Cost-effectiveness of pembrolizumab versus brentuximab vedotin for patients with relapsed or refractory classical Hodgkin’s lymphoma: a United States payer perspective

Figures & data

Figure 1. Transition state Markov model. All patients with RRcHL enter the model in the progression-free state. Patients are initiated on pembrolizumab or BV. In each model cycle, patients can remain progression-free, transition to progressed disease, or die. Patients with progressed disease can only transition to the death state.

Figure 2. Progression-free survival parametric extrapolations. KM, Kaplan-Meier.

Figure 3. Deterministic sensitivity analysis results. (a) Incremental costs of pembrolizumab vs BV; (b) Incremental QALYs of pembrolizumab vs BV.

Table 1. Summary of model inputs.

Treatment	Dose regimen	Acquisition		Administration cost per treatment cycle ($)
		WAC ($)	Cost per treatment cycle ($)
Pembrolizumab	200 mg every 3 weeks, max. 35 cycles^26	4,513.20/100 mg vial	9,026.40	279.30
BV	1.8 mg/kg every 3 weeks, max. 16 cycles^21	6,832.00/50 mg vial	22,144.72	279.30
Subsequent therapy
GVD	GEM: 800 mg/m^2 VIN: 15 mg/m^2 DOX: 10 mg/m^22 per 3 weeks^40^,^41	GEM: 15.31/200 mg; 59.19/1000 mg; 106.24/2000 mg VIN: 18.00/10 mg; 90.00/50 mg DOX: 959.30/20 mg; 2,398.30/50 mg	1,650.39	611.80
GV	GEM: 1000 mg/m^2 VIN: 25mg/m^22 per 3 weeks^41	GEM: 15.31/200mg; 59.19/1000 mg; 106.24/2000 mg VIN: 18.00/10 mg; 90.00/50 mg
Bendamustine	120 mg/m^2 2 per 4 weeks, max 6 cycles^42	726.60/25 mg 2,906.40/100 mg	13,979.78	558.60
Gemcitabine	1000 mg/m^2 3 per 4 weeks^43	15.31/200 mg 59.19/1000 mg 106.24/2000 mg	341.90	837.90

Table

Disease management^36	Cost per week ($)
	Outpatient	Inpatient
PF health state	351.87	0.00
PD health state	607.15	151.79

Table

Adverse events (grade ≥3)	Incidence (%)		Unit cost per event ($)
	Pembrolizumab	BV
Neutropenia	0	19.6	11,857.05
Peripheral sensory neuropathy	0	7.8	11,198.27
Thrombocytopenia	1.7	7.8	9,790.27
Anemia	0	5.9	6,969.12
Source	KEYNOTE-087 (Cohort 3)^26	SG035-0003^27	HCUP^37

Abbreviations. BV, brentuximab vedotin; DOX, pegylated liposomal doxorubicin; GEM, gemcitabine; GV, Gemcitabine and vinorelbine; GVD, gemcitabine, vinorelbine, and pegylated liposomal doxorubicin; HCUP, Healthcare Cost and Utilization Project; PD, progressed disease; PF, progression-free; VIN, vinorelbine; WAC, wholesale acquisition cost.

Table 2. Summary of model utility inputs.

Health states	Utility, mean (SE)	References
PF (all treatments)	0.821 (0.006)	Merck^26
PD (all treatments)	0.380 (0.028)	Swinburn et al.^35

Table

Adverse events	Utility decrement	References	Mean duration, days	References	Adverse Event utility decrement^a
Neutropenia	–0.090, –0.163	Nafees et al.^44; Tolley et al.^45	(9.547 + 9.291)/2 = 9.42^b, 15.1	NICE^46^,^47	–0.004
Peripheral sensory neuropathy	–0.19	Best et al.^48	(26.917 + 28.000)/2 = 27.4	NICE^46	–0.014
Thrombocytopenia	–0.108	Tolley et al.^45	23.2	NICE^47	–0.007
Anemia	–0.09, –0.09	Beusterien et al.^49	(12.4 + 14.5)/2 = 13.45^a, 16.1	NICE^46^,^47	–0.004

Abbreviations. PD, progressed disease; PF, progression-free.

^a Where two mean durations are presented, the adverse event utility decrement is the average of the utility decrement multiplied by the mean duration.

^b The average of both arms from within an individual citation was used.

Table 3. Scenario analysis of incremental costs and QALYs for pembrolizumab vs BV.

Scenario	Base case setting	Incremental QALYs	Incremental cost ($)	Incremental cost per QALY, $
Base case	—	0.500	–63,278	Dominant
Time horizon: 10 years	20 Years	0.467	–65,616	Dominant
Time horizon: 30 years	20 Years	0.503	–63,126	Dominant
PFS assessment by investigator report	IRC	0.379	–77,888	Dominant
Treatment acquisition costs based on ToT curve	PFS	0.500	–55,606	Dominant
PFS survival function modeled as generalized gamma distribution	Log-normal distribution	0.925	–47,930	Dominant
PD health state utility for pembrolizumab from KEYNOTE-087	Based on literature^35	0.475	–63,278	Dominant
Vial sharing (no BV wastage)	Optimal wastage algorithm (BV wastage)	0.500	–24,857	Dominant
Exclusion of all subsequent treatments	Subsequent treatments included	0.500	–63,033	Dominant
Assume no treatment effect beyond 24 months	Treatment effect through the end of the time horizon	0.352	–65,914	Dominant
Including relative dose intensity	Excluded	0.500	–51,498	Dominant

Abbreviations. BV, brentuximab vedotin; IRC, Independent review committee; PD, Progressed disease; PFS, Progression-free survival; QALY, quality-adjusted life-year; ToT, Time on treatment.

Table 4. Costs and outcomes for treatment with pembrolizumab or BV.

Parameter	Pembrolizumab	BV	Incremental, pembrolizumab vs BV
Costs, $
PF	27,533	15,907	11,626
PD	106,814	109,148	–2,333
Drug acquisition	178,285	248,727	–70,441
Drug administration	5,470	3,137	2,333
Subsequent treatment	12,772	13,017	–244
Adverse events	163	4,381	–4,218
Total	331,038	394,316	–63,278
QALYs
PF	1.231	0.711	0.520
PD	1.025	1.047	–0.022
Adverse events	0.000	–0.003	0.003
Total	2.256	1.756	0.500
Lys
Total LYs	4.197	3.623	0.574
ICERs
Incremental cost, $/LY	—	—	(dominant)
Incremental cost, $/QALY	—	—	(dominant)

Abbreviations. BV, brentuximab vedotin; ICER, incremental cost-effectiveness ratio; LY, life-year; PD, progressed disease; PF, progression-free; QALY, quality-adjusted life-year.

Figure 4. Probabilistic sensitivity analysis (10,000 iterations). (a) Cost-effectiveness plane of pembrolizumab vs BV; (b) Cost-effectiveness acceptability curve of pembrolizumab vs BV.

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