The Cost-Effectiveness of Therapeutic Drug Monitoring (TDM) of Generic Imatinib for the Treatment of Chronic Myelogenous Leukemia

INTRODUCTION: A recent clinical study of using therapeutic drug monitoring (TDM) of imatinib mesylate (IM) for the treatment of chronic myelogenous leukemia (CML) found that the cytogenetic response at 12 months was significantly improved with IM TDM (Rousselot, P. et al. Blood 2015 126:133).Given that tyrosine kinase inhibitors (TKI) other than IM had previously shown more rapid molecular responses at standard doses, the improved IM efficacy using TDM provides new clinical information when selecting a CML treatment.

A recent cost-effectiveness analysis of TKI for CML found that, when considering the pending loss of patent exclusivity of IM, using IM as a first-line treatment is the most cost-effective treatment option. However, since the loss of patent exclusivity, no studies have considered the cost-effectiveness of IM since the loss of patent exclusivity, nor has the cost-effectiveness of IM TDM been evaluated.

OBJECTIVE: The objective of the study was to determine the cost-effectiveness of using generic IM TDM for the first-line treatment of CML.

METHODS: A peer-reviewed and published TKI cost-effectiveness model in the CML (Padula, WV, et al. JNCI, 2016 Mar 4;108(7)) was modified to include IM TDM as a treatment option. Efficacy inputs for major molecular response (MMR) rates were taken from published clinical studies: IM TDM 65%, dasatinib 52%, nilotinib 53% (Kantarjian H, , et al N Engl J Med. 2010;362:2260-2270; Kantarjian HM, et al. Blood. 2012;119:1123-1129. Larson RA, et al. Leukemia. 2012;26:2197-2203).

Using the Federal Supply Schedule and average and lowest wholesale acquisition cost as price bases, alternative estimates were used for drug prices including generic IM. The cost of TDM for IM was added to the IM TDM comparator arm at $228 annually (6 tests at $38 each) over the 5-year time horizon. Other input costs were updated to 2016 U.S. Dollars using the Medical Service index of the Consumer Price Index.

A U.S. payer perspective was used with a 5-year time horizon and a 3.0% discount rate. The model compared first-line IM TDM versus first-line IM alone, first-line dasatinib or nilotinib (D/N) in terms of costs, quality-adjusted life-years (QALYs), and cost-effectiveness. Univariate (one-way) and multivariate (two-way) sensitivity analysis was performed on all key clinical and economic parameters.

RESULTS:

The model found that IM TDM dominates IM alone with $15,452 to $36,940 in savings and 0.25 higher QALYs. Using an FSS price basis, per patient total costs for IM and IM TDM were $270,905 and $233,965, respectively. For WAC average pricing, these costs were $461,657 and $446,205, respectively, and for the lowest WAC pricing, these costs were $366,966 and $350,090, respectively.

The results comparing first line using of IM TDM to D/N found that IM TDM had slightly higher QALYs and lower costs (0.08 QALYs, and $117,006 to $172,420 savings per patient [varying by price basis]). Thus, in terms of cost-effectiveness, IM TDM dominates D/N with both lower costs and higher QALYs.

The model also found that for each first-line IM TDM patient responding for 5 years $114,577 to $207,564 was saved versus patients receiving first-line D/N. Sensitivity analysis confirmed that the results are robust.

CONCLUSION:

The analysis found that IM TDM dominates IM alone and D/N under a wide range of price scenarios. The analysis suggests that IM TDM is both a clinically and economically viable first-line treatment option for CML.