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

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