Cost-effectiveness analysis of rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China

Figures & data

Figure 1. Decision tree models: (a) TLS prevention and (b) TLS treatment. Abbreviations. SOC, standard of care; HF, hemofiltration; TLS, Tumor lysis syndrome.

Figure 2. Tornado diagrams: One-way sensitivity analysis of ICER per QALY gained comparing rasburicase vs SOC for patients with AML during (a) TLS prevention and (b) TLS treatment. Abbreviations. SOC, Standard of Care; TLS, tumor lysis syndrome; AML, acute myeloid leukemia; QALY, quality-adjusted life year; ICER, incremental cost-effectiveness ratios.

Table 1. Failure rates of TLS during prevention and treatment for different hematologic malignancies.

Treatment options	Failure rate of TLS prevention or treatment
	AML	ALL	NHL
Prevention period
Rasburicase^3	4.2%	7.5%	7.2%
SOC^8	5.4%	9.7%	9.4%
Treatment period
Rasburicase^9	8.0%	8.0%	8.0%
HF^8	13.9%	14.9%	15.7%

Abbreviations. ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; HF, hemofiltration; NHL, non-Hodgkin’s lymphoma; SOC, standard of care.

Table 2. Incidence rate of HF-induced AEs.

HF-induced AEs	Incidence rate
% patients experience acute AEs requiring medical intervention	4.4
% patients experiences kidney damage	4.2
% patients with HF related kidney damage requiring long-term treatment	10.8

Abbreviations: AE, adverse event; HF, hemofiltration.

Table 3. Costs related to SOC for patients with AML, ALL, and NHL during both prevention and treatment periods.

	AML ($)		ALL ($)		NHL ($)
	Prevention	Treatment	Prevention	Treatment	Prevention	Treatment
Hydration	41.49	86.12	40.88	71.77	39.55	82.23
Alkalization	23.78	69.16	22.80	53.68	22.90	61.23
Allopurinol	11.30	29.88	10.98	29.88	11.01	37.29
Furosemide	6.32	22.16	6.09	21.91	6.12	23.71
DU	3.88	43.07	3.50	33.70	3.54	33.70
HF	N/A	1,381.23	N/A	1,640.77	N/A	1,525.22
Laboratory fee	184.42	224.38	184.42	224.38	184.42	267.82
Image	143.54	151.86	143.54	151.10	143.54	152.61
Inpatient administration	170.74	665.37	170.74	604.93	170.74	590.95
Hospitalization bed fee per day	75.59	42.34	75.59	21.94	75.59	22.10
Length of stay (days)	5.10	8.95	5.10	9.45	5.10	10.40

Abbreviations. ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; DU, low molecular dextran; HF, hemofiltration; NHL, non-Hodgkin’s lymphoma; SOC, standard of care.

Table 4. Long-term treatment costs and length of managing underlying diseases using early-phase treatment and consolidation therapy for patients without and with experiencing TLS.

		ALL		AML		NHL
		Patient without TLS	Patient with TLS	Patient without TLS	Patient with TLS	Patient without TLS	Patient with TLS
Early-phase treatment	Duration (years)	8.75	9.3	6.45	6.90	4.80	5.20
	Costs ($)	17,943.12	19,130.58	20,392.32	21,116.22	17,980.9	19,008.38
Consolidation therapy	Duration (years)	18.25	20.8	12.70	13.90	11.32	12.20
	Costs ($)	16,847.65	18,675.96	14,033.41	15,110.00	13,479.78	14,250.24

Abbreviations. ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; NHL,non-Hodgkin’s lymphoma; TLS, Tumor lysis syndrome.

Table 5. Treatment information for HF-induced AEs.

Description	Value
HF induced acute AE total treatment cost (per episode)	$1,376.68
HF induced kidney damage total treatment cost (per episode)	$10,939.64
HF induced kidney damage treatment duration (per episode)	2.6 years

Abbreviations. AE, adverse event; HF, hemofiltration.

Table 6. Median life expectancy (years) for pediatric patients without TLS history and with cured TLS.

	AML	ALL	NHL
Patient without TLS history	27.6	47.1	49.3
Patient with cured TLS	27.6	47.1	49.3

Abbreviations. ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; NHL, non-Hodgkin’s lymphoma; TLS, Tumor lysis syndrome.

Table 7. Sensitivity analysis parameters.

Parameters	One-way sensitivity analysis		PSA
	Base case value	Range	Standard error	Distribution
AMl
Rasburicase preventive failure rate (%)	4.2	3.4–5.0	1.22	Beta
SOC preventive failure rate (%)	5.4	4.4–6.5	2.86	Beta
Rasburicase treatment failure rate (%)	8.0	6.4–9.6	1.83	Beta
HF treatment failure rate (%)	13.9	11.1–16.7	3.41	Beta
Patients with KD (%)	4.2	3.4–5.0	2.10	Beta
KD patients who need long-term treatment (%)	10.8	8.6–13.0	5.40	Beta
Patient life expectancy without TLS (years)	27.60	22.08–33.12	2.76	Gamma
Patient life expectancy with TLS cured (years)	27.60	22.08–33.12	2.76	Gamma
Cost per vial of rasburicase ($)	250.83	200.66–300.99	23.35	Gamma
ALL
Rasburicase preventive failure rate (%)	7.5	6.0–9.0	1.22	Beta
SOC preventive failure rate (%)	9.7	7.8–11.6	2.86	Beta
Rasburicase treatment failure rate (%)	8.0	6.4–9.6	1.83	Beta
HF treatment failure rate (%)	14.9	11.9–17.8	3.41	Beta
Patients with KD (%)	4.2	3.4–5.0	2.10	Beta
KD patients who need long-term treatment (%)	10.8	8.6–13.0	5.40	Beta
Patient life expectancy without TLS (years)	47.10	37.68–56.52	4.71	Gamma
Patient life expectancy with TLS cured (years)	47.10	37.68–56.52	4.71	Gamma
Cost per vial of rasburicase ($)	250.83	200.66–300.99	23.35	Gamma
NHL
Rasburicase preventive failure rate (%)	7.2	5.8–8.7	1.22	Beta
SOC preventive failure rate (%)	9.4	7.5–11.3	2.86	Beta
Rasburicase treatment failure rate (%)	8.0	6.4–9.6	1.83	Beta
HF treatment failure rate (%)	15.7	12.5–18.8	3.41	Beta
Patients with KD (%)	4.2	3.4–5.0	2.10	Beta
KD patients who need long-term treatment (%)	10.8	8.6–13.0	5.40	Beta
Patient life expectancy without TLS (years)	49.30	39.44–59.16	4.93	Gamma
Patient life expectancy with TLS cured (years)	49.30	39.44–59.16	4.93	Gamma
Cost per vial of rasburicase ($)	250.83	200.66–300.99	23.35	Gamma

Abbreviations. ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; HF, hemofiltration; KD, kidney damage; NHL, non-Hodgkin’s lymphoma; PSA, probabilistic sensitivity analysis; SOC, standard of care; TLS, tumor lysis syndrome.

Table 8. Treatment outcomes, costs, and ICER per QALY gained for rasburicase and SOC during TLS prevention.

	AML		ALL		NHL
	Rasburicase	SOC	Rasburicase	SOC	Rasburicase	SOC
Total cost ($)	38,171.75	35,523.20	37,722.78	34,893.88	34,745.18	31,926.65
Total QALY	21.21	21.06	36.19	35.70	37.88	37.35
ICER ($/QALY)	17,580.04	—	5,783.45	—	5,391.00	—

Abbreviations. ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; ICER, incremental cost-effectiveness ratios; NHL, non-Hodgkin’s lymphoma; QALY, quality adjust life year; SOC, standard of care; TLS, Tumor lysis syndrome.

Table 9. Treatment outcomes, costs, and ICER per QALY gained for rasburicase and SOC during TLS treatment.

	AML		ALL		NHL
	Rasburicase	SOC	Rasburicase	SOC	Rasburicase	SOC
Total cost ($)	40,365.53	34,851.10	40,277.86	34,620.75	36,202.08	30,794.72
Total QALY	20.99	18.27	35.79	30.84	37.44	31.98
ICER ($/QALY)	2,031.18	—	1,142.93	—	990.37	—

Abbreviations. ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; NHL, non-Hodgkin’s lymphoma; ICER, incremental cost-effectiveness ratios; QALY, quality adjust life year; SOC, standard of care; TLS, Tumor lysis syndrome.

Figure 3. Tornado diagram: One-way sensitivity analysis of ICER per QALY gained comparing rasburicase vs SOC for patients with ALL during (a) TLS prevention and (b) TLS treatment. Abbreviations. SOC, Standard of Care; TLS, tumor lysis syndrome; ALL, acute lymphoid leukemia; QALY, quality-adjusted life year; ICER, incremental cost-effectiveness ratios.

Figure 4. Tornado diagram: One-way sensitivity analysis of ICER per QALY gained comparing rasburicase vs SOC for patients with NHL during (a) TLS prevention and (b) TLS treatment. Abbreviations. SOC, Standard of Care; TLS, tumor lysis syndrome; NHL, non-Hodgkin's lymphoma; QALY, quality-adjusted life year; ICER, incremental cost-effectiveness ratios.

Figure 5. (a). Cost-effectiveness acceptability curve (rasburicase vs SOC) for patients with (a) AML, (b) ALL, and (c) NHL during TLS prevention and TLS treatment. Abbreviations. SOC, Standard of Care; TLS, tumor lysis syndrome; ALL, acute lymphoid leukemia; AML, acute myeloid leukemia; NHL, non-Hodgkin's lymphoma; WTP, willing to pay.

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