Cost-effectiveness of blinatumomab versus salvage chemotherapy in relapsed or refractory Philadelphia-chromosome-negative B-precursor acute lymphoblastic leukemia from a US payer perspective

Figures & data

Figure 1. The B-GEM schematic.

Table 1. Summary of model parameters.

Parameter	Point estimate	Distribution	SE	Source
Analytic variables
Timeframe (years)	50	Constant	n/a	Assumption
Annual discount rate, costs	3.0%	Constant	n/a	Sanders et al.^35 (2016)
Annual discount rate, effectiveness	3.0%	Constant	n/a
ICER threshold ($)	150,000	Constant	n/a	Assumption
Patient characteristics
Starting age (years)	40.9	Constant	n/a	TOWER
Percentage male	59%	Constant	n/a	TOWER
Efficacy
Response rate
Blinatumomab	43.9%	Bootstrap	n/a	TOWER
SOC	24.6%	Bootstrap	n/a	TOWER
EFS response distribution	Generalized gamma, restricted	Bootstrap	n/a	TOWER
OS distribution	Gompertz, restricted	Bootstrap	n/a	TOWER
Costs
Blinatumomab
Cost per vial ($)	3,464	Constant	n/a	Truven Health Analytics RED BOOK™^31
Days per bag change	2	Constant	n/a	Assumption
Inpatient days per cycle received
Cycle 1	9	Constant	n/a	BLINCYTO prescribing information
Cycle 2	2	Constant	n/a
Cycle 3+	0	Constant	n/a
Cost per inpatient day ($)	5,423	Lognormal	171	Barlev et al.^32 (2016)
Cost per day of HIT ($)	67	Lognormal	1.60	Blue Cross and Blue Shield of Michigan^33
Cost per outpatient visit ($)	139	Lognormal	16.5	Center for Medicare and Medicaid Services^34
SOC
Administration costs
Inpatient days per cycle received	10.8	Lognormal	2.6	Barlev et al.^32 (2016)
Cost per inpatient day ($)	5,423	Lognormal	171	Barlev et al.^32 (2016)
Other costs
Proportion receiving alloHSCT
Blinatumomab	24.0%	Beta	2.6%	TOWER
SOC	23.9%	Beta	3.7%	TOWER
Cost of alloHSCT ($)	350,126	Lognormal	15,023	Barlev et al.^32 (2016)
Subsequent salvage therapy
Proportion of patients receiving
Innovative anticancer therapy
Blinatumomab patients	5.2%	Beta	1.4%	TOWER
SOC patients	11.0%	0	0.0%	TOWER
Chemotherapy
Blinatumomab patients	24.7%	Beta	2.6%	TOWER
SOC patients	29.4%	Beta	4.4%	TOWER
Cost per course
Innovative anticancer therapy	262,601	^a	n/a	n/a
Chemotherapy	62,061	^a	n/a	n/a
Terminal care for patients not cured	25,624	Lognormal	2,150	Chastek et al.^38 (2012)
Utility values
Blinatumomab
Initial	0.766	Lognormal^b	0.018	TOWER
Response	0.814	Lognormal^b	0.019
Relapse/refractory	0.742	Lognormal^b	0.032
SOC
Initial	0.688	Lognormal^b	0.034
Response	0.747	Lognormal^b	0.038
Relapse/refractory	0.673	Lognormal^b	0.036
Terminal decrement	0.027	Lognormal	0.032
General population, male/female
18–29 years	0.922/0.922	Constant	n/a	Sullivan et al.^30 (2006)
30–39 years	0.901/0.901	Constant	n/a
40–49 years	0.871/0.871	Constant	n/a
50–59 years	0.842/0.842	Constant	n/a
60–69 years	0.823/0.823	Constant	n/a
70–79 years	0.790/0.790	Constant	n/a
80–100 years	0.736/0.736	Constant	n/a

^aCosts calculated in model.

^bSampled by sampling from disutility (1-utility), assuming disutility value is lognormal.

Figure 2. EFS among responders and OS in TOWER: Kaplan-Meier estimates and parametric survival distributions used in the B-GEM.

Figure 3. NMB of blinatumomab vs SOC based on ICER threshold of $150,000 per QALY gained. QALY, quality adjusted life year; R/R, relapsed/refractory; Allo-SCT, allogeneic hematopoietic stem cell transplantation; Subs., Subsequent, Tx, treatment; NMB, net monetary benefit. *Includes costs of drug acquisition and administration, including hospitalization, outpatient visits, and home infusion therapy.

Table 2. Base case results.

Outcomes	Blinatumomab	SOC	Incremental
Effectiveness, discounted
Life-years
Initial	0.20	0.19	0.01
Response	0.72	0.28	0.44
Relapse/refractory	3.78	2.31	1.47
Total	4.69	2.78	1.92
QALYs
Initial	0.15	0.13	0.02
Response	0.59	0.22	0.38
Relapse/refractory	3.08	1.83	1.24
Total	3.82	2.18	1.64
Costs, discounted, $
Salvage therapy (drug acquisition   and administration)	262,601	62,061	200,539
AlloHSCT	84,030	83,612	418
Subsequent salvage therapy	28,323	46,638	–18,315
Terminal care	20,140	22,140	–2,000
Total	395,094	214,452	180,642
Cost effectiveness, $per QALY
ICER			110,108
NMB by cost-effectiveness threshold, $
$150,000 per QALY gained			65,446
$200,000 per QALY gained			147,476

Table 3. Results of sub-group and scenario analyses.

#	Scenario	Blinatumomab			SOC			Blinatumomab vs SOC
		Cost ($)	Life-years	QALYs	Cost ($)	Life-years	QALYs	Cost	Life-years	QALYs	ICER ($)
	Base case (all patients FAS)	395,094	4.69	3.82	214,452	2.78	2.18	180,642	1.92	1.64	110,108
1	No prior salvage, FAS	466,869	5.38	4.40	248,776	2.80	2.18	218,092	2.58	2.22	98,378
2	Safety analysis set	405,659	4.21	3.28	249,473	2.43	1.80	156,186	1.78	1.48	105,736
3	EFS based on log-normal	395,492	4.69	3.82	214,733	2.78	2.18	180,759	1.92	1.64	110,315
4	36-month duration of benefit	395,095	4.61	3.76	214,452	2.78	2.18	180,643	1.84	1.58	114,575
5	60-month duration of benefit	395,090	4.72	3.85	214,452	2.78	2.18	180,638	1.95	1.66	108,514
6	30-year model timeframe	395,189	4.02	3.30	214,514	2.41	1.90	180,675	1.61	1.41	128,449
7	60-year model timeframe	395,072	4.73	3.85	214,438	2.80	2.20	180,635	1.93	1.65	109,250
8	Rate of alloHSCT from MT103-211	398,595	4.69	3.82	193,862	2.78	2.18	204,733	1.92	1.64	124,792
9	Zero cost for Blinatumomab cycle 6+	374,611	4.69	3.82	212,329	2.78	2.18	162,282	1.92	1.64	98,917
10	Cost of hospitalization for chemotherapy = $132,137 per stay (19.6 days per stay)	426,017	4.69	3.82	316,328	2.78	2.18	109,690	1.92	1.64	66,860
11	Equal post-relapse utilities for blinatumomab and SOC	395,094	4.69	3.78	214,452	2.78	2.18	180,642	1.92	1.60	112,853
12	Reduce general population utility values by 0.0285	395,094	4.69	3.72	214,452	2.78	2.13	180,642	1.92	1.60	113,174

FAS, full analysis set; EFS, event-free survival; OS, overall survival; RCS, restricted cubic spline; alloHSCT, allogeneic hematopoietic stem cell transplantation.

Figure 4. Tornado diagram showing results of deterministic sensitivity analyses on the cost-effectiveness of blinatumomab vs SOC. SOC, standard of care; Blin, blinatumomab; R/R, relapsed or refractory; EFS, event-free survival; Allo-SCT, allogeneic stem cell transplant; CR, complete response; CRh, complete response with partial hematologic recovery; CRi, complete response with partial or incomplete hematologic recovery.

Figure 5. Cost-effectiveness acceptability curves for blinatumomab and SOC.

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