CHRONIC MYELOID LEUKEMIA TREATMENT: STARTING WITH A HIGHLY POTENT TYROSINE KINASE INHIBITOR AND EARLY SWITCHING TO IMATINIB?

Purpose :   To identify the optimal sequential treatment strategy in terms of clinical effectiveness and cost effectiveness for chronic phase chronic myeloid leukemia (CML) patients in Austria dependent on early molecular response (EMR).

Method :   We adapted and extended a previously developed decision-analytic model to incorporate different treatment options (imatinib, dasatinib, nilotinib; no dose increase) dependent on achievement of EMR after 3 months. We analyzed eight different sequential treatment strategies (Figure 1). The model was developed as a Markov state-transition model and analyzed as a cohort simulation over a lifelong time horizon. Model parameters were extracted from clinical trials, epidemiological databases, published literature and economic data from official Austrian catalogues. We applied a 3% discount for both health outcomes and costs. We analyzed 3 different base-case scenarios for patients not achieving an EMR after 3-month imatinib treatment. These patients were switched to a second-generation TKI and scenarios A (highest effectiveness), B and C (lowest effectiveness) assumed different effectiveness for these second-generation TKIs. Several deterministic sensitivity and scenario analyses were conducted.

Result :   Scenario B of the base-case analysis resulted in two non-dominated strategies: (1) imatinib, followed by nilotinib in case of non-achieved EMR at 3 months and dasatinib after treatment failure or imatinib continuation in case of achieved 3-month EMR and nilotinib after treatment failure; (2) nilotinib followed by its continuation in case of non-achieved EMR at 3 months or switch to imatinib in case of achieved 3 month EMR and dasatinib after treatment failure. Strategy 2 resulted in an incremental cost-effectiveness ratio (ICER) of €118,500/QALY gained compared to the baseline strategy. All remaining strategies were excluded due to dominance. Scenario analyses A and C resulted in the same two non-dominated strategies with an ICER of 142,200/QALY (A) and 84,200/QALY (C) Sensitivity analyses on generic pricing of imatinib showed that starting with a more potent second-generation TKI and switching to imatinib after an achieved EMR are the preferred strategies.

Conclusion :   Authors suggest nilotinib and its continuation in case of non-achieved EMR at 3 months or switch to imatinib in case of achieved 3-month EMR and dasatinib after treatment failure as a cost-effective treatment strategy for Austria if the willingness-to pay threshold is at least €118,500/QALY. Our model results may guide further decision making on early treatment switches.