years (LY) and quality-adjusted life-years (QALYs), and cost-effectiveness in terms of life-years gained (LYG) and QALYs gained. One-way (OWSA) and probabilistic sensitivity analysis (PSA) were conducted. Patients treated with ponatinib had 0.833 higher life expectancy (3.621 versus 2.788 LY) and gained 0.501 QALYs (2.234 versus 1.733) compared to IC, at an increased cost of €5,465 (€40,743 versus €35,277) per patient. The resulted incremental cost-effectiveness ratios were €6,563/LYG and €10,903/QALY gained. OWSA revealed that treatment costs were the drivers of the results, while the PSA showed that the probability of ponatinib to be cost-effective over IC exceeds that of 97% (willingness-to-pay:€51,000). Given the assumptions of this analysis, our results suggest ponatinib may offer improved survival and health related quality-of-life to patients with Ph+ ALL R/I to dasatinib, suitable for allo-SCT, at a moderate increase in cost compared to IC.