OBJECTIVES: Chemotherapy (CT), targeted therapy (TT), and immunotherapy (IT), which are commonly used to treat MM, are often associated with adverse effects (AEs). This study estimated the per-event cost and economic burden associated with managing the most common and/or severe AEs for these 3 treatment categories from the UK National Health Service perspective.  METHODS: A literature review evaluated the incidence and types of AEs associated with the 3 treatment categories. A total of 29 AEs (CT:11; TT:11; and IT:7), all-severity grades (Gr) occurring in >20% or Gr 3/4 occurring in >5%, were selected. Medical resource use related to the management of AEs was assessed by conducting 2 blinded Delphi panel cycles with 4 clinicians. Published unit costs were used to estimate the costs per AE and then combined with AE incidence (assuming 1 occurrence/patient/cycle), treatment usage, and 1-year prevalence of MM (2027 cases) to estimate treatment burden in the UK for a single AE occurrence. RESULTS: For CT, the most cost-intensive AEs were Gr 3/4 peripheral neuropathy and thrombocytopenia, representing a mean cost per event per patient of £432 and £277, respectively. For TT, they were Gr 3/4 squamous cell carcinoma (SCC) and Gr 1/2 skin papilloma, with a mean cost of £1281 and £845, respectively. For IT, they were Gr 3/4 diarrhea and colitis, both with a mean cost of £2836. The top 5 AEs with the highest treatment burden across all 3 categories included Gr 3/4 SCC (mean total cost of £202,493), Gr 3/4 diarrhea (£132,032), Gr 1/2 skin papilloma (£125,995), Gr 3/4 colitis (£124,695) and Gr 3/4 immune-related hypophysitis (£98,393), and Gr 1/2 hyperkeratosis (£70,292).  CONCLUSIONS: In the UK, costs for management of AEs associated with MM therapies can be substantial. The total burden may be underestimated since it does not account for AE recurrence.