COST-EFFECTIVENESS ANALYSIS OF THE SEQUENTIAL APPLICATION OF TYROSINE KINASE INHIBITORS FOR THE TREATMENT OF CHRONIC MYELOID LEUKEMIA

Purpose: The introduction of the tyrosine kinase inhibitor (TKI) imatinib dramatically extended the overall survival of chronic myeloid leukemia (CML) patients. Currently, there are several different TKIs approved for CML therapy. The aim of our study was to evaluate the long-term cost-effectiveness of different therapy regimens for CML within the Austrian health care context.

Methods: We performed a cost-effectiveness analysis using a previously developed state-transition Markov model for patients in the chronic phase of CML treated first-line with imatinib, dasatinib or nilotinib. The model evaluates seven treatment strategies including different combinations of first and second-generation TKIs as well as chemotherapy or stem cell transplantation. For model parameters, we used published trial data, original data from the Austrian CML registry, official Austrian drug prices from the “Warenverzeichnis”, Austrian DRGs, Austrian procedure fees for outpatient services and estimates from Austrian CML experts to parameterize the model. We performed a cohort simulation over a lifelong time horizon. Evaluated outcomes included life expectancy, quality-adjusted life years (QALYs), life-time costs, and discounted incremental cost-effectiveness ratios (ICER). We adopted a societal perspective and a discount rate of 3%. We performed extensive univariate and multivariate (probabilistic) sensitivity analyses as well as a scenario analysis for generic drug pricing of imatinib.

Results: In the base-case efficiency frontier, imatinib followed by nilotinib after failure yielded an ICUR of 131,300 €/QALY and an ICER of 117,000 €/LY compared to the baseline strategy imatinib without second-line TKI treatment after imatinib failure. Nilotinib followed by dasatinib after failure resulted in an ICUR of 163,000 €/QALY and an ICER of 197,800 €/LY compared to imatinib followed by nilotinib after failure. The remaining four strategies were excluded due to absolute or extended dominance. In the scenario analysis for imatinib becoming generic, strategies without imatinib were either dominated or the strategy nilotinib followed by dasatinib resulted in a very high ICER ranging between 480,000 and 670,000 €/QALY.

Conclusions: Our analysis revealed high ICERs for the treatment of CML with TKIs. In Austria, the sequential application of TKIs is standard of care and withholding a second-line TKI would not be acceptable. Therefore, based on our analysis we recommend imatinib followed by nilotinib as the most cost-effective treatment strategy.