The cost-effectiveness of glasdegib in combination with low-dose cytarabine, for the treatment of newly diagnosed acute myeloid leukemia in adult patients who are not eligible to receive intensive induction chemotherapy in Canada

Figures & data

Figure 1. Model structure.

Figure 2. (A) Overall survival curves: main population. (B) Overall survival curves: 20–30% BMB subgroup. (C) Overall survival curves: >30% BMB subgroup. Abbreviations: AZA, azacitidine; BMB, bone marrow blasts; GLAS, glasdegib; KM, Kaplan–Meier; LDAC, low-dose cytarabine.

Figure 3. (A) Derived progression-free-survival curves: main population. (B) Derived progression-free-survival curves: 20–30% BMB subgroup. (C) Derived progression-free-survival curves: >30% BMB subgroup. Abbreviations: AZA, azacitidine; BMB, bone marrow blasts; GLAS, glasdegib; KM, Kaplan–Meier; LDAC, low-dose cytarabine; PFS, progression-free survival.

Table 1. OS HRs of glasdegib + LDAC versus azacitidine obtained from a previous publication¹².

	GLAS + LDAC vs. LDAC	AZA vs. LDAC	GLAS + LDAC vs. AZA
20–30% BMB	0.17 [0.06–0.48]	0.37 [0.12–1.13]	0.46 [0.10, 2.14]
>30% BMB	0.62 [0.38, 1.02]	0.90 [0.70, 1.16]	0.69 [0.39, 1.20]
Remarks	HR in favor of GLAS + LDAC	HR in favor of AZA	HR in favor of GLAS + LDAC

Abbreviations: AZA, azacitidine; BMB, bone marrow blasts; GLAS, glasdegib; HR, hazard ratio; LDAC, low-dose cytarabine; NMA, network meta-analysis; OS, overall survival.

Table 2. Derived remission and non-remission rates.

Response rates – main population	Glasdegib + LDAC (N = 78)	LDAC alone (N = 38)
Remission(%)	38.2%	9.5%
Non-remission(%)	61.8%	90.5%
Response rates – 20–30% BMB group	Glasdegib + LDAC (N = 21)	Azacitidine
Remission(%)	37.5%	8.8%
Non-remission(%)	62.5%	91.2%
Response rates – >30% BMB group	Glasdegib + LDAC (N = 53)	Azacitidine
Remission(%)	41.7%	13.6%
Non-remission(%)	58.3%	86.4%

Abbreviations: AML, acute myeloid leukemia; BMB, blood marrow blasts; IPD, individual patient-level data; LDAC, low-dose cytarabine; NMA, network meta-analysis.

Table 3. Median treatment durations.

Main population	Reported median treatment durations (in months)	Median treatment duration used in the model (in months)
Glasdegib + LDAC	–	2.73
LDAC alone	–	1.33
20–30% BMB population	Reported median treatment durations (in months)	Median treatment duration used in the model (in months)
Glasdegib + LDAC	–	6.18
Azacitidine	8.94	2.68
>30% BMB population	Reported median treatment durations (in months)	Median treatment duration used in the model (in months)
Glasdegib + LDAC	–	2.17
Azacitidine	5.52	2.27

Abbreviations: AML, acute myeloid leukemia; BMB, bone marrow blasts; IPD, individual patient-level data; LDAC, low-dose cytarabine.

Table 4. Health-state utility values.

Health State	Utility value	Source	Notes
Remission	0.9100	Goss et al. 2006^15	Assuming remission state is transfusion independent
Non-remission	0.7100	Batty et al. 2014^16	Assuming it is the same utility as an AML patient treated with decitabine
Relapsed/progressed	0.5000	Goss et al. 2006^15	Assuming it is transfusion dependent state

Abbreviations: AML, acute myeloid leukemia.

Table 5. Costs inputs.

Cost category				Source
Drug cost
Package cost	Glasdegib $17,184.70 (100 mg, 30 tablets)	LDAC $5.09 (100mg, 1 vial)	AZA $599.00 (100mg, 1 vial)	WAC provided by manufacturer. Delta PA. AQPP formulary.
Administration cost
Cost items	Oral drug – $0,00 Chemotherapy session – $1,341.00 Hospital clinic nurse cost (1 hour) – $ 55.07 Homecare nurse cost (1 hour) – $ 55.07 Pharmacist (preparation of the injection, 1 hour) – $ 63.48			Ontario Case Costing. OCC costing analysis tool. Ottawa, ON^18; Ontario Nurses’ Association collective agreement ^19; Ontario Public Service Employees Union^20
Health-state cost
Transfusion (unit cost)	Red blood count transfusion – $262.00 Platelet transfusion – $262.00			Ontario Case Costing^18
Medical resource use (unit cost)	Haematologist – $157.00 (first visit)        $105.25 (subsequent visit) Oncology nurse – $18.36 (assuming each visit takes 20 minutes) Transfusion/outpatient nurse – $18.36 (assuming each visit takes 20 minutes)			OHIP Schedule of Benefits^21 Ontario Nurses’ Association collective agreement^19
Monitoring test (unit cost)	Bone marrow aspirates – $33.90 Bone marrow biopsies – $63.35 Immunophenotyping (flow cytometry) – $150.89 Blood cultures – $14.66 Full blood count – $3.98 Karyotype – $155.10 Biochemistry profile – $3.20			OHIP Schedule of Benefits^21; Ontario Schedule of Benefits for Laboratory Services^22; Manitoba Physician’s Manual^23
End-of-life cost	$ 15,976.00			Yu M et al 2015^24
AE cost (unit cost)	Anemia – $441.00 Neutropenia – $385.00 Febrile neutropenia – $385.00 Thrombocytopenia – $328.00 Pneumonia – $352.00 Platelet count decreased – $328.00			Ontario Case Costing. OCC costing analysis tool. Ottawa, ON. 2017–2018^18

All costs were measured in Canadian dollars.

Abbreviations: AE, adverse event; AZA, azacitidine; LDAC, low-dose cytarabine.

Figure 4. (A) Probabilistic analysis results presented on the cost-effectiveness plane: main population. (B) Probabilistic analysis results presented on the cost-effectiveness plane: 20–30% BMB. (C) Probabilistic analysis results presented on the cost-effectiveness plane: >30% BMB. Abbreviations: BMB, bone marrow blasts; LDAC, low-dose cytarabine; QALY, quality-adjusted life-year.

Figure 5. (A) Cost-effectiveness acceptability curve: main population. (B) Cost-effectiveness acceptability curve: 20–30% BMB. (C) Cost-effectiveness acceptability curve: >30% BMB. Abbreviations: BMB, bone marrow blasts; LDAC, low-dose cytarabine.

Table 6. Probabilistic cost-effectiveness results.

Treatment	Total			Incremental			ICER ($/QALY)
	Costs	LYs	QALYs	Costs	LYs	QALYs
Main population
GLAS + LDAC	$110,632	1.06	0.73
LDAC alone	$37,937	0.50	0.32	$72,695	0.56	0.41	$177,065
20–30% BMB
GLAS + LDAC	$184,807	1.30	0.88
AZA	$124,918	0.85	0.55	$59,889	0.45	0.34	$178,201
>30% BMB
GLAS + LDAC	$93,575	1.03	0.74
AZA	$101,431	0.69	0.46	−$7,856	0.34	0.28	−$28,141 (Dominant)
Weighted average ICER across BMB subgroups GLAS + LDAC vs. AZA							$49,392
Weighted average ICER across all treatments							$81,310

All costs were measured in Canadian dollars.

Abbreviations: AZA, azacitidine; BMB, bone marrow blasts; GLAS, glasdegib; ICER, incremental cost-effectiveness ratio; LDAC, low-dose cytarabine; LY, life-year; QALY, quality-adjusted life-year.

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