Cost-effectiveness of lenalidomide plus rituximab versus rituximab monotherapy in patients with previously treated follicular lymphoma: a societal view

Figures & data

Figure 1. Schematic representation of the de novo model

Table 1. Overview of model input parameters

Type	Parameter	Base case value	SE	Distribution	Lower bound	Upper bound	Source	Remark
Model setting	% discount rate: costs	4.0	NA	NA	NA	NA	Dutch EE guideline [35]	None
	% discount rate: effects	1.5	NA	NA	NA	NA	Dutch EE guideline [35]	None
Patient characteristics	Age, years (mean)	61.18	0.65	Normal	59.89	62.45	AUGMENT study [10]	None
	BSA (mean)	1.85	0.01	Normal	1.82	1.88	AUGMENT study IPD [10]	None
	% female patients	52	NA	Beta	46	58	AUGMENT study IPD [10]	None
Resource use	AE %: neutropenia in R-LEN	0.5	NA	Beta	0.42	0.58	AUGEMENT study IPD [10]	Lower and upper bounds were based on the lower and upper bound probabilities of 2.5% and 97.5%, respectively (based on assumed distribution).
	AE %: leukopenia in R-LEN	0.07	NA	Beta	0.03	0.11	AUGEMENT study IPD [10]	Lower and upper bounds were based on the lower and upper bound probabilities of 2.5% and 97.5%, respectively (based on assumed distribution).
	AE %: anemia in R-LEN	0.05	NA	Beta	0.02	0.09	AUGEMENT study IPD [10]	Lower and upper bounds were based on the lower and upper bound probabilities of 2.5% and 97.5%, respectively (based on assumed distribution).
	AE %: neutropenia in R-mono	0.12	NA	Beta	0.07	0.18	AUGEMENT study IPD [10]	Lower and upper bounds were based on the lower and upper bound probabilities of 2.5% and 97.5%, respectively (based on assumed distribution).
	AE %: leukopenia in R-mono	0.02	NA	Beta	0	0.05	AUGEMENT study IPD [10]	Lower and upper bounds were based on the lower and upper bound probabilities of 2.5% and 97.5%, respectively (based on assumed distribution).
	AE %: anemia in R-mono	0.01	NA	Beta	0	0.02	AUGEMENT study IPD [10]	Lower and upper bounds were based on the lower and upper bound probabilities of 2.5% and 97.5%, respectively (based on assumed distribution).
	Informal care: probability of receiving (in %)	22	5	Gamma	0	60	iMTA iCARE tool based on HRQoL data in AUGMENT	Upper bound probability was based on Doorduijn et al. (2004) [36]
	Informal care time when receiving (hours per week)	16.00	0.81	Gamma	15.11	18.28	iMTA iCARE tool based on HRQoL data in AUGMENT	None
	Patients returning back to work after first-line therapy (in %)	50	5	Beta	40	60	Arboe et al [37].	None
Prices	Drug acquisition: lenalidomide 2.5 mg	226.21	NA	NA	NA	NA	G-standaard via Z-index	A 10% and 20% discount for the price of lenalidomide was considered in scenario analyses
	Drug acquisition: lenalidomide 5 mg	232.54	NA	NA	NA	NA	G-standaard via Z-index	A 10% and 20% discount for the price of lenalidomide was considered in scenario analyses
	Drug acquisition: lenalidomide 7.5 mg	238.87	NA	NA	NA	NA	G-standaard via Z-index	A 10% and 20% discount for the price of lenalidomide was considered in scenario analyses
	Drug acquisition: lenalidomide 10 mg	241.16	NA	NA	NA	NA	G-standaard via Z-index	A 10% and 20% discount for the price of lenalidomide was considered in scenario analyses
	Drug acquisition: lenalidomide 15 mg	248.99	NA	NA	NA	NA	G-standaard via Z-index	A 10% and 20% discount for the price of lenalidomide was considered in scenario analyses
	Drug acquisition: lenalidomide 20 mg	259.18	NA	NA	NA	NA	G-standaard via Z-index	A 10% and 20% discount for the price of lenalidomide was considered in scenario analyses
	Drug acquisition: lenalidomide 25 mg	265.12	NA	NA	NA	NA	G-standaard via Z-index	A 10% and 20% discount for the price of lenalidomide was considered in scenario analyses
	Drug acquisition: rituximab 100 mg (i.v.)	227.46	NA	NA	NA	NA	G-standaard via Z-index	None
	Drug acquisition: rituximab 500 mg (i.v.)	1,137.32	NA	NA	NA	NA	G-standaard via Z-index	None
	Drug acquisition: rituximab 1400 mg (s.c.)	1,680.71	NA	NA	NA	NA	G-standaard via Z-index	None
	Physician specialist (per consultation)	120.64	12.06	Gamma	98.16	145.41	Dutch EE guideline [35]	None
	Follow-up price: CT	188.3	18.83	Gamma	153.21	226.96	Dutch EE guideline [35]	None
	Follow-up price: Outpatient clinic	140.92	14.09	Gamma	114.66	169.85	Dutch EE guideline [35]	None
	Imaging price: abdominal ultrasound	120.9	12.09	Gamma	98.37	145.72	Dutch EE guideline [35]	None
	Lab price: TSH	4.77	0.48	Gamma	3.88	5.75	Dutch EE guideline [35]	None
	Lab price: LDH	1.81	0.18	Gamma	1.47	2.18	Dutch EE guideline [35]	None
	Lab price: WBC	1.80	0.18	Gamma	1.46	2.17	Dutch EE guideline [35]	None
	Lab price: platelets	1.78	0.18	Gamma	1.45	2.15	Dutch EE guideline [35]	None
	Lab price: hemoglobin	1.73	0.17	Gamma	1.41	2.09	Dutch EE guideline [35]	None
	Lab price: creatinine	1.64	0.16	Gamma	1.33	1.98	Dutch EE guideline [35]	None
	Informal care price (per hour)	14.95	1.5	Gamma	12.16	18.02	Dutch EE guideline [35]	None
	Productivity loss price (per hour)	37.08	3.71	Gamma	30.17	44.69	Dutch EE guideline [35]	None
Costs	Drug administration: i.v. therapy	167.82	12.6	Gamma	144.03	193.41	Franken et al [28].	None
	Drug administration: s.c. therapy	56.54	5.87	Gamma	45.63	68.6	Franken et al [28].	None
	Travel costs: for i.v. administration	33.39	3.34	Gamma	27.17	40.24	Franken et al [28].	None
	Travel costs: for s.c. administration	8.2	0.82	Gamma	6.67	9.88	Franken et al [28].	None
	AE costs: neutropenia	1171.24	530.82	Gamma	373.01	2417.96	Bouwmans et al [29].	None
	AE costs: leukopenia	1171.24	530.82	Gamma	373.01	2417.96	Bouwmans et al [29].	None
	AE costs: anemia	1595.38	479.52	Gamma	798.45	2663.5	Bouwmans et al [29].	None
Utilities and disutilities	Utility: PFS	0.854	0.01	Beta	0.754	0.954	AUGEMENT study IPD [10]	None
	Utility: PD	0.854	0.01	Beta	0.754	0.954	AUGEMENT study IPD [10]	None
	Disutility: neutropenia	0.090	0.02	Beta	0.059	0.120	Nafees et al [30].	None
	Disutility: leukopenia	0.090	0.02	Beta	0.059	0.120	Assumed to be the same as neutropenia	None
	Disutility: anemia	0.119	0.02	Beta	0.073	0.165	Swinburn et al [31].	None

AE = adverse event; BSA = Body surface area; CT = computerized tomography scan; EE = economic evaluation; HRQoL = health-related quality of life; IPD = individual patient data; i.v. = intravenous; LDH = lactate dehydrogenase; mg = milligram; NA = not applicable; PD = progressive disease; PFS = progression free survival; R-LEN = rituximab plus lenalidomide; R-mono = rituximab monotherapy; s.c. = subcutaneous; SE = standard error; TSH = thyroid stimulating hormone; WBC = white blood cells;

Figure 2. Empirical and extrapolated PFS

PFS = progression-free survival; R-LEN = rituximab plus lenalidomide; R-mono = rituximab monotherapy

Figure 3. Empirical and extrapolated OS

OS = overall survival; R-LEN = rituximab plus lenalidomide; R-mono = rituximab monotherapy

Table 2. Model results: costs, effects, and increments

		Costs in EUR										Effects
Perspective		Drug acquisition	Drug administration	Adverse events	Subsequent treatment	Follow-up	Informal care	Productivity losses	Future medical (unrelateddiseases)	Future non-medical	Total costs	Life years(PFS; PD)	QALYs (PFS; PD)
Societal	R-LEN	57,455	1,096	743	19,990	8,692	28,128	6,123	78,127	NA	200,355	12.9 (3.2; 0)	10.8 (2.8; 8)
	R-mono	6,972	692	176	21,240	7,677	23,952	6,119	65,960	NA	132,789	10.9 (1.7; 9.1)	9.1 (1.5; 7.6)
	Increments	50,483	404	567	−1,250	1,015	4,176	4	12,167	NA	67,566	2 (1.5; 0.5)	1.7 (1.3; 0.4)
Healthcare	R-LEN	57,455	957	743	19,805	8,459	NA	NA	78,127	NA	165,547	12.9 (3.2; 0)	10.8 (2.8; 8)
	R-mono	6,972	592	176	21,043	7,479	NA	NA	65,960	NA	102,223	10.9 (1.7; 9.1)	9.1 (1.5; 7.6)
	Increments	50,483	365	567	−1,238	980	NA	NA	12,167	NA	63,324	2 (1.5; 0.5)	1.7 (1.3; 0.4)
Societal incl. futurenon-medical consumption costs	R-LEN	57,455	1,096	743	19,990	8,692	28,128	6,123	78,127	99,588	299,943	12.9 (3.2; 0)	10.8 (2.8; 8)
	R-mono	6,972	692	176	21,240	7,677	23,952	6,119	65,960	84,899	217,687	10.9 (1.7; 9.1)	9.1 (1.5; 7.6)
	Increments	50,483	404	567	−1,250	1,015	4,176	4	12,167	14,689	82,256	2 (1.5; 0.5)	1.7 (1.3; 0.4)

EUR = Euro (currency); PD = progressive disease; PFS = progression free survival; QALYs = quality-adjusted life years; R-LEN = rituximab plus lenalidomide; R-mono = rituximab monotherapy

Table 3. Incremental cost-effectiveness ratios

	Perspective
	Societal	Healthcare	Societal incl. future non-medical consumption costs
Incremental costs (EUR) per LY gained	33,681	31,567	41,004
Incremental costs (EUR) per QALY gained	40,493	37,951	49,296

EUR = Euro (currency); LY = life years; QALY = quality-adjusted life year.

Figure 4. Tornado diagram (societal perspective

AE = adverse event; PD = progressive disease; PF = progression-free; R-LEN = rituximab plus lenalidomide

Figure 5. Cost-effectiveness plane (societal perspective)

EUR = Euro (currency); QALYs = quality-adjusted life years; WTP = willingness-to-pay

Figure 6. Cost-effectiveness acceptability curve (societal perspective)

WTP = willingness-to-pay; R-LEN = rituximab plus lenalidomide; R-mono = rituximab monotherapy

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