OBJECTIVES: Owing to the rapidly-evolving landscape of treatment options in multiple myeloma (MM), indirect and mixed treatment comparisons (ITCs/MTCs) must be conducted to derive relative treatment effects against all relevant comparators in National Institute for Health and Care Excellence (NICE) submissions. The objective was to assess how ITCs and MTCs have been utilised in NICE MM submissions and how they have been perceived by the Evidence Review Groups (ERGs). METHODS: All TAs in MM published by NICE as of 13/04/20 were selected for review. Data was extracted and categorised by method, effect measure, numbers of trials and ERG criticisms. RESULTS: 12 published TAs were identified. All submissions presented ITCs/MTCs except for the earliest one (TA129). Statistical methods used in the base case were: fixed effects synthesis (n=5); match-adjusted indirect treatment comparisons (MAICs) (n=2), MAICs and regression with patient-level data (n=2); random effects synthesis (n=1) and a crude ITC (n=1). Most analyses produced constant hazard ratios (n=9) with the remainder being time-varying hazards (n=2). Number of trials in each network increased from a mean of 3.5 (3-4) in 2007-2013 across 2 submissions to 4.3 (2-7) in 2014-2020 across 9 submissions. Key ERG criticisms included: heterogeneity across studies, especially differences in line of therapy (n=4); sparse network (n=3); similarity/transitivity assumption not assessed or held (n=3); criticisms regarding choice of characteristics adjusted for in the MAIC (n=3); residual bias not assessed in the MAIC (n=2); unclear presentation of ITC/MTC and code used missing from submission (n=2). CONCLUSIONS: This review suggests the utilisation and complexity of ITCs/MTCs has increased over recent years. Whilst additional uncertainty in clinical and cost-effectiveness estimates is expected in the absence of direct evidence, key ERG criticisms show that companies must ensure care is taken to fully understand and follow NICE TSDs to conduct and report ITC/MTC results appropriately.