OBJECTIVES:  We assessed treatment costs for MM patients by line of therapy (LOT), service category, and time since treatment initiation. METHODS:  This was a retrospective observational study using the MarketScan database. Patients were adults with MM (ICD-9-CM code 203.0x) who initiated MM treatment between Jan 1, ‘06 and Dec 31, ‘14. LOT was defined by receipt of new MM treatment or a gap > 90 days in MM treatment. Patients with prior SCT or insufficient continuous enrollment to determine LOT were excluded. Mean monthly healthcare costs were calculated by LOT, stratified by on- and off-treatment periods, service category, and time since treatment initiation. LOT and on/off treatment period mean costs were weighted by duration. RESULTS:  9,464 patients met study criteria (mean age 67 years, 57% male). Mean costs during the 6 months before 1L were $6,075/month. Mean total monthly costs ranged from $9,664 to $11,760 across the 4 LOTs. On-treatment costs per month were nearly twice the off-treatment costs in all lines. MM medications represented 36%-45% of total costs across LOTs. MM complications and Tx-related AEs represented 26%-32% of total costs across LOTs. Total costs per month were highest at treatment initiation in all LOTs (1L: $17,234; 2L: $15,741; 3L: 15,223; 4L:16,211). Costs declined over time in each LOT. CONCLUSIONS: MM medications and treatment of MM complications/AEs represented the majority of healthcare costs in MM patients who did not undergo an SCT. Monthly total costs at treatment initiation were greatest for 1L. In each LOT monthly costs declined over time. Therapies that extend PFS and the treatment-free interval likely reduce the costs of MM treatment and defer costs of subsequent MM treatment.