Cost-Effectiveness of Therapeutic Drug Monitoring for Imatinib Administration in Patients with Chronic Myeloid Leukemia
Authors: Kim Kibum , McMillin Gwendolyn A. , Bernard Philip S. , Tantravahi Srinivas K. , Walker Brandon , Schmidt Robert L 
Published: October 2019

Abstract
Background: Generic imatinib mesylate (IM) is an effective therapy and is the least costly tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) has the potential to improve the adherence to IM therapy as well as helps oncologists to make an informed decision. This eventually leads a delayed switching to 2ndor 3rdgeneration (2G or 3G) TKIs that dramatically increase the treatment cost. The objective of this study was to determine the short- and lifetime cost-effectiveness of TDM for generic IM administration in patients newly diagnosed with CML.
Methods: We built a Markov model to compare CML related healthcare costs, quality adjusted life years (QALY), incremental cost-effectiveness ratio (ICER) and overall survival (OS) between the two monitoring strategies, TDM vs. standard care without TDM (NTDM). Future cost and QALY gained were discounted with an annual rate of 3%. Markov states for chronic phase include normal IM dose (400mg), IM dose escalation (600mg), IM dose reduction (300mg), 2GTKI, 3GTKI. Post TKI phases include accelerate phase, blast phase and post-transplant phase with an assumption that patients need 3GTKI along with a chemotherapy until they receive hematopoietic stem cell transplant. Outcome of this study was an incremental cost effectiveness ratio (ICER). A potential reason for the response or intolerance to IM was informed by a known plasma concentration (Cp) from the TDM arm, that helps a treatment decision between the IM dose change and switching to 2GTKI. In the NTDM arm, response and intolerance rate was influenced by Cp, but clinical decision was blinded from the Cp. The outcomes were calculated over the initial 5 years and accumulated until all patients die. The influence of a changes in generic IM price were tested.
Results: Over the initial 5 years, TDM was associated with a drop in the cost (- $6,510) with a trivial decrease in QALY (-0.007) compared to NTDM. The cost-saving continued over the 30 years after the TKI therapy begins. TDM resulted in a lifetime cost increased by $2,358, which was associated with a delayed progress to the post-TKI phases and treatment cost over the extended life years gained. TDM leads an increase in lifetime QALY by 0.149, calculating an ICER of $15,834. When the cost of generic IM further dropped to the 50% of the current whole-sale price, TDM saves the lifetime cost by $11,705. Ten-year survival rates and median OS favored TDM (87.1% and 19.5 years) over NTDM (86.4% and 19 years).
Conclusion: TDM has a potential to save the medical expenses for CML care over the first 5 years without influences after the TKI treatment begins. When current generic price maintained, TDM is a cost-effective strategy over a lifetime. Addition drop in the generic IM price could lead a saving in the CML care cost with a gain in the QALY over the lifetime.

Disclosures
No relevant conflicts of interest to declare.