Multinomial network meta-analysis using response rates: relapsed/refractory multiple myeloma treatment rankings differ depending on the choice of outcome.
Multiple myeloma
Network meta-analysis
Response outcomes
SUCRA
Treatment ranking
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
30 May 2022
30 May 2022
Historique:
received:
18
04
2021
accepted:
19
04
2022
entrez:
31
5
2022
pubmed:
1
6
2022
medline:
3
6
2022
Statut:
epublish
Résumé
Due to the fast growing relapsed/refractory multiple myeloma (RRMM) treatment landscape, a comparison of all the available treatments was warranted. For clinical practice it is important to consider both immediate effects such as response quality and prolonged benefits such as progression-free survival (PFS) in a meta-analysis. The objective of this study was to assess the impact of the choice of outcome on the treatment rankings in RRMM. A multinomial logistic network meta-analysis was conducted to estimate the ranking of sixteen treatments based on both complete and objective response rates (CRR and ORR). Seventeen phase III randomized controlled trials from a previously performed systematic literature review were included. Treatment ranking was based on the surface under the cumulative ranking curve (SUCRA). Sensitivity analysis was conducted. The ranking of treatments differed when comparing PFS hazard ratios rankings with rankings based on CRR. Pomalidomide, bortezomib and dexamethasone ranked highest, while a substantial lower ranking was observed for the triplet elotuzumab, lenalidomide, dexamethasone. The ranking of treatments did not differ when comparing PFS hazard ratios and ORR. The scenario analyses showed that the results were robust. In all scenarios the top three was dominated by the same triplets. The treatment with the highest probability of having the best PFS and ORR was the triplet daratumumab, lenalidomide plus dexamethasone in the base case. This analysis shows that depending on the chosen outcome treatment rankings in RRMM may differ. When conducting NMAs, the response rate, a clinically recognized outcome, should therefore be more frequently considered.
Sections du résumé
BACKGROUND
BACKGROUND
Due to the fast growing relapsed/refractory multiple myeloma (RRMM) treatment landscape, a comparison of all the available treatments was warranted. For clinical practice it is important to consider both immediate effects such as response quality and prolonged benefits such as progression-free survival (PFS) in a meta-analysis. The objective of this study was to assess the impact of the choice of outcome on the treatment rankings in RRMM.
METHODS
METHODS
A multinomial logistic network meta-analysis was conducted to estimate the ranking of sixteen treatments based on both complete and objective response rates (CRR and ORR). Seventeen phase III randomized controlled trials from a previously performed systematic literature review were included. Treatment ranking was based on the surface under the cumulative ranking curve (SUCRA). Sensitivity analysis was conducted.
RESULTS
RESULTS
The ranking of treatments differed when comparing PFS hazard ratios rankings with rankings based on CRR. Pomalidomide, bortezomib and dexamethasone ranked highest, while a substantial lower ranking was observed for the triplet elotuzumab, lenalidomide, dexamethasone. The ranking of treatments did not differ when comparing PFS hazard ratios and ORR. The scenario analyses showed that the results were robust. In all scenarios the top three was dominated by the same triplets. The treatment with the highest probability of having the best PFS and ORR was the triplet daratumumab, lenalidomide plus dexamethasone in the base case.
CONCLUSION
CONCLUSIONS
This analysis shows that depending on the chosen outcome treatment rankings in RRMM may differ. When conducting NMAs, the response rate, a clinically recognized outcome, should therefore be more frequently considered.
Identifiants
pubmed: 35637452
doi: 10.1186/s12885-022-09571-8
pii: 10.1186/s12885-022-09571-8
pmc: PMC9150316
doi:
Substances chimiques
Dexamethasone
7S5I7G3JQL
Lenalidomide
F0P408N6V4
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
591Subventions
Organisme : ZonMw
ID : 152001020
Pays : Netherlands
Informations de copyright
© 2022. The Author(s).
Références
Blood. 2016 Jun 9;127(23):2833-40
pubmed: 27091875
Br J Haematol. 1998 Sep;102(5):1115-23
pubmed: 9753033
J Clin Oncol. 2012 Jul 10;30(20):2475-82
pubmed: 22585692
Lancet. 2015 May 30;385(9983):2197-208
pubmed: 25540889
Blood Adv. 2017 Feb 27;1(7):455-466
pubmed: 29296961
Haematologica. 2012 May;97(5):784-91
pubmed: 22133776
Clin Ther. 2018 Mar;40(3):480-494.e23
pubmed: 29500140
J Manag Care Spec Pharm. 2018 Jan;24(1):29-38
pubmed: 29290170
N Engl J Med. 2015 Jan 8;372(2):142-52
pubmed: 25482145
N Engl J Med. 2003 Jun 26;348(26):2609-17
pubmed: 12826635
N Engl J Med. 2007 Nov 22;357(21):2123-32
pubmed: 18032762
N Engl J Med. 2007 Nov 22;357(21):2133-42
pubmed: 18032763
Pharmacoeconomics. 2018 Sep;36(9):1073-1081
pubmed: 29582405
N Engl J Med. 2005 Jun 16;352(24):2487-98
pubmed: 15958804
Cancer. 2016 Jul 1;122(13):2050-6
pubmed: 27191689
Leukemia. 2009 Jan;23(1):3-9
pubmed: 18971951
Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):163-173.e6
pubmed: 29456035
Blood. 2009 Apr 9;113(15):3435-42
pubmed: 18955563
N Engl J Med. 2016 Aug 25;375(8):754-66
pubmed: 27557302
Am J Hematol. 2015 Jan;90(1):42-9
pubmed: 25294016
Value Health. 2010 Dec;13(8):976-83
pubmed: 20825617
Leuk Lymphoma. 2009 Apr;50(4):559-65
pubmed: 19373653
Lancet Oncol. 2013 Oct;14(11):1129-1140
pubmed: 24055414
Lancet Oncol. 2016 Jan;17(1):27-38
pubmed: 26671818
Cancer. 2013 Jan 15;119(2):339-47
pubmed: 22811009
Lancet Oncol. 2014 Oct;15(11):1195-206
pubmed: 25242045
Eur J Haematol. 2012 Jun;88(6):485-96
pubmed: 22404182
Leukemia. 2006 Sep;20(9):1467-73
pubmed: 16855634
Blood. 2011 May 5;117(18):4691-5
pubmed: 21292775
Lancet Oncol. 2013 Oct;14(11):1055-1066
pubmed: 24007748
N Engl J Med. 2015 Aug 13;373(7):621-31
pubmed: 26035255
Cancer Chemother Rep 3. 1968 Dec;1(1):17-39
pubmed: 4195760
BMC Med Res Methodol. 2018 Jun 28;18(1):66
pubmed: 29954322
Leuk Lymphoma. 2019 Jan;60(1):151-162
pubmed: 30407092
Cancer Manag Res. 2018 Aug 21;10:2817-2823
pubmed: 30174457
Lancet Oncol. 2019 Jun;20(6):781-794
pubmed: 31097405
J Clin Oncol. 2017 Apr 20;35(12):1312-1319
pubmed: 28240968