Abstract
Background
Treatments for multiple myeloma (MM) have been rapidly evolving. Newly developed treatment regimens are likely to be more effective but also cost more than conventional therapies.
Objective
We conducted a systematic review to compare the cost effectiveness of different classes of MM treatment.
Methods
We searched the PubMed, MEDLINE, Web of Science, and EMBASE databases for studies published during 1990–2018 comparing the cost effectiveness of transplant, chemotherapeutic and novel MM treatments. Titles and abstracts were independently reviewed for eligibility by two investigators. The quality of the included studies was evaluated using the 16-item, validated Quality of Health Economics Studies instrument.
Results
Twenty-four publications were included in the systematic review and summarized according to treatment regimen and line. For first-line treatment, transplant was the most cost-effective option for transplant-eligible MM patients [the incremental cost-effectiveness ratio (ICER) was $4053–€45,460 per quality-adjusted life-year (QALY) gained, and $3848–$72,852 per life-year gained (LYG)], and the ICER for novel agents compared with conventional chemotherapy was $59,076 per QALY and $220,681 per LYG. For second-line treatment, in comparisons of novel agent-based regimens, ICERs were inconsistent. However, bortezomib-based regimens, lenalidomide plus dexamethasone, and pomalidomide plus dexamethasone were each cost effective compared with dexamethasone alone (ICERs showed cost saving, £30,153 per QALY gained, and €39,911 per LYG, respectively).
Conclusions
For transplant-eligible MM patients, transplant is a cost-effective first-line treatment. More cost-effectiveness analyses comparing novel agents in the first-line treatment regimen are warranted to determine which agent or regimen is the most cost effective. In the second-line setting, it is unclear which novel agent-based regimen is most cost effective, but bortezomib-based regimens, lenalidomide plus dexamethasone, and pomalidomide plus dexamethasone were each cost effective compared with dexamethasone alone.
Similar content being viewed by others
References
Surveillance, epidemiology and end results program. Cancer Stat Facts: Myeloma. SEER; 2017.
American Society of Hematology. Myeloma; 2018. http://www.hematology.org/Patients/Cancers/Myeloma.aspx. Accessed 8 Apr 2018.
Kumar SK, et al. Multiple myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2017;15:230–69.
Naymagon L, Abdul-Hay M. Novel agents in the treatment of multiple myeloma: a review about the future. J Hematol Oncol. 2016;9:52.
Jemal A, et al. Annual Report to the Nation on the Status of Cancer, 1975–2014, featuring survival. J Natl Cancer Inst. 2017;109:djx030.
Kumar A, et al. Management of multiple myeloma: a systematic review and critical appraisal of published studies. Lancet Oncol. 2018;4:293–304.
Gaultney JG, et al. Critical review of economic evaluations in multiple myeloma: An overview of the economic evidence and quality of the methodology. Eur J Cancer. 2011;47(10):1458–67.
Zhang W, et al. Systematic review of cost-effectiveness analyses of treatments for psoriasis. PharmacoEconomics. 2015;33:327–40.
Chiou CF, et al. Development and validation of a grading system for the quality of cost-effectiveness studies. Med Care. 2003;41(1):32–44.
Henon PD, Donatini B, Eisenmann JC, Becker M, Beck-Wirth G. Comparative survival, quality of life and cost-effectiveness of intensive therapy with autologous blood cell transplantation or conventional chemotherapy in multiple myeloma. Bone Marrow Transplant. 1995;16(1):19–25.
Sampson FC, Beard SM, Scott F, Vandenberghe E. Cost-effectiveness of high-dose chemotherapy in first-line treatment of advanced multiple myeloma. Br J Haematol. 2001;113(4):1015–9.
Kouroukis CT, O’Brien BJ, Benger A, Marcellus D, Foley R, Garner J, et al. Cost-effectiveness of a transplantation strategy compared to melphalan and prednisone in younger patients with multiple myeloma. Leuk Lymphoma. 2003;44(1):29–37.
Prinja SK, Kaur G, Malhotra P, Jyani G, Ramachandran R, Bahuguna P, et al. Cost-effectiveness of autologous stem cell treatment as compared to conventional chemotherapy for treatment of multiple myeloma in India. Indian J Hematol Blood Transfus. 2017;33(1):31–40.
Garrison LP Jr, Wang ST, Huang H, Ba-Mancini A, Shi H, Chen K, et al. The cost-effectiveness of initial treatment of multiple myeloma in the U.S. with bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment. Oncologist. 2013;18(1):27–36.
Kim MY, Sposto R, Swaika A, Asano H, Alamgir A, Chanan-Khan A, et al. Pharmacoeconomic implications of lenalidomide maintenance therapy in multiple myeloma. Oncology. 2014;87(4):224–31.
Usmani SZ, Cavenagh JD, Belch AR, Hulin C, Basu S, White D, et al. Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma. J Med Econ. 2016;19(3):243–58.
Chen Y, Lairson DR, Chan W, Huo J, Du XL. Cost-effectiveness of novel agents in medicare patients with multiple myeloma: findings from a U.S. payer’s perspective. J Manag Care Spec Pharm. 2017;23(8):831–43.
Trippoli S, Messori A, Becagli P, Alterini R, Tendi E. Treatments for newly diagnosed multiple myeloma: analysis of survival data and cost-effectiveness evaluation. Oncol Rep. 1998;5(6):1475–82.
Corso A, Mangiacavalli S, Cocito F, Pascutto C, Ferretti VV, Pompa A, et al. Long term evaluation of the impact of autologous peripheral blood stem cell transplantation in multiple myeloma: a cost-effectiveness analysis [published erratum appears in PLoS One. 2014;9(1). doi:10.1371/annotation/949c27ad-65b0-4926-8c7b-5a45d67b1be9]. PLoS One. 2013;8(9):e75047.
Shah GL, Winn AN, Lin PJ, Klein A, Sprague KA, Smith HP, et al. Cost-effectiveness of autologous hematopoietic stem cell transplantation for elderly patients with multiple myeloma using the surveillance, epidemiology, and end results-medicare database. Biol Blood Marrow Transplant. 2015;21(10):1823–9.
Pandya C, Hashmi S, Khera N, Gertz MA, Dispenzieri A, Hogan W, et al. Cost-effectiveness analysis of early vs. late autologous stem cell transplantation in multiple myeloma. Clin Transplant. 2014;28(10):1084–91.
Mehta JD, Duff SB, Gupta S. Cost effectiveness of bortezomib in the treatment of advanced multiple myeloma. Manag Care Interface. 2004;17(9):52–61.
Hornberger J, Rickert J, Dhawan R, Liwing J, Aschan J, Lothgren M. The cost-effectiveness of bortezomib in relapsed/refractory multiple myeloma: Swedish perspective. Eur J Haematol. 2010;85(6):484–91.
Moller J, Nicklasson L, Murthy A. Cost-effectiveness of novel relapsed-refractory multiple myeloma therapies in Norway: lenalidomide plus dexamethasone vs bortezomib. J Med Econ. 2011;14(6):690–7.
Brown RE, Stern S, Dhanasiri S, Schey S. Lenalidomide for multiple myeloma: cost-effectiveness in patients with one prior therapy in England and Wales. Eur J Health Econ. 2013;14(3):507–14.
Fragoulakis V, Kastritis E, Psaltopoulou T, Maniadakis N. Economic evaluation of therapies for patients suffering from relapsed-refractory multiple myeloma in Greece. Cancer Manag Res. 2013;5:37–48.
Carlson JJ, Guzauskas GF, Chapman RH, Synnott PG, Liu S, Russo ET, et al. Cost-effectiveness of drugs to treat relapsed/refractory multiple myeloma in the United States. J Manag Care Spec Pharm. 2018;24(1):29–38.
Borg S, Nahi H, Hansson M, Lee D, Elvidge J, Persson U. Cost effectiveness of pomalidomide in patients with relapsed and refractory multiple myeloma in Sweden. Acta Oncol. 2016;55(5):554–60.
Pelligra CG, Parikh K, Guo S, Chandler C, Mouro J, Abouzaid S, et al. Cost-effectiveness of pomalidomide, carfilzomib, and daratumumab for the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma in the United States. Clin Ther. 2017;39(10):1986–2005.e5.
Gueneau P, Chretien ML, Cransac-Miet A, Aho LS, Lafon I, Favennec C, et al. Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma. Eur J Haematol. 2018;100(5):518–25.
Jakubowiak AJ, Campioni M, Benedict A, Houisse I, Tichy E, Giannopoulou A, et al. Cost-effectiveness of adding carfilzomib to lenalidomide and dexamethasone in relapsed multiple myeloma from a US perspective. J Med Econ. 2016;19(11):1061–74.
Jakubowiak AJ, Houisse I, Majer I, Benedict A, Campioni M, Panjabi S, et al. Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States. Expert Rev Hematol. 2017;10(12):1107–19.
Blommestein HM, Verelst SG, de Groot S, Huijgens PC, Sonneveld P, Uyl-de Groot CA. A cost-effectiveness analysis of real-world treatment for elderly patients with multiple myeloma using a full disease model. Eur J Haematol. 2016;96(2):198–208.
Zhang W, et al. Systematic review of cost-effectiveness analyses of treatments for psoriasis. Pharmacoeconomics. 2015;33(4):327–40.
Neumann PJ, Ganiats TG, Russell LB, Sanders GD, Siegel JE, Oxford University Press. Cost-effectiveness in health and medicine. New York: Oxford University Press; 2017.
Hay JW. Now is the time for transparency in value-based healthcare decision modeling. Value Health. 2019;22(5):564–9.
Aguiar PM, Lima TM, Storpirtis S. Systematic review of the economic evaluations of novel therapeutic agents in multiple myeloma: what is the reporting quality? J Clin Pharm Ther. 2016;41(2):189–97.
Chen W, Yang Y, Chen Y, Du F, Zhan H. Cost-effectiveness of bortezomib for multiple myeloma: a systematic review. Clinicoeconomics Outcomes Res. 2016;8:137–51.
Acknowledgements
The authors acknowledge the assistance with the literature search provided by Greg Pratt in the Research Medical Library, and the editorial services provided by Sarah Bronson in Scientific Publications at The University of Texas MD Anderson Cancer Center.
Author information
Authors and Affiliations
Contributions
SF: study concept and design, data collection and interpretation, and manuscript drafting and revision. CFW: data collection and interpretation, and manuscript drafting and revision. MW: data interpretation, and manuscript drafting and revision. DRL: study concept and design, data interpretation, and manuscript drafting and revision.
Corresponding author
Ethics declarations
Conflict of interest
Shuangshuang Fu, Chi-Fang Wu, Michael Wang and David R. Lairson have no conflicts of interest to declare.
Sources of funding
None.
Appendices
Appendix 1: Search strategy for the four databases
1. Search strategy for Medline
1 | MULTIPLE MYELOMA/ |
2 | multiple myeloma*.ti,kf,ab. |
3 | (plasma cell* adj3 myeloma*).ti,kf,ab. |
4 | Kahler* disease.ti,kf,ab. |
5 | or/1-4 |
6 | limit 5 to english language |
7 | limit 6 to yr=“1990 -Current” |
8 | exp “COSTS AND COST ANALYSIS”/ |
9 | ECONOMICS, PHARMACEUTICAL/ |
10 | MODELS, ECONOMIC/ |
11 | ECONOMICS, MEDICAL/ |
12 | (cost*3 adj5 (benefit* or analy* or control* or measur* or averag* or estimat* or evaluat* or annual* or minimiz* or minimis* or minimali* or utilit* or effectiveness or containment)).ti,kf. |
13 | (cost*3 adj3 (benefit* or analy* or control* or measur* or averag* or estimat* or evaluat* or annual* or minimiz* or minimis* or minimali* or utilit* or effectiveness or containment)).ab. /freq=3 |
14 | ((cost*3 or economic* or pharmacoeconomic* or pharmaco-economic*) and myeloma*).ti. |
15 | ((econom* or cost*3 or financ* or expenditure* or spend* or spent) adj5 (impact* or model* or evaluat* or analy* or burden)).ti,kf. |
16 | ((econom* or cost*3 or financ* or expenditure* or spend* or spent) adj3 (impact* or model* or evaluat* or analy* or burden)).ab. /freq=2 |
17 | QUALITY-ADJUSTED LIFE YEARS/ |
18 | “quality adjusted life year*”.ti,kf,ab. |
19 | (ICER or QALY).ti,kf,ab. |
20 | ((life adj year* adj2 gain*) or LYG).ti,kf,ab. |
21 | ((“progression free life” adj2 year*) or PFLY).ti,kf,ab. |
22 | or/8-21 |
23 | 7 and 22 |
24 | limit 23 to (editorial or letter) |
25 | 23 not 24 |
2. Search strategy for Embase
1 | *MULTIPLE MYELOMA/ |
2 | multiple myeloma*.ti,kw. |
3 | (plasma cell* adj3 myeloma*).ti,kw. |
4 | Kahler* disease.ti,kw. |
5 | (“multiple myeloma*” or “Kahler* disease” or (plasma cell* adj3 myeloma*)).ab. /freq=2 |
6 | or/1-5 |
7 | limit 6 to english language |
8 | limit 7 to yr=“1990 -Current” |
9 | exp ECONOMIC EVALUATION/ |
10 | PHARMACOECONOMICS/ |
11 | DRUG COST/ |
12 | *HEALTH-CARE-COST/ |
13 | *HEALTH-ECONOMICS/ |
14 | (cost*3 adj5 (benefit* or analy* or control* or measur* or averag* or estimat* or evaluat* or annual* or minimiz* or minimis* or minimali* or utilit* or effectiveness or containment)).ti,kw. |
15 | (cost*3 adj3 (benefit* or analy* or control* or measur* or averag* or estimat* or evaluat* or annual* or minimiz* or minimis* or minimali* or utilit* or effectiveness or containment)).ab. /freq=2 |
16 | ((cost*3 or economic* or pharmacoeconomic* or pharmaco-economic*) and myeloma*).ti. |
17 | ((econom* or cost*3 or financ* or expenditure* or spend* or spent) adj5 (impact* or model* or evaluat* or analy* or burden)).ti,kw. |
18 | ((econom* or cost*3 or financ* or expenditure* or spend* or spent) adj3 (impact* or model* or evaluat* or analy* or burden)).ab. /freq=2 |
19 | QUALITY-ADJUSTED LIFE YEAR/ |
20 | “quality adjusted life year*”.ti,kw,ab. |
21 | (ICER or QALY).ti,kw,ab. |
22 | ((life adj year* adj2 gain*) or LYG).ti,kw,ab. |
23 | ((“progression free life” adj2 year*) or PFLY).ti,kw,ab. |
24 | or/9-23 |
25 | 8 and 24 |
26 | limit 25 to (editorial or letter) |
27 | 25 not 26 |
28 | limit 27 to conference abstract |
29 | 27 not 28 |
3. Search strategy for PubMed excluding Medline
#11 | #3 and #10 |
#10 | #4 or #5 or #6 or #7 or #8 or #9 |
#9 | “progression free life year”[tiab] OR “progression free life years”[tiab] OR PFLY[tiab] |
#8 | “life year gain”[tiab] OR “life year gains”[tiab] OR “life year gained”[tiab] OR LYG[tiab] |
#7 | “quality adjusted life year”[tiab] OR “quality adjusted life years”[tiab] or ICER[tiab] OR QALY[tiab] |
#6 | ((cost[tiab] or costs[tiab] or economic*[tiab]) and myeloma*[ti] and (benefit*[tiab] or analys*[tiab] or analyz*[tiab] or control*[tiab] or measur*[tiab] or averag*[tiab] or estimat*[tiab] or evaluat*[tiab] or annual*[tiab] or minimiz*[tiab] or minimis*[tiab] or minimali*[tiab] or utilit*[tiab] or effectiveness[tiab] or containment[tiab])) |
#5 | ((“cost effective”[tiab] or “cost benefit”[tiab] or “cost utility”[tiab] or “economic evaluation”[tiab] or cost[ti] or costs[ti] or economic*[ti] or pharmacoeconomic*[ti] or pharmaco-economic*[ti]) and myeloma*[ti]) |
#4 | ((econom*[tiab] or cost[tiab] or costs[tiab] or financ*[tiab] or expenditure*[tiab] or spend*[tiab] or spent[tiab]) and myeloma*[ti] and (impact*[tiab] or model*[tiab] or evaluat*[tiab] or analy*[tiab] or burden[tiab])) |
#3 | #1 and #2 |
#2 | myeloma* |
#1 | publisher[sb] |
4. Search strategy for Web of Science
# 15 | (#13 not #14) ANDLANGUAGE: (English) |
# 14 | (#13) ANDLANGUAGE: (English) ANDDOCUMENT TYPES: (Meeting Abstract) |
# 13 | (#12 and py=1990-2018) ANDLANGUAGE: (English) |
# 12 | (#4 and #11) ANDLANGUAGE: (English) |
# 11 | (#5 or #6 or #7 or #8 or #9 or #10) ANDLANGUAGE: (English) |
# 10 | (ts=((“progression free life” NEAR/2 year*) or PFLY)) ANDLANGUAGE: (English) |
# 9 | (ts=((life adj year* NEAR/2 gain*) or LYG)) ANDLANGUAGE: (English) |
# 8 | (ts=(“quality adjusted life year” or “quality adjusted life years” or ICER or QALY)) ANDLANGUAGE: (English) |
# 7 | (ts=((econom* or cost* or financ* or expenditure* or spend* or spent) NEAR/5 (impact* or model* or evaluat* or analy* or burden))) ANDLANGUAGE: (English) |
# 6 | (ti=((cost* or economic* or pharmacoeconomic* or pharmaco-economic*) and myeloma*)) ANDLANGUAGE: (English) |
# 5 | (ts=(cost* NEAR/5 (benefit* or analy* or control* or measur* or averag* or estimat* or evaluat* or annual* or minimiz* or minimis* or minimali* or utilit* or effectiveness or containment))) ANDLANGUAGE: (English) |
# 4 | #2 not #3 |
# 3 | (#2) ANDDOCUMENT TYPES: (Editorial Material OR Letter) |
# 2 | (#1) ANDLANGUAGE: (English) |
# 1 | ts=(multiple myeloma*) |
Appendix 2: QHES assessment for each individual study
Study | Q1 | Q2 | Q3 | Q4 | Q5 | Q6 | Q7 | Q8 | Q9 | Q10 | Q11 | Q12 | Q13 | Q14 | Q15 | Q16 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Henon et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 |
Trippoli et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 |
Sampson et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 |
Kouroukis et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Mehta et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 |
Hornberger et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Moller et al. | 1 | 0 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Brown et al. | 1 | 0 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Corso et al. | 1 | 0 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Fragoulakis et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Garrison et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Kim et al. | 1 | 0 | 1 | NA | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 |
Pandya et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 |
Shah et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 |
Blommestein et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Borg et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 |
Jakubowiak et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Usmani et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Chen et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Jakubowiak et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Pelligra et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Prinja et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 |
Carlson et al. | 1 | 1 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
Gueneau et al. | 0 | 0 | 1 | NA | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 |
Rights and permissions
About this article
Cite this article
Fu, S., Wu, CF., Wang, M. et al. Cost Effectiveness of Transplant, Conventional Chemotherapy, and Novel Agents in Multiple Myeloma: A Systematic Review. PharmacoEconomics 37, 1421–1449 (2019). https://doi.org/10.1007/s40273-019-00828-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40273-019-00828-y