Introduction

Decitabine (Dec) is not approved in the United States (US) for acute myeloid leukemia (AML) because it did not improve overall survival compared with standard conventional induction treatment. We asked what would be the cost effectiveness of Dec versus conventional induction therapy in AML patients (pts) older than 60 years of age.

Methods

The standard conventional induction including cytarabine, and daunorubicin, (AD) (N Engl J Med. 2009 361:1235-48) was compared with Dec (Haematologica. 2012 97:393-401) using a semi-Markov model compiling survival and cost data. Survival probabilities were retrieved from the literature. Data accounted for re-induction therapy with IDA-FLAG (idarubicin, fludarabine, cytarabine and granulocyte colony-stimulating factor) and consolidation therapy with high-dose cytarabine (HiDAC) but not for stem cell transplantation. The assumption-based model considered a maximum of 4 cycles of HiDAC and continuing Dec until loss of benefit. Drug costs were derived from the 2012 US market. Hospital costs accrued were evaluated in a diagnosis-related group (DRG) system. Drug dosage was estimated based on a body surface area of 1.85 m2. The quality of life (QoL) was assumed as 1 for healthy individuals; 0 for death; 0.524 for active disease; 0.91 for AML in remission on AD; 0.71 and 0.524 for AML being actively treated with Dec or AD, and 0.81 for AML in remission treated with Dec or HIDAC. QoL data were based on the literature except for pts on consolidation therapy. The latter was the mean of QoL of AML in remission and AML actively being treated.

Results

Assuming 1,000 pts for each treatment arm in a semi-Markov model over 1 year time horizon, the quality-adjusted life year (QALY) for AD vs. Dec was 0.1754 and 0.5982. The percentage survival for AD and Dec was 45.2% and 50.5%. Their costs were $127,867 and $55,777. The incremental cost-effectiveness ratio (ICER) was -$72,090/0.4228 = -$170,506/year. By sensitivity analysis, Dec was superior to AD to all parameters (Table 1).

Table 1

Ranges for parameters and effect on ICER for one-way sensitivity analysis.

Parameter[1]ICER (per QALY gained)
UpperLower
Total cost of AD (± 10%) -909,752 -541,378 
Total cost of Dec (± 10%) -613,934 -837,196 
Discount rate (10% and 0%) -749,138 -701,802 
QoL for AD (± 10%) -1,194,505 -521,022 
QoL for Dec (± 10%) -460,870 -1,704,558 
Time Horizon (± 3 months) -757,490 -716,384 
Time Horizon (± 6 months) -800,484 -766,769 
HR/OS rate [2] -676,830 -752,498 
HR/OS adjustment done on AD only -465,878 -1,056,103 
HR/OS adjustment done on Dec only -1,187,486 -547,913 
Parameter[1]ICER (per QALY gained)
UpperLower
Total cost of AD (± 10%) -909,752 -541,378 
Total cost of Dec (± 10%) -613,934 -837,196 
Discount rate (10% and 0%) -749,138 -701,802 
QoL for AD (± 10%) -1,194,505 -521,022 
QoL for Dec (± 10%) -460,870 -1,704,558 
Time Horizon (± 3 months) -757,490 -716,384 
Time Horizon (± 6 months) -800,484 -766,769 
HR/OS rate [2] -676,830 -752,498 
HR/OS adjustment done on AD only -465,878 -1,056,103 
HR/OS adjustment done on Dec only -1,187,486 -547,913 

1.Variation of parameter by 10% range was based on prior published report.

2.Variation for HR/OS (hazard ratio for overall survival) was based on HR 0.5 +/- 0.05. .

Conclusion

Dec is a more cost-effective therapy for pts older than 60 years of age than conventional induction therapy. Given the economic pressures in the US Health System, one should consider approving Dec for newly diagnosed AML pts older than 60 years of age.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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