ECP for CTCL

Home , Vorinostat

METHODS ► ► ► ► Transition Probabilities ► ► ► ► ► ► ► Model Structure ► ► Intervention and comparators ► Population ► ► ► ► ► Costs of of the Australian health care system. or more systemic treatments from the perspective T therapy for the treatment of erythrodermic (stage (ECP) compared withstandard of care (SoC) effectiveness of extracorporeal photopheresis in Australia.[1] estimated there are less than 1,200 CTCL patients plaques that significantly impact quality of life. It is causes debilitating pruritus, skin lesions and incurable form of non The objective of this study was to assess the cost therapies.[5, 8 3 or 4 AEs included in the model, given the number of Grade event (AE) costs wereconservatively not information sheets and international guidelines. treatment regimens as indicated in product thereafter. months, then one treatment everysixweeks consecutive days of treatment per month for six is based on international guidelines [6]:Two Pharmaceuticals plc, Bedminster, NJ, USA). methoxsalen, UVADEX® (Mallinckrodt procedure plus the cost of extracorporeal economic analysis. 2019 and the VCCCreport.[2] survival(OS) analysis for ECPpresented in Gao ECPand comparator treatments (Figure 3).[2] sourced from an Australian observational study of time in each health state for each therapy, was prescribing data. treatment surveyand Services Australia comparator arm was calculated based on weighted SoC comparator. Weighting of each time horizon. treatment at monthly cycle intervals overa 5 adjusted life years (QALYs) associated with each and product information sheets.[3,4] calculated using relevant treatment guidelines (Figure 2). validated using a Markov trace of the ECParm expensive) (Figure 1). cost of treatment (i.e. cheapest to most a fixed sequence of treatments determined by discontinuation of initial treatment, patients follow therapies before chemotherapy or no treatment. modelled to cycle through different 2 chemotherapy.[2] Therefore, patients were second IFN SoC therapies available in Australia (e.g. MTX, brentuximab vedotin (BV). interferon therapies including methotrexate (MTX), ECPand the comparator therapies. wasconducted to determine the placement of one or more systemic treatments. aged 18 years and older whoare refractory to T Results werepresented comparing ECPvs a Patients were assigned costs (in A$) and quality Monthly treatment regimens for therapy were Treatment sequence and model structure was The model assumes that following Patients with CTCL often cycle through multiple Cost Comparator was Standard of Care second A surveyand assessment of published literature P Cutaneous T Other Other costs such as treatment Drug costs weresourced from the PBS, and The ECPtreatment protocol applied in the model The cost of ECP included the cost of the ECP Only treatment costs were considered in this Baseline mortality was based on the overall cost cost per cycle calculated using the respective ‒ The Australian regimen has been shown to ‒ The ECPregimen used in Australia differs ‒ ‒ ‒ In the absence of progression free survival ‒ ‒ Patients received ECPtherapy at a median 2 ‒ T ‒ 4 ime to next treatment (TTNT) used to calculate atients atients with erythrodermic Stage T , , M The IFN TTNT provides a functional and clinically Conservatively, no survival benefit was Patients Patients received chemotherapy once all other similar. protocol [7] and the average cost per month is produce similar outcomes as the international individual hospitals and lack of resources.[7] due to complex funding arrangements in slightly from international guidelines primarily Median OS was 80 months. reported for ECPapplied to all treatment arms. assigned to the ECParm and mortality versus 8 months, respectively).[2] to the median TTNT for IFN treatment in the BV clinical trial [5] was similar source wasunavailable and the mean time on discontinuing givenBV that a KMBV curve proxy to calculate the probability of construct Kaplan (VCCC; Melbourne, VIC, AUS) was used to Victorian Comprehensive Cancer Centre associated unpublished data collected from the data, debilitating symptoms. implies durability of response and control of relevant measure of therapy effectiveness, as it line of treatment. Australian public payer. the model is from the perspective of the active therapy. it is assumed patients no longer received treatment options wereexhausted, after which he study had the highest external validity as - α - 0 OBJECTIVE BACKGROUND AND METHODS effectiveness of ECPcompared with other ) CTCL) patients, who are refractory to one vorinostat and BV). - TTNT data presented in Gao 2019 and line therapies as well as - - alpha (IFN α associated with - TTNT KM curve was used as a cell cell lymphoma (CTCL) is a rare and - 11] - [2] Meier (KM) curves.[2] - - Hodgkin’s lymphoma that α ), ), vorinostat, and comparator - - α related adverse (8.9 (8.9 months 4 nd , M line 0 CTCL - line - year nd 1 F Dehle LYMPHOMAPATIENTS INTHEAUSTRALIAN SETTING ERYTHRODERMIC (STAGE T PHOTOPHERESIS FOR THETREATMENT OF COST - Health Technology Analysts, Sydney,NSW, Australia, - ECP,extracorporeal photopheresis; ICER, incremental cost incremental; TTNT, time to next treatment, QALY, quality adjusted life years BV, brentuximab vedotin; CTCL, cutaneous T Monthly cost byof BV discounted 50% Use vorinostat TTNT for BV treatment associated disutility withNo Gao 2019 ECPtreatment regimen rate Discount 3.5% rate Discount 0% Base case Description data from data from the Gao 2019 study Pharmaceutical Benefits Scheme; TGA, Therapeutic Goods Administration; TTNT, time to next treatment BV, brentuximab vedotin; ECP, extracorporeal photopheresis; IFN, interferon; MSAC, Medical Services Advisory Committee; NA, n Discounting Time horizon treatment No Chemotherapy BV Vorinostat IFN Methotrexate ECP treatment No Chemotherapy BV Vorinostat IFN Methotrexate ECP treatment No Chemotherapy Brentuximab Vorinostat IFN Methotrexate ECP Chemotherapy BV Vorinostat IFN Methotrexate ECP Variable description Weighted Weighted comparator ECP Txarm BV,ECP,MTX,vedotin;methotrexate brentuximab interferon; IFN, photopheresis; extracorporeal BV, brentuximab vedotin; Chemo, chemotherapy; ECP, extracorporeal photopheresis; IFN, interferon; MTX, methotrexate; Non BV, ECP,Tx, MTX,methotrexate;chemotherapy; Chemo, interferon; vedotin;IFN, brentuximab photopheresis; extracorporeal Figure 3. Inputs used in the economic analysis Figure 4. ofResults the economic analysis Figure 5. ofResults deterministic sensitivityanalyses % health state Figure 2. the trace ofMarkov ECP arm 100% Figure 1. ofStructure the economic evaluation - - - - 10% 20% 30% 40% 50% 60% 70% 80% 90% 1 α α α α ECP arm Vorinostat arm BV arm MTX arm MTX IFN 0% , Gennari F , Gennari - - α 1 % ECP- EFFECTIVENESS OF EXTRACORPOREAL arm VIRTUAL ISPOR CONFERENCE MAY VIRTUALISPOR CONFERENCE 18 7 % MTX- Vorinostat 2 IFN nd MTX 2 ECP BV 13 , Peacock , Peacock A line 3 line % IFN- - $183,106 $145,514 α Costs - cell lymphoma; ECP,extracorporeal photopheresis; ICER, incremental cost 19 % Vorinostat- Vorinostat Vorinostat Incr. cost ------$27,507 $37,592 $31,642 $37,893 $38,512 $37,592 Median Median TTNT(Months) Month Month 1 to 5: $4,448.50 IFN $3,645 Costmonth per (AU$) IFN IFN rd MTX - MTX MTX effectiveness ratio; Incr, incremental; NA, not applicable;QALY, qual Month Month 6+: $1,611.92 line 4 line - - $37,591.99 - - Incr. cost 25 α α α $21,779.57 $4,519.20 $1,383.19 Disutility NA 1 $698.57 Cycle 5 5 years $13.67 - - - - Utility Other Value , Taylor C 0.058 0.018 0.095 0.040 0.59 0.59 0.68 0.65 0.70 0.62 0.73 % BV- 5% 7.5 2.5 NA NA NA $0 14 8 Incr. QALY 3 8 a 31 0.20 0.21 0.17 0.20 0.21 0.22 0.20 Vorinostat Vorinostat Chemo Chemo Chemo th % Chemotherapy- BV BV BV line 5 line QALYs 37 2.13 2.33 Dominant Dominant Dominant Dominant Dominant Dominant Dominant ICER 1 , Mesa Zapata OA Zapata , Mesa a assumed assumed same as IFN; 43 2 Chemo Chemo Chemo Chemo Chemo Mallinckrodt Pharmaceuticals, Bedminster,Pharmaceuticals, Mallinckrodt NJ, USA BV % No- treatment Incr. QALYs 4 Low Low Low - PBS; expert opinion PBS; expert opinion 20, 2020 20, , M o t o 0.20 NA Moderate Moderate reatment Low Low 49 PBS; TGA PI PBS; TGA PI - - - Assumption [12, [12, 14, 15] th Favours comparator Favours comparator Favours comparator PBS;[3] PBS;[4] Source [12, [12, 17] [12, 16] comparator line + line + MSAC [8, [8, 10] [5, 12] [7, 12] [5, [5, 11] - - - effectivenes [12] [12] [2] Impact Favours ECP Favours ECP [9] [9] b ot including including unpublished NA b applicable; applicable; PBS, O Chemo ity adjusted life years - 55 No TxNo No TxNo TxNo No TxNo % Dead- No TxNo Favours ) CUTANEOUS) T Dominant s ratio; Incr. ICER NA 61 2 ► Sensitivityanalysis ► ► ► ► ► Utilities ► ► ► ► 17. 16. 15. 14. 13. 12. 11. 10. 9. 8. 7. 6. 5. 4. 3. 2. 1. ► ‒ The price of BV examined given its confidential ‒ Vorinostat TTNT was applied to the arm. BV ‒ Disutilities wereremoved ‒ Australian approved ECPtreatment regimen ‒ Discounting at 0% and 3% following assumptions and scenarios were tested: plausible scenarios on the projected outcome. The assess the impact of various assumptions and other under the assumption of no response to treatment. disutility applied to the ECParm.[2] ECPtreatment in the Gao study, there wasno 8 using clinical evidence and existing publications.[5, and calculated based on frequency and severity 3 and 4 and AEs, therefore disutilities were applied ‒ Psoriasis severity wasmapped to CTCL treatment ‒ One psoriasis QOL study [12] was the most ‒ A clinician survey identified psoriasis as the most withCTCL. anyrelevant publications of utility values associated ► Deterministic sensitivity analysis was conducted to No disutility was applied to the chemotherapy arm Given that no Grade 3 or 4 AEs wereattributed to All comparator therapies are associated with Grade Weighted utility values for each treatment were A systematic review of the literature did not identify that that no response wasachieved withchemotherapy. clinical evidence.[5, 7, 12, 14 calculated based on responder rates reported in the 2015. 2015. 33(32): p. 3750 Expression Multi A Level: Vedotin in Mycosis Fungoides and SyndromeSezary CD30 With Variable lymphoma. Journal Oncology, Clinical of 2007. 25(21): p. 3109 with persistent, progressive, or treatment refractory cutaneous t fungoides and Sezary syndrome. Blood, 2016. 127(25): p. 3142 Treat, 2018. 29(5): p. 522 of treatments systemic for cutaneous T review, Health Technology Assessment, Editor. 2006: NHS. Etanercept and efalizumab for the treatment psoriasis: of a systematic Vergel, Misso, Y.,K., Light., Chalmers, R., Sculpher, M.,R.,, Riemsma, quantitative, utility approach. Arch Dermatol, 1995. 131(5): p. 561 p. 1839 systemic anaplastic large lymphoma.cell Leuk Lymphoma, 2015. 56(6): and adverse events relapsed/refractoryin Hodgkin lymphomaand 2018: p. 1 lymphoma:Hodgkin's United a States payer perspective. MedJ Econ, brentuximab vedotin for patients with relapsed or refractory classical treatment. Oncol, J 2001. Clin 19(3): p. 812 Netherlands. Clin Ther, 2017. 39(2): p. 288 Acute Treatment and Prevention Venous of Thromboembolism the in 2008. 59(4): p. 589 syndromeSezary a using treatmentnovel protocol. J Acad Dermatol,Am Photopheresis Society. journal British haematology,of 2017(pagination). transplant rejection: a consensus statement update from the UK of cutaneous T 390(10094): p. 555 label, randomised, phase 3, multicentre trial. The Lancet, 2017. positive cutaneous T 31(11): p. 1841 of the European AcademyDermatology of and Venereology, 2017. interferon alpha 2017, Pathway Group.Skin Blood, 2019. extracorporeal photopheresis regimen in patients Sézarywith Syndrome. Australas J Dermatol, 2015. challenges in assessment, management and prognostic markers. London London Cancer Gemcitabine Alliance, in Cutaneous T Gao, et C., al., Prolonged the with survival early use a novel of Kilbridge, Kilbridge, K.L., et al., Patient preferences for adjuvant interferon alfa de Jong, L.A., et al., Cost Hughes, C.F.,al., et Mycosis fungoides and Sezary syndrome: Current sensitivity analysis scenarios (Figure 5). comparator treatments. longer witha higher quality of life than and because patients remained on therapy for and 0.21, due to the lack of Grade 3 or 4 AEs adjusted life year (QALY)gain of between 0.20 vedotin). treatment options vorinostat and brentuximab avoided subsequent treatment with the high therapies (i.e. a greater proportion of patients 4). strategies in terms of cost for CTCL dominated over other treatment ECP is the dominant treatment option in all ECP wasassociated with an incremental quality ECP displaced expensivepharmaceutical Including ECP as a second ‒ Discounting monthly cost of byBV 50% had - Whittaker, Whittaker, R.Hoppe, S., and Prince, I H.M. Howtreat mycosis Large, et S., al., Cost Geskin, Geskin, L. and D.C. Malone, exploratory An cost Woolacott, N., Hawkins, N., Mason, A., Khadjesari, Kainth, A., Z., Bravo Zug, et K.A., the al., Assessing preferences of patients with psoriasis. A Arulogun, al., et S., Extracorporeal photopheresis for the treatment of Alfred The A, role extracorporeal of photopheresis in the management Prince, H.M., al., et Brentuximab vedotin or physician's choice CD30 in Schiller, M., al., et Dose both less costly and more effective. brentuximab vedotin, whichlead to ECPbeing treatment alternatives vorinostat and therapies and delayed advancing to high compared with other SoCtherapies. to one or more systemic treatments, in Australia, erythrodermic CTCL patients, whoare refractory effective option for the treatment of This analysis demonstrates that ECP is a cost Kim, Y.H., et al., Phase et Kim, Y.H.,Phase al., II Investigator Olsen, et E.A., al., multicenter Phase IIB trial vorinostat of in patients Swinburn, et P., al., Health in utilities relation to treatment response 11] ECPdisplaced expensive pharmaceutical effective price under the PBS. respectively. mapped to complete, partial and no response, response; mild, moderate and severe psoriasis the UK.[13] health technology assessments in Australia and appropriate as it had been applied in previous patients.[7] which are symptoms suffered byCTCL physical disfigurement and erythroderma; all of patients with psoriasis suffer from pruritis, have applicable disease to use as a proxy for QOL as comparator. ECPremained dominant over the weighted the greatest impact on the ICER, however, - 45. RESULTS REFERENCES CONCLUSION METHODS - 10. - - cell cell lymphoma,graft - 1847. 2a patients in with cutaneous T - - 95. 566. - cell lymphomacell international, (ALCANZA):an open - 8. - effectiveness effectiveness of pembrolizumab versus - - - Institution Institution Collaborative Oncol, Project. J Clin - 530. escalation escalation evaluating study pegylated effectiveness effectiveness Analysis for Apixaban in the - versus - - cell lymphoma.cell Dermatolog J - effectiveness (Figure Initiated Initiated Brentuximab Study of - line treatment option - - - - 17] 17] It wasassumed 302.e4. 23. host disease and organ - - cell lymphoma.cell Journal - effectiveness effectiveness analysis CELL - cell Lymphomacell - - cost cost - 3115. - cell cell 53. - - 8. cost cost - 2b - - - -