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*, Pieter Sonneveld, Carin A.Uyl de Groot

*Corresponding author for this work

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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.

Original languageEnglish
Article number591
JournalBMC Cancer
Issue number1
Early online date30 May 2022
Publication statusPublished - Dec 2022

Bibliographical note

Funding Information:
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.

Funding Information:
This work was supported by the European Myeloma Network EMN and a grant from ZonMw, the Netherlands Organisation for Health Research and Development, project number 152001020, project title “Treatment Sequencing in Multiple Myeloma: modeling the disease and evaluating cost-efficacy vs. cost-effectiveness”. The funding source had no role in writing the manuscript or decision to submit for publication. CvB is currently employed as contract worker at Amgen; however, all the analyses for this work have been conducted prior to initiating employment at Amgen. ZonMw,152001020

Publisher Copyright:
© 2022, The Author(s).


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