Costs and clinical variables included in the model
| Model variable . | Oral azacitidine . | Observation . | Reference . | ||
|---|---|---|---|---|---|
| Base-case scenario . | Range . | Base-case scenario . | Range . | ||
| Clinical variables | |||||
| Rate of dose escalation to 21-day course | 0.21 | 0.105-0.315 | NA | NA | 2 |
| Median number of cycles with escalated dose | 2 | 1-3 | NA | NA | 2 |
| Median duration of treatment | 11.4 mo | NA | 6.1 mo | NA | 2 |
| Salvage therapies used Intensive chemotherapy Allogeneic HCT Lower-intensity therapy FLT3 inhibitor* IDH1/2 inhibitor* Other lower-intensity therapy Best supportive care only | 0.290 0.060 0.4 0.112 (= 0.4 × 0.28) 0.080 (= 0.4 × 0.20) 0.208 0.420 | 0.145-0.435 0.030-0.090 0.056-0.168 0.040-0.120 0.104-0.312 0.210-0.630 | 0.380 0.140 0.47 0.132 (= 0.4 × 0.28) 0.094 (= 0.4 × 0.20) 0.244 0.270 | 0.190-0.570 0.070-0.210 0.066-0.198 0.047-0.141 0.122-0.366 0.135-0.405 | 2 2 2 2 2 2 2 |
| Monthly treatment discontinuation rate because of adverse events | 0.012 | 0.006-0.018 | NA | NA | 2 |
| Cumulative probability of dose interruption rate due to adverse events | 0.43 | 0.215-0.645 | NA | NA | 2 |
| Duration of dose interruption | 7 d | 4-10 d | NA | NA | Expert opinion |
| Treatment costs | |||||
| Average wholesale price of oral azacitidine (monthly) | $25 389.73 | NA | NA | NA | 15 |
| Discount for average sales price of oral azacitidine | 0.28 | 0.18-0.38 | NA | NA | 16,17 |
| Cost of various salvage regimens Intensive chemotherapy Allogeneic HCT FLT3 inhibitor (gilteritinib) IDH1/2 inhibitor (ivosidenib/enasidenib) Other lower-intensity therapy Best supportive care only (monthly) | $153 737.26 $145 891.52 $26 037.62/cycle $29 782.20/cycle $10 521.87/cycle $5094.56 | $76 869-$230 606 $72 946-$218 837 NA NA $5261-$15 783 $2548-$7643 | $153 737.26 $145 891.52 $26 037.62 $29 782.20 $10 521.87 $5094.56 | $76 869-$230 606 $72 946-$218 837 NA NA $5261-$15 783 $2548-$7643 | 10 9 27 28 8 13 |
| Number of FLT3 inhibitor salvage therapy cycles | 5 | 3-8 cycles | 5 | 3-8 cycles | 27 |
| Number of IDH inhibitor salvage therapy cycles | 5 | 3-8 cycles | 5 | 3-8 cycles | 28 |
| Number of other lower-intensity salvage therapy cycles | 6 | 3-9 cycles | 6 | 3-9 cycles | 8 |
| Cost of office visit (monthly) | $682.57 | $342-$1025 | $682.57 | $342-$1025 | 12 |
| Cost of AML-related hospitalization (per month) | $4840.08 | $2420-$7260 | $6921.5 | $2420-$7260 | 7 |
| Cost of terminal care | $188 677.66 | $94 339-$283 017 | $188 677.66 | $94 339-$283 017 | 11 |
| Utility | |||||
| Utility of active/relapsed AML | 0.53 | 0.48-0.58 | 0.53 | 0.48-0.58 | 21 |
| Utility of AML in early remission (<7 mo) | 0.66 | 0.60-0.72 | 0.66 | 0.60-0.72 | 19 |
| Utility of AML in prolonged remission (≥7 mo) | 0.82 | 0.74-0.90 | 0.82 | 0.74-0.90 | 20 |
| Model variable . | Oral azacitidine . | Observation . | Reference . | ||
|---|---|---|---|---|---|
| Base-case scenario . | Range . | Base-case scenario . | Range . | ||
| Clinical variables | |||||
| Rate of dose escalation to 21-day course | 0.21 | 0.105-0.315 | NA | NA | 2 |
| Median number of cycles with escalated dose | 2 | 1-3 | NA | NA | 2 |
| Median duration of treatment | 11.4 mo | NA | 6.1 mo | NA | 2 |
| Salvage therapies used Intensive chemotherapy Allogeneic HCT Lower-intensity therapy FLT3 inhibitor* IDH1/2 inhibitor* Other lower-intensity therapy Best supportive care only | 0.290 0.060 0.4 0.112 (= 0.4 × 0.28) 0.080 (= 0.4 × 0.20) 0.208 0.420 | 0.145-0.435 0.030-0.090 0.056-0.168 0.040-0.120 0.104-0.312 0.210-0.630 | 0.380 0.140 0.47 0.132 (= 0.4 × 0.28) 0.094 (= 0.4 × 0.20) 0.244 0.270 | 0.190-0.570 0.070-0.210 0.066-0.198 0.047-0.141 0.122-0.366 0.135-0.405 | 2 2 2 2 2 2 2 |
| Monthly treatment discontinuation rate because of adverse events | 0.012 | 0.006-0.018 | NA | NA | 2 |
| Cumulative probability of dose interruption rate due to adverse events | 0.43 | 0.215-0.645 | NA | NA | 2 |
| Duration of dose interruption | 7 d | 4-10 d | NA | NA | Expert opinion |
| Treatment costs | |||||
| Average wholesale price of oral azacitidine (monthly) | $25 389.73 | NA | NA | NA | 15 |
| Discount for average sales price of oral azacitidine | 0.28 | 0.18-0.38 | NA | NA | 16,17 |
| Cost of various salvage regimens Intensive chemotherapy Allogeneic HCT FLT3 inhibitor (gilteritinib) IDH1/2 inhibitor (ivosidenib/enasidenib) Other lower-intensity therapy Best supportive care only (monthly) | $153 737.26 $145 891.52 $26 037.62/cycle $29 782.20/cycle $10 521.87/cycle $5094.56 | $76 869-$230 606 $72 946-$218 837 NA NA $5261-$15 783 $2548-$7643 | $153 737.26 $145 891.52 $26 037.62 $29 782.20 $10 521.87 $5094.56 | $76 869-$230 606 $72 946-$218 837 NA NA $5261-$15 783 $2548-$7643 | 10 9 27 28 8 13 |
| Number of FLT3 inhibitor salvage therapy cycles | 5 | 3-8 cycles | 5 | 3-8 cycles | 27 |
| Number of IDH inhibitor salvage therapy cycles | 5 | 3-8 cycles | 5 | 3-8 cycles | 28 |
| Number of other lower-intensity salvage therapy cycles | 6 | 3-9 cycles | 6 | 3-9 cycles | 8 |
| Cost of office visit (monthly) | $682.57 | $342-$1025 | $682.57 | $342-$1025 | 12 |
| Cost of AML-related hospitalization (per month) | $4840.08 | $2420-$7260 | $6921.5 | $2420-$7260 | 7 |
| Cost of terminal care | $188 677.66 | $94 339-$283 017 | $188 677.66 | $94 339-$283 017 | 11 |
| Utility | |||||
| Utility of active/relapsed AML | 0.53 | 0.48-0.58 | 0.53 | 0.48-0.58 | 21 |
| Utility of AML in early remission (<7 mo) | 0.66 | 0.60-0.72 | 0.66 | 0.60-0.72 | 19 |
| Utility of AML in prolonged remission (≥7 mo) | 0.82 | 0.74-0.90 | 0.82 | 0.74-0.90 | 20 |
Model assumptions were derived preferentially from the QUAZAR AML-001 trial and its post hoc analyses.2,29 If not available, costs and utilities were derived from the literature reporting cost and treatment patterns from a US perspective. If data from both a Medicare and commercial insurance perspective were available, Medicare data were used given the primarily older population in the QUAZAR AML-001 study. All costs were adjusted for inflation to 2020 USD. Costs and utilities were varied by 50% and 10%, respectively, during sensitivity analyses.
Among patients treated with lower-intensity therapies, we assumed that patients with targetable mutations in FLT3, IDH1, or IDH2 would be treated with gilteritinib, ivosidenib, or enasidenib, respectively. As the percentage of patients with these mutations was not specified in the QUAZAR AML-001 study, we assumed a prevalence of those mutations similar to AML patients included in the Cancer Genome Analysis.30 The duration of treatment with subsequent lower-intensity therapies was derived from the literature for the respective agents.8,27,28