Cost-effectiveness analysis of KTE-X19 CAR T therapy versus real-world standard of care in patients with relapsed/refractory mantle cell lymphoma post BTKi in England

Figures & data

Table 1. Model input data and sources.

Model parameter	Value	Reference
KTE-X19 treatment costs ($)
KTE-X19	£316,118	Kite pharma list price
Leukapheresis	£1,521	NHS reference cost^34 (SA34Z and SA18Z)
Fludarabine (conditioning and bridging chemotherapy, £/admin)	£166.40	BNF^33
Cyclophosphamide (conditioning and bridging chemotherapy, £/admin)	£11.44	BNF^33
Standard of care treatment distributions^
Rituximab^a	56.7%	Based on the studies used in the literature-based meta-analysis^19
Venetoclax^b	12.7%
Bendamustine^c	35.0%
Bortezomib^d	6.4%
Lenalidomide^e	15.9%
Cytarabine^f	32.5%
Doxorubicin (Anthracycline)^g	3.2%
Standard of care acquisition costs (£/admin)
Rituximab	£705.49	BNF^33
Venetoclax	£8.55
Bendamustine	£11.73
Bortezomib	£39.15
Lenalidomide	£33.11
Cytarabine	£22.39
Doxorubicin (Anthracycline)	£5.13
Standard of care administration costs (£/admin)
Intravenous	£241.06	NHS reference cost^34 SB12Z
Hospitalization
KTE-X19: Intensive care unit (%)	22.7%	NICE axi-cel^25
KTE-X19: Non-intensive care unit (%)	77.3%	NICE axi-cel^25
KTE-X19: hospitalization duration (days)	21.2	ZUMA-2 trial
Hospitalization costs (£)
Intensive care unit	£1,428.09	NHS reference cost^34 XC01Z-XC07Z
Non-intensive care unit	£316.81	NHS reference cost^34 SA31A-F
Health state costs (£ per cycle)
Pre-progression	£349.76	Model calculations*
Pre-progression (long-term remission, ≥60 months progression-free)	£28.58	Model calculations*
Post-progression	£588.51	Model calculations*
End-of-life
Palliative care days	37	Bennett et al.^37
Palliative care cost per day	£447.00	Curtis and Burns^38
Adverse event costs (£)
KTE-X19	£12,691	Model calculations*
Standard of care	£0.00	Model calculations*
Health state utility values
Pre-progression	0.780	NICE ibrutinib, 2016^36
Pre-progression (long-term remission, ≥60 months progression-free)	0.805	Calculated from Ara and Brazier, 2010^39
Post-progression	0.680	NICE ibrutinib, 2016^36

^The treatment distributions for SoC sum to more than 100% as patients can be given combination treatment; ^aOne dose every 4-week cycle until progression or maximum 6 cycles; ^bDaily dose of venetoclax until progression, starting at 20 mg daily and ramping up weekly to 1,200 mg by week 7⁵; ^cTwo doses every 4-week cycle until progression or maximum 6 cycles; ^dFour doses every 3-week cycle for nine cycles or until progression; ^eDaily dose for 3 weeks every 4-week cycle until progression; ^fThree doses every 4-week cycle until progression or maximum 6 cycles; ^gOne dose every 3-week cycle until progression.

* Model calculations are outlined in Supplementary Table 3.

Figure 1. Model schematic.

Table 2. Base case results (discounted).

	KTE-X19	Standard of care	Incremental difference
Median overall survival	5.96	1.38	4.58
Total life years	8.27	1.98	6.29
Pre-progression	6.62	1.46	5.15
Post-progression	1.65	0.51	1.14
Total quality-adjusted life years	5.99	1.48	4.52
Pre-progression	4.99	1.13	3.85
Post-progression	1.06	0.34	0.72
Adverse events	−0.05	0.00	−0.05
Total costs	£385,765	£79,742	£306,023
Treatment-related costs
Drug acquisition	£316,118	£50,986	£265,132
Apheresis	£1,521	£0	£1,521
Drug administration	£4,652	£3,500	£1,152
Conditioning chemotherapy	£6,275	£0	£6,275
Bridging therapy	£373	£0	£373
Hospitalization	£12,064	£0	£12,064
Disease management costs
Pre-progression	£11,857	£5,973	£5,884
Post-progression	£11,652	£3,624	£8,028
Other costs
End of life care	£12,092	£15,659	-£3,567
Adverse events	£9,161	£0	£9,161
Cost per life years	£67,713	–	–
Cost per quality-adjusted life years	£48,645	–	–

Figure 2. Probabilistic cost-effectiveness plane.

Figure 3. Cost-effectiveness acceptability curves.

Figure 4. Univariate sensitivity analysis – influential parameters on incremental costs.

Figure 5. Univariate sensitivity analysis – influential parameters on incremental QALYs.

Figure 6. Univariate sensitivity analysis – influential parameters on the ICUR.

NHS. NHS National Reference Cost schedule 2018-19 2019. Available from: https://www.england.nhs.uk/national-cost-collection/#ncc1819.

 Google Scholar

British National Formulary. [Internet]; [cited 2021 Oct 8]. Available from: https://bnf.nice.org.uk.

 Google Scholar

Hess G, Dreyling M, Oberic L, et al. editors. KTE-X19 versus standard of care for relapsed/refractory mantle cell lymphoma previously treated with Bruton tyrosine kinase inhibitors: Real-World evidence from Europe. EHA; 2021.

 Google Scholar

NICE. Axicabtagene ciloleucel for treating diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma after 2 or more systemic therapies [ID1115]. 2018.

 Google Scholar

Bennett MI, Ziegler L, Allsop M, et al. What determines duration of palliative care before death for patients with advanced disease? A retrospective cohort study of community and hospital palliative care provision in a large UK city. BMJ Open. 2016;6(12):e012576.

 PubMed Web of Science ®Google Scholar

Curtis LA, Burns A. Unit Costs of Health and Social Care 2020; 2021. Available from: https://www.pssru.ac.uk/project-pages/unit-costs/unit-costs-2020/.

 Google Scholar

NICE. Ibrutinib for treating relapsed or refractory mantle cell lymphoma. Technology appraisal guidance [TA502] – Committee Papers. 2016.

 Google Scholar

Ara R, Brazier JE. Populating an economic model with health state utility values: moving toward better practice. Value Health. 2010;13(5):509–518.

 PubMed Web of Science ®Google Scholar

Eyre TA, Follows G, Hodson A, et al. Efficacy of venetoclax monotherapy in patients with relapsed, refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor therapy. haematologica. 2019;104(2):e71–e71.

 Web of Science ®Google Scholar