Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma post-autologous stem cell transplant: a cost-effectiveness analysis in Scotland

Figures & data

Table 1. Demographic and clinical characteristics of patients enrolled in clinical studies informing the cost-effectiveness model.

	SG035-0003 study^12^,^13^,^15	Robinson et al.^27	Martinez et al.^9^,^28
Cohort (end-points used in the model)	Brentuximab vedotin (PFS, OS); C/R (PFS)	AlloSCT (PFS)	AlloSCT (OS); C/R (OS)
Maximum follow-up, years	PFS = 6.08; OS = 6.08	5.19	AlloSCT = 6.04; C/R = 6.04
Number of patients	102	285	AlloSCT = 133; C/R = 294; 2nd ASCT = 35^*
Median age, years (range)	31 (15–77)	31 (18–57)^†	31 (18–72)^†
Gender, male/female (n)	48/54	163/122	268/194
ECOG PS, n (%)
0	42 (41)	NR	NR
1	60 (59)	NR	NR
Karnofsky status, n (%)
≥80	NR	NR	212 (75)
<80	NR	NR	72 (25)
Prior ASCT, n (%)	102 (100)	— (80)	462 (100)
Median number of prior chemotherapy regimens (range)	3.5 (1–13)	4 (1–8)^‡	NR
Number of therapy lines before ASCT, n (%)
1–2	57 (56)	NR	288 (62)
>2	42 (34)	NR	131 (28)
Median time from ASCT to first post-transplant relapse, months (range)	6.7 (0–131)^§	9	7 (1–78)
Median time from diagnosis to transplantation, months (range)	17.9 (5–115)^§	NR	21 (5–244)
Histologically confirmed CD30-expressing disease, n (%)	102 (100)	NR	NR
Primary refractory to frontline therapy, n (%)	72 (71)	NR	NR
Refractory to most recent therapy, n (%)	43 (42)	NR	— (15)
Baseline B symptoms, n (%)	35 (34)	NR	168 (49)
Bulky disease	NR	NR	— (7)
Stage III at initial diagnosis, n (%)	27 (26)	56 (20)	NR
Stage IV at initial diagnosis, n (%)	20 (20)	72 (25)	NR
Stage III–IV at ASCT failure, n (%)	NR	NR	235 (67)

alloSCT, allogenic stem cell transplant; ASCT, autologous stem cell transplant; C/R, chemotherapy ± radiotherapy; ECOG PS, Eastern Cooperative Oncology Group Performance Status; NR, not reported; OS, overall survival; PFS, progression-free survival.

^* Characteristics include patients who received a second ASCT who were not modeled.

^† Median age at transplant.

^‡ All prior therapies.

^§ Eleven patients (11%) received two prior ASCTs, in these patients, ASCT refers to the most recent ASCT.

Figure 1. Kaplan-Meier estimates of PFS and OS, by comparator. (a) Brentuximab vedotin: PFS (investigator-assessed) and OS were taken from SG035-0003¹², measured from trial entry. (b) C/R: PFS was taken from SG035-0003 for the most recent prior post-ASCT therapy (n = 56), measured from trial entry¹²; OS was taken from Martinez et al., 2013⁹ for C/R, measured from ASCT failure and adjusted for case mix. (c) AlloSCT: PFS was taken from Robinson et al., 2009²⁷ for RIC alloSCT, measured from ASCT failure; OS was taken from Martinez et al., 2013⁹ for RIC and myeloblative alloSCT, measured from ASCT failure and adjusted for case mix. alloSCT, allogenic stem cell transplant; ASCT, autologous stem cell transplant; C/R, chemotherapy ± radiotherapy; PFS, progression-free survival; OS, overall survival; RIC, reduced-intensity conditioning.

Figure 2. Long-term extrapolations of PFS and OS, by comparator. (a) PFS: 0–6.08 years, brentuximab vedotin SG035-0003 data¹² were compared with self-control and Robinson et al., 2009²⁷ data; 6.08 years–lifetime, all comparators were assumed to have the same constant risk of progression. (b) OS: 0–5.67 years, brentuximab vedotin SG035-0003 data¹² were compared directly with Martinez et al., 2013⁹ data; 5.67–6.0 years, brentuximab vedotin data¹² were extrapolated with a hazard ratio of 1.0 applied to the Martinez et al., 2013⁹ hazard; 6.0–lifetime, all comparators were assumed to have the same constant risk of death. alloSCT, allogenic stem cell transplant; C/R, chemotherapy ± radiotherapy; OS, overall survival; PFS, progression-free survival.

Table 2. Discounted life years (LYs), QALYs and costs by resource category.

Comparator	LYs Total	QALYs				Costs
		PFS	PPS	AEs	Total	Acquisition (£)	Admin (£)	Health state (£)	AEs (£)	Total (£)
Brentuximab vedotin	5.43	2.51	0.89	−0.04	3.36	69,335	3,160	15,766	312	88,572
C/R	4.15	0.46	1.35	−0.03	1.79	3,823	3,885	18,551	1,134	27,393
C/R with intent to alloSCT	4.41	1.69	0.90	−0.08	2.51	67,779		17,707	9,507	94,993

AlloSCT, allogenic stem cell transplant; AEs, adverse events; C/R, chemotherapy ± radiotherapy; LYs, life years; PFS, progress-free survival; PPS, post-progression survival; QALYs, quality-adjusted life year.

Table 3. Base case cost-effectiveness.

	Patients eligible for alloSCT		Patients ineligible for alloSCT
Comparator	ICER (£/QALY)	ICER (£/LY)	ICER (£/QALY)	ICER (£/LY)
Brentuximab vedotin	£38,769	£47,593	£38,769	£47,593
C/R	Referent	Referent	Referent	Referent
C/R with intent to  alloSCT	Dominated	Dominated	Not applicable

alloSCT, allogenic stem cell transplant; C/R, chemotherapy ± radiotherapy; ICER, incremental cost-effectiveness ratio; LY, life year; QALY, quality-adjusted life year.

Table 4. Deterministic sensitivity analyses.

Parameters explored	Justification	ICER (£/QALY)
		C/R	C/R with intent to alloSCT	Brentuximab vedotin (£)	Brentuximab vedotin % change vs base case
Base case	For comparison	Referent	Dominated	38,769	0
Named patient program data used for weight distribution	May be more reflective of real world data	Referent	Dominated	39,630	2
8% of patients in brentuximab vedotin arm receive alloSCT	Percentage of patients receiving alloSCT in SG035-0003	Referent	Ext Dominated	45,107	16
18% of patients in brentuximab vedotin arm receive alloSCT	Percentage of first-line post-ASCT patients receiving alloSCT in SG035-0003	Referent	Ext Dominated	53,030	37
30% patients progress to alloSCT	Alternative estimate provided by clinical experts	Referent	Ext Dominated	38,769	0
IRF PFS and response rates for brentuximab vedotin	Alternative PFS assessment from SG035-0003	Referent	Dominated	51,937	34
HR for PFS beyond trial period 1.5 for brentuximab vedotin or C/R vs alloSCT	Explore scenario whereby PFS outcomes during trial are followed by “catch-up” relative to alloSCT	Referent	Dominated	42,966	11
HR for PFS beyond trial period 2.0 for brentuximab vedotin or C/R vs alloSCT	More extreme version of scenario above	Referent	Dominated	45,775	18
Log-normal model used to extrapolate brentuximab vedotin or C/R	Extrapolation based on within trial curve fitting	Referent	Dominated	42,480	10
Maximum follow-up used for OS	Use of full follow-up from SG035-0003	Referent	Dominated	38,073	–2
Weibull used to extrapolate OS	Use of alternative approach to estimating baseline OS	Referent	Dominated	48,671	26
HR for OS beyond trial period 1.5 for brentuximab vedotin vs C/R or alloSCT	Explore scenario whereby OS outcomes during trial are followed by “catch-up” relative to comparators	Referent	Dominated	41,890	8
HR for OS beyond trial period 2.0 for brentuximab vedotin vs C/R or alloSCT	More extreme version of scenario above	Referent	Dominated	42,446	9
Increasing comparator hazards for PFS and OS by 10%	Explore potential bias in relative treatment effects for brentuximab vedotin resulting from naïve comparison	Referent	Dominated	34,800	−10
Decreasing comparator hazards for PFS and OS by 10%	Explore potential bias in relative treatment effects for brentuximab vedotin resulting from naïve comparison	Referent	Dominated	45,457	17
All patients achieve CR utility until progression	Address lack of time-dependency in proportion of CRs in PFS state	Referent	Dominated	34,097	–12
All patients assumed to receive most expensive chemotherapy	Alternative cost scenarios	Referent	Dominated	32,998	–15
All patients assumed to receive least expensive chemotherapy		Referent	Dominated	41,281	6
Post-progression cost increased by 100%		Referent	Dominated	38,279	–1
Post-progression cost set to zero		Referent	Dominated	39,260	1

alloSCT, allogenic stem cell transplant; C/R, chemotherapy ± radiotherapy; CR, complete remission; HR, hazard ratio; ICER, incremental cost-effectiveness ratio; IRF, independent review facility; OS, overall survival; PFS, progression-free survival; QALY, quality-adjusted life year.

Figure 3. Cost-effectiveness acceptability curve (alloSCT eligible patients). AlloSCT, allogenic stem cell transplant; C/R, chemotherapy ± radiotherapy; QALY, quality-adjusted life year.

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