Obinutuzumab Plus Chemotherapy Compared with Rituximab Plus Chemotherapy in Previously Untreated Italian Patients with Advanced Follicular Lymphoma at Intermediate–High Risk: A Cost-Effectiveness Analysis

Figures & data

Figure 1 Model structure. Arrows indicate possible transitions through health states. “On treatment” and “Off treatment” are subcategories of health states included in PFS.

Abbreviations: PFS, progression-free survival; PD, progressive disease; Y 0–1, within 2 years; Y 2+, beyond 2 years.

Figure 2 Estimated survival curves based on GALLIUM study: Markov trace and time in health state.

Abbreviations: PFS, progression-free survival; PD, progressive desease; O-chemo, obinutuzumab and chemotherapy; R-chemo, rituximab and chemotherapy.

Table 1 Utility values

	Utility (95% CI)	Reference
PFS off treatment — induction	0.87 (0.85–0.90)	GALLIUM study^Citation20,Citation26
PFS off treatment — maintenance and follow-up	0.91 (0.90–0.92)
PFS on treatment — induction	0.90 (0.89–0.92)
PFS on treatment — maintenance and follow-up	0.91 (0.90–0.92)
PD, early progression	0.88 (0.86–0.90)
PD, late progression	0.88 (0.86–0.90)

Abbreviations: PFS, progression-free survival; PD, progressive disease.

Table 2 Costs of drugs, monitoring, adverse-event management, and postprogression therapy

Drugs
		Cost per vial	Reference
Obinutuzumab (1,000 mg vial)		€1,659.56	SORESA^Citation32
Rituximab SC branded (1,400 mg vial)		€1,219.18
Bendamustine unbranded (100 mg vial)		€19.58
Rituximab IV reference product (500 mg vial)		€992.00
Rituximab IV biosimilar (500 mg vial)		€272.50
Monitoring costs (follow-up from 30 months and during post-progression)
	Frequency (monthly)	Unit cost	Reference (frequency/cost)
Medical examination	13%	€20.66	AIOM^Citation7/Italian tariff^Citation34
CT	9%	€128.11
Blood exam	13%	€22.47
Average monthly cost (per patient)		€17.64
Postprogression costs
	Share	Overall cost	Reference (share/cost)
Allogeneic stem-cell transplant	0.9%	€86,448	EORTC study^Citation37/ Italian tariff^Citation34
Autologous stem-cell transplant	0.8%	€37,495
Chemotherapy	4.6%	€1,803
Anti-CD20 (combo)/other	55.0%	€10,194	Roche data on file^Citation33/SPC and SORESA^Citation32
Idelalisib monotherapy	30.0%	€20,767	Roche data on file^Citation33/Gopal et al^Citation39 and SORESA^Citation32
Lenalidomide-based regimen	5.0%	€54,171	Roche data on file^Citation33/Leonard et al^Citation40 and SORESA^Citation32
Radiotherapy	2.3%	€3,316	EORTC study^Citation37/AIMaC^Citation40 and Italian tariff^Citation34
No intervention	1.5%	—	EORTC study^Citation37
Average overall cost of progression (per patient)		€15,739.38
Adverse-event costs
		Cost (per event)	Reference
Anemia		€1,323	Mickisch et al^Citation41
Thrombocytopenia		€1,323
Leukopenia		€1,802
Neutropenia		€511
Febrile neutropenia		€4,824	Brown et al^Citation42
Dyspnea		€3,802	Italian tariff^Citation34 (weighted mean by SDO^Citation43)
Pneumonia		€3,194

Abbreviations: SC, subcutaneous; IV, intravenous; CT, computed tomography; SDO, Schede di Dimissione Ospedaliera.

Table 3 Base-case LYs, QALYs, and costs

	O-Chemo	R-Chemo	∆O-Chemo vs R-Chemo
Total LYs	14.31	13.35	0.97
In PFS	8.98	7.36	1.62
In progression	5.33	5.99	−0.65
Total QALYs	12.55	11.68	0.88
In PFS	8.03	6.58	1.45
In progression	4.52	5.10	−0.57
Overall costs (€)	40,477	25,503	14,974
PFS (€)	30,267	13,936	16,331
Anti-CD20 drug (€)	27,273	11,480	15,793
Chemotherapy (induction) (€)	215	211	4
Administration (€)	611	526	84
Adverse events (€)	743	615	128
Monitoring (€)	1426	1,104	321
PD cost* (€)	10,210	11,566	−1,356

Note: *Therapy and monitoring.

Abbreviations: LYs, life years; QALYs, quality adjusted LYs; PFS, progression-free survival; PD, progressive disease; O-chemo, obinutuzumab and chemotherapy; R-chemo, rituximab and chemotherapy.

Table 4 ICER and ICUR

	O-Chemo	R-Chemo	∆O-Chemo vs R-Chemo	ICER/ICUR
LYs	14.31	13.35	0.97	€15,516/LY gained
QALYs	12.55	11.68	0.88	€17,057/QALY gained
Mean costs (€)	40,477	25,503	14,974

Abbreviations: LYs, life-years; QALYs, quality-adjusted LYs; O-chemo; obinutuzumab and chemotherapy; R-chemo; rituximab and chemotherapy; ICER, incremental cost-efficacy ratio; ICUR, incremental cost-utility ratio.

Figure 3 Cost-effectiveness plane.

Abbreviations: O-chemo, obinutuzumab and chemotherapy; R-chemo, rituximab and chemotherapy.

Figure 4 Probability of being the most cost-effective treatment.

Abbreviations: O-chemo, obinutuzumab and chemotherapy; R-chemo, rituximab and chemotherapy.

Marcus R, Davies A, Ando K, et al. Obinutuzumab for the First-Line Treatment of Follicular Lymphoma. N Engl J Med. 2017;377(14):1331–1344. doi:10.1056/NEJMoa1614598

 PubMed Web of Science ®Google Scholar

Launonen A, Casulo C, Pott C, Rusconi C, Hernandez J, Davies A. Clinical outcomes of patients with intermediate‐to‐high‐risk follicular lymphoma (FL) in the Gallium phase III study. Hematol Oncol. 2019;37:386–387. doi:10.1002/hon.56_2631

 Google Scholar

SORESA. SORESA anagrafica beni (28-08-2020). Available from: www.soresa.it. Accessed April 8, 2020.

 Google Scholar

AIOM. Linee guida linfomi [Lymphoma guidelines]. Edizione 2018. Available from: https://www.aiom.it/linee-guida-aiom-2018-linfomi/. Accessed April 8, 2021.

 Google Scholar

Della Salute M. Remunerazione Prestazioni Di Assistenza Ospedaliera per Acuti, Assistenza Ospedaliera Di Riabilitazione e Di Lungodegenza Post Acuzie e Di Assistenza Specialistica Ambulatoriale. Decreto 10/2012 e pubblicato in GU Serie Generale n.23 del 28-1–2013.

 Google Scholar

van Oers MH, Van Glabbeke M, Giurgea L, et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin’s lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010;28(17):2853–2858. doi:10.1200/JCO.2009.26.5827

 PubMed Web of Science ®Google Scholar

Roche Market Research. Data On-File.

 Google Scholar

Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–1018. doi:10.1056/NEJMoa1314583

 PubMed Web of Science ®Google Scholar

Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: a Phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019;37(14):1188–1199. doi:10.1200/JCO.19.00010

 PubMed Web of Science ®Google Scholar

Mickisch G, Gore M, Escudier B, Procopio G, Walzer S, Nuijten M. Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: bevacizumab in combination with interferon-alpha2a compared with sunitinib. Br J Cancer. 2010;102(1):80–86. doi:10.1038/sj.bjc.6605417

 PubMed Web of Science ®Google Scholar

Brown B, Diamantopoulos A, Bernier J, et al. An economic evaluation of cetuximab combined with radiotherapy for patients with locally advanced head and neck cancer in Belgium, France, Italy, Switzerland, and the United Kingdom. Value Health. 2008;11(5):791–799. doi:10.1111/j.1524-4733.2007.00302.x

 PubMed Web of Science ®Google Scholar

Direzione generale della programmazione sanitaria - Ufficio 6. Ministero della Salute (2018). Rapporto annuale sull’attività di ricovero ospedaliero (SDO). Available from: https://www.salute.gov.it/portale/documentazione/p6_2_2_1.jsp?lingua=italiano&id=2898. Accessed July 2020.

 Google Scholar