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. 2022 May 30;22(1):591.
doi: 10.1186/s12885-022-09571-8.

Multinomial network meta-analysis using response rates: relapsed/refractory multiple myeloma treatment rankings differ depending on the choice of outcome

Chrissy H Y van Beurden-Tan  1 , Pieter Sonneveld  2 , Carin A Uyl-de Groot  3
Affiliations

Multinomial network meta-analysis using response rates: relapsed/refractory multiple myeloma treatment rankings differ depending on the choice of outcome

Chrissy H Y van Beurden-Tan et al. BMC Cancer. .

Abstract

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: 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: 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: 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.

Keywords: Multiple myeloma; Network meta-analysis; Response outcomes; SUCRA; Treatment ranking.

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Conflict of interest statement

Dr. Uyl-de Groot reports grants from Boehringer Ingelheim, Astellas, Celgene, Sanofi, Janssen-Cilag, Bayer, Amgen, Gemzyme, Merck, Gilead, Novartis, Glycostem Therapeutics, Astra Zeneca, and Roche, outside the submitted work. Dr. Sonneveld reports research support from Amgen, Celgene, Janssen, Karyopharm, and SkylineDx, reports participation in advisory boards of Amgen, Celgene, Genentech, Janssen, Karyopharm, and SkylineDx, outside the submitted work. Van Beurden-Tan is full-time employed as contract worker at Amgen since November 1st, 2018, reports no grants and research funding, no consultancies, no travel grants, no speaking fees, no writing fees and other honoraria, outside the submitted work.

Figures

Fig. 1
Fig. 1
Network of relapsed/refractory MM RCTs used for the multinomial network meta-analysis based on response. Legend: format of dark grey results box = `RCT name’: %CR/%PR/% < PR (N = `total number of patients’), * indicates estimated from other values, and black box indicates the reference treatment. Abbreviations: WB WinBUGS, NMA result, Bo bortezomib, Dex dexamethasone, Tha thalidomide, Car carfilzomib, Obl oblimersen, Dara daratumumab, Len lenalidomide, Pom pomalidomide, Ixa ixazomib, Elo elotuzumab, Pano panobinostat, Vorino = vorinostat, PLD pegylated liposomal doxorubicin
Fig. 2
Fig. 2
Forest plot of NMA results proportion of complete response patients. The treatments are ranked from highest to lowest, with the best treatment on top. Abbreviations: Bor bortezomib, Car carfilzomib, Dara daratumumab, Dex dexamethasone, Elo elotuzumab, Ixa ixazomib, Len lenalidomide, Obl oblimersen, Pano panobinostat, PLD pegylated liposomal doxorubicin, Pom pomalidomide, Thal thalidomide, Vorino vorinostat
Fig. 3
Fig. 3
Forest plot of NMA results proportion of objective response patients. The treatments are ranked from highest to lowest, with the best treatment on top. Abbreviations: Bor bortezomib, Car carfilzomib, Dara daratumumab, Dex dexamethasone, Elo elotuzumab, Ixa ixazomib, Len lenalidomide, Obl oblimersen, Pano panobinostat, PLD pegylated liposomal doxorubicin, Pom pomalidomide, Thal thalidomide, Vorino vorinostat
Fig. 4
Fig. 4
CRR ranking versus PFS ranking. Comparing the ranking of RRMM treatment combinations of binomial NMA of PFS HR NMA versus multinomial NMA of CRR
Fig. 5
Fig. 5
ORR ranking versus PFS ranking. Comparing the ranking of RRMM treatment combinations of binomial NMA of PFS HR NMA versus multinomial NMA of ORR
See this image and copyright information in PMC

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