Brentuximab vedotin in adult patients with HL CD30+ at high risk of relapse or progression following ASCT: a cost-analysis in Italy
DOI:
https://doi.org/10.33393/ao.2021.2263Keywords:
Brentuximab vedotin, Cost-analysis, Economic evaluation, Hodgkin Lymphoma, Italian NHSAbstract
Abstract
Introduction: In Hodgkin Lymphoma (HL), the early administration of brentuximab vedotin (BV) represents a highly effective treatment to consolidate patients after autologous stem cell transplantation (ASCT). For this indication, the Summary of Product Characteristics (SPC) reports a lower medical resource utilization in BV vs. placebo. This study aimed at assessing costs accrued by using BV in consolidation after ASCT and compare them with the resource consumption associated with the main options today used in Italy for HL.
Methods and results: A cost-analysis based on patients at high risk of relapse (HL CD30+-HR) after ASCT was developed by collecting data about health care consumption (drugs and monitoring). The model is described by two arms, "A," where BV is used as consolidation therapy after ASCT, and "B", where patients are treated only at the time of relapse. A 3-year time horizon and the Italian National Health System perspective were adopted. All data inputs for the analysis were sourced from the available literature and official list prices. The simulation was integrated by sensitivity analysis. The introduction of BV as consolidation therapy would allow savings in terms of drug acquisition and resource consumption. Over a 3-year time frame, the Consolidation arm’s overall expenditure was 137,059€ vs. 225,418€ in the Non-consolidation arm. Early after the ASCT, BV administration guarantees a long period free from relapses (5-year PFS is not reached), thus reducing the clinical and economic burden of the subsequent therapies needed to treat further relapses.
Conclusions: The present pharmacoeconomic analysis shows that the introduction of BV as consolidation therapy after ASCT represents a sustainable expenditure for the National Healthcare System (NHS) and a cost-saving paradigm when compared with the drug mainly used for treating the relapses.
Downloads
References
de Leval L, Gaulard P. CD30+ lymphoproliferative disorders. Haematologica. 2010;95(10):1627-1630. https://doi.org/10.3324/haematol.2010.029256 PMID:20884717 DOI: https://doi.org/10.3324/haematol.2010.029256
AIRTUM. The burden of rare cancers in Italy. Riv. dell’Associazione Ital. di Epidemiol. (2016).
Coviello V, Buzzoni C, Fusco M, et al; AIRTUM Working Group. Survival of cancer patients in Italy. Epidemiol Prev. 2017;41(2)(suppl 1):1-244. PMID:28629213
Herrera AF, Moskowitz AJ, Bartlett NL, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018;131(11):1183-1194. https://doi.org/10.1182/blood-2017-10-811224 PMID:29229594 DOI: https://doi.org/10.1182/blood-2017-10-811224
Lapuz C, Enjeti AK, O’Brien PC, Capp AL, Holliday EG, Gupta SA. Outcomes and relapse patterns following chemotherapy in advanced Hodgkin lymphoma in the positron emission tomography era. Blood Lymphat Cancer. 2018;8:13-20. https://doi.org/10.2147/BLCTT.S160404PMID:31360090 DOI: https://doi.org/10.2147/BLCTT.S160404
Eichenauer DA, Aleman BMP, André M, et al. Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29:iv19-iv29. https://doi.org/10.1093/annonc/mdy080 DOI: https://doi.org/10.1093/annonc/mdy080
Bazarbachi A, Boumendil A, Finel H et al, Evolution of outcome over time for relapsed Hodgkin lymphoma after autologous stem cell transplant: Improved survival for early relapse in recent years. Blood. 2020;136(Supplement 1):9-10. https://doi.org/10.1182/blood-2020-138546 DOI: https://doi.org/10.1182/blood-2020-138546
Arai S, Fanale M, DeVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54(11):2531-2533. https://doi.org/10.3109/10428194.2013.798868 PMID:23617324 DOI: https://doi.org/10.3109/10428194.2013.798868
EMA, E. Allegato I Riassunto delle caratteristiche del prodotto, Adcetris. (2018). https://ec.europa.eu/health/documents/community-register/2018/20180910142228/anx_142228_it.pdf
Moskowitz CH, Nademanee A, Masszi T, et al; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385(9980):1853-1862. https://doi.org/10.1016/S0140-6736(15)60165-9 PMID:25796459 DOI: https://doi.org/10.1016/S0140-6736(15)60165-9
Moskowitz CH, Walewski J, Nademanee A, et al. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018;132(25):2639-2642. https://doi.org/10.1182/blood-2018-07-861641 PMID:30266774 DOI: https://doi.org/10.1182/blood-2018-07-861641
AETHERA CSR, data on file
Caro JJ, Briggs AH, Siebert U, Kuntz KM; ISPOR-SMDM Modeling Good Research Practices Task Force. Modeling good research practices—overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force—1. Value Health. 2012;15(6):796-803. https://doi.org/10.1016/j.jval.2012.06.012 PMID:22999128 DOI: https://doi.org/10.1016/j.jval.2012.06.012
Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183-2189. https://doi.org/10.1200/JCO.2011.38.0410 PMID:22454421 DOI: https://doi.org/10.1200/JCO.2011.38.0410
Chen R, Gopal AK, Smith SE, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562-1566. https://doi.org/10.1182/blood-2016-02-699850 PMID:27432875 DOI: https://doi.org/10.1182/blood-2016-02-699850
Armand P, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II checkmate 205 trial. J Clin Oncol. 2018;36(14):1428-1439. https://doi.org/10.1200/JCO.2017.76.0793 PMID:29584546 DOI: https://doi.org/10.1200/JCO.2017.76.0793
AIFA. Agenzia Italiana del Farmaco. Regime di rimborsabilità e prezzo di vendita del medicinale per uso umano «Adcetris». Gazzetta n. 143 del 23 giugno 2014. Determina n. 607/2014.Determina 2018. https://www.gazzettaufficiale.it/eli/gu/2014/06/23/143/sg/pdf
AIFA. Agenzia Italiana del Farmaco. Regime di rimborsabilità e prezzo di vendita del medicinale per uso umano «Opdivo». Gazzetta n. 295 del. 17 dicembre 2019 Determina n. 1799/2019. (2019). https://www.gazzettaufficiale.it/eli/gu/2019/12/17/295/sg/pdf
Radford J, McKay P, Malladi R, et al. Treatment pathways and resource use associated with recurrent Hodgkin lymphoma after autologous stem cell transplantation. Bone Marrow Transplant. 2017;52(3):452-454. https://doi.org/10.1038/bmt.2016.244 PMID:28092356 DOI: https://doi.org/10.1038/bmt.2016.244
Younes A, Santoro A, Shipp M et al. Nivolumab for classical Hodgkin lymphoma after autologous stem-cell transplantation and brentuximab vedotin failure: a prospective phase 2 multi-cohort study. Lancet Oncol. 2016; 17(9): 1283-94. DOI: https://doi.org/10.1016/S1470-2045(16)30167-X
Cheah CY, Chihara D, Horowitz S, et al. Patients with classical Hodgkin lymphoma experiencing disease progression after treatment with brentuximab vedotin have poor outcomes. Ann Oncol. 2016;27(7):1317-1323. https://doi.org/10.1093/annonc/mdw169 PMID:27091808 DOI: https://doi.org/10.1093/annonc/mdw169
Alinari L, Blum KA. How I treat relapsed classical Hodgkin lymphoma after autologous stem cell transplant. Blood. 2016;127(3):287-295. https://doi.org/10.1182/blood-2015-10-671826PMID:26576863 DOI: https://doi.org/10.1182/blood-2015-10-671826
Gazzetta Ufficiale numero 156 del 7 Luglio 2006. Supplemento Ordinario n.161. https://www.gazzettaufficiale.it/eli/gu/2006/07/07/156/so/161/sg/pdf
Gazzetta Ufficiale numero 227 del 29 Settembre 2006. https://www.gazzettaufficiale.it/eli/gu/2006/09/29/227/sg/pdf
Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317(17):1098. https://doi.org/10.1056/NEJM198710223171717 PMID:3657876 DOI: https://doi.org/10.1056/NEJM198710223171717
Collins GP, Parker AN, Pocock C, et al; British Committee for Standards in Haematology; British Society of Blood and Marrow Transplantation. Guideline on the management of primary resistant and relapsed classical Hodgkin lymphoma. Br J Haematol. 2014;164(1):39-52. https://doi.org/10.1111/bjh.12582 PMID:24117159 DOI: https://doi.org/10.1111/bjh.12582
Ng M, Waters J, Cunningham D, et al. Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma. Br J Cancer. 2005;92(8):1352-1357. https://doi.org/10.1038/sj.bjc.6602514 PMID:15812553 DOI: https://doi.org/10.1038/sj.bjc.6602514
El Gnaoui T, Dupuis J, Belhadj K, et al. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007;18(8):1363-1368. https://doi.org/10.1093/annonc/mdm133PMID:17496309 DOI: https://doi.org/10.1093/annonc/mdm133
Selby P, Patel P, Milan S, et al. ChlVPP combination chemotherapy for Hodgkin’s disease: long-term results. Br J Cancer. 1990;62(2):279-285. https://doi.org/10.1038/bjc.1990.278PMID:2386744 DOI: https://doi.org/10.1038/bjc.1990.278
Heider A, Niederle N. Efficacy and toxicity of bendamustine in patients with relapsed low-grade non-Hodgkin’s lymphomas. Anticancer Drugs. 2001;12(9):725-729. https://doi.org/10.1097/00001813-200110000-00003 PMID:11593053 DOI: https://doi.org/10.1097/00001813-200110000-00003
Diehl V, Sieber M, Rüffer U et al; German Hodgkin's Lymphoma Study Group. BEACOPP: an intensified chemotherapy regimen in advanced Hodgkin's disease. The German Hodgkin's Lymphoma Study Group. Ann Oncol. 1997;8(2):143-148. https://doi.org/10.1023/A:1008294312741 DOI: https://doi.org/10.1023/A:1008294312741
Josting A, Rudolph C, Reiser M, et al; Participating Centers. Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin’s disease. Ann Oncol. 2002;13(10):1628-1635. https://doi.org/10.1093/annonc/mdf221 PMID:12377653 DOI: https://doi.org/10.1093/annonc/mdf221
NICE. Single Technology Appraisal Brentuximab vedotin for treating CD30-positive Hodgkin's lymphoma. Committee Papers [ID722]. (2016).
Regione Emilia Romagna. Tariffa unica convenzionale per le prestazioni di assistenza ospedaliera regole e tariffe valide per l’anno 2009 secondo cms-drg versione 24. (2009). https://salute.regione.emilia-romagna.it/siseps/sanita/sdo/files/tariffa_unica_conv_2009.pdf
Regione Emilia Romagna. Specifiche tecniche per l’applicazione delle tariffe n.317 del 30 ottobre 2014. https://bur.regione.emilia-romagna.it/area-bollettini/bollettini-in-lavorazione/n-317-del-30-10-2014-parte-seconda.2014-10-29.3572828660/at_download/pdf_firmato
Regione Lombardia. Deliberazione N° IX/2946, Seduta del 25 gennaio 2012. Tariffario prestazioni ambulatoriali. (2012). https://www.assolombarda.it/fs/20122115055_141.pdf
Regione Piemonte. Nomenclatore giugno 2013. (2013). http://www.regione.piemonte.it/sanita/cms2/component/phocadownload/category/68-nomenclatore-tariffario-regionale-delle-prestazioni-di-assistenza-specialistico-ambulatoriali.
Regione Puglia. Bollettino Ufficiale della Regione Puglia n. 94 del 16 luglio 2014. http://burp.regione.puglia.it/documents/10192/4815965/DELIBERAZIONE+DELLA+GIUNTA+REGIONALE+18+giugno+2014%2C%20n.+1202+%28id+4815978%29/7e51d73c-40f1-476d-9635-46a01a7f3537;jsessionid=FFAE47282A9BB27BF999A0EE22FCD5CB.
Nivolumab for treating relapsed or refractory classical Hodgkin lymphoma (ID972). Second appraisal committee meeting Chair's presentation. 12 April 2017 https://www.nice.org.uk/guidance/ta462/documents/1-2.
Lalibertè F, Raut M, Duh M, et al. Real-world healthcare resource utilization (HRU) of classical Hodgkin Lymphoma (cHL) patients (pts) treated with anti-PD1 checkpoint inhibitors in the United States (US). Hematol Oncol. 2019;37:495-496. https://doi.org/10.1002/hon.175_2631 DOI: https://doi.org/10.1002/hon.175_2631
Hoppe RT, Advani RH, Ai WZ, et al. NCCN guidelines® insights Hodgkin lymphoma, version 1.2018 featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2018;16(3):245-254. https://doi.org/10.6004/jnccn.2018.0013 DOI: https://doi.org/10.6004/jnccn.2018.0013
Bonafede M, Feliciano J, Cai Q, et al. Real-world analysis of cost, health care resource utilization, and supportive care in Hodgkin lymphoma patients with frontline failure. Clinicoecon Outcomes Res. 2018;10:629-641. https://doi.org/10.2147/CEOR.S178649 PMID:30410373 DOI: https://doi.org/10.2147/CEOR.S178649
Shao C, Liu J, Zhou W, et al. Treatment patterns, health care resource utilization, and costs in patients with relapsed/refractory Hodgkin lymphoma treated with brentuximab vedotin. Leuk Lymphoma. 2019;60(4):947-954. https://doi.org/10.1080/10428194.2018.1508665PMID:30234407 DOI: https://doi.org/10.1080/10428194.2018.1508665
Gazzetta Ufficiale, numero 23; 28 gennaio 2013; Supplemento n.8; Ministero della Salute. Tariffario prestazioni ambulatoriali. (2013). https://www.gazzettaufficiale.it/eli/id/2013/01/28/13A00528/sg
Ministero della salute. Rapporto annuale sull’attività di ricovero ospedaliero, Dati SDO 2017. http://www.salute.gov.it/portale/documentazione/p6_2_2_1.jsp?lingua=italiano&id=2831
Ministero della Salute 2007. Progetto Mattoni SSN. Pronto Soccorso e sistema 118. Proposta metodologica per la valutazione dei costi dell’emergenza. http://www.mattoni.salute.gov.it/mattoni/documenti/11_Valutazione_costi_dell_emergenza.pdf. (2007).
Vassilakopoulos TP, Chatzidimitriou C, Asimakopoulos JV, et al. Immunotherapy in Hodgkin lymphoma: present status and future strategies. Cancers (Basel). 2019;11(8):E1071. https://doi.org/10.3390/cancers11081071 PMID:31362369 DOI: https://doi.org/10.3390/cancers11081071
Sureda A, André M, Borchmann P, et al. Improving outcomes after autologous transplantation in relapsed/refractory Hodgkin lymphoma: a European expert perspective. BMC Cancer. 2020;20(1):1088. https://doi.org/10.1186/s12885-020-07561-2 PMID:33172440 DOI: https://doi.org/10.1186/s12885-020-07561-2
Brentuximab (Adcetris) for Hodgkin Lymphoma—Resubmission, pan-Canadian Oncology Drug Review Final Economic Guidance Report, Feb. 2018, https://www.cadth.ca/sites/default/files/pcodr/pcodr_brentuximab_adcetris_hl_post-asct_resub_fn_egr.pdf. (2018).
AIFA. Agenzia Italiana del Farmaco Regime di rimborsabilità e prezzo a seguito di nuove indicazioni terapeutiche del medicinale per uso umano «Keytruda». Gazzetta n. 290 del 27 novembre 2019. Determina n. 1763/2019.Determina 2019. (2019).
Yasenchak CA, Tseng WY, Yap M, Rembert D, Patt DA. Economic impact of disease progression following front-line therapy in classical Hodgkin lymphoma. Leuk Lymphoma. 2015;56(11):3143-3149. https://doi.org/10.3109/10428194.2015.1030639 PMID:25860233 DOI: https://doi.org/10.3109/10428194.2015.1030639
Hansen RN, Ramsey SD, Slejko J, Carlson JJ. The cost of relapse in Hodgkin lymphoma. J Clin Oncol. 2014;32(15 suppl):e17537. DOI: https://doi.org/10.1200/jco.2014.32.15_suppl.e17537
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2021 Gian Luca Breschi, Federica Demma, Paolo Morelli, Maria De Francesco
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors contributing to AboutOpen agree to publish their articles under the Creative Commons NonCommercial 4.0 International License (CC BY-NC 4.0), which allows third parties to copy and redistribute the material providing appropriate credit and a link to the license but does not allow to use the material for commercial purposes and to use the material if it has been remixed, transformed or built upon.
Accepted 2021-05-06
Published 2021-09-02
