Introduction: The therapeutic landscape in relapsed/refractory multiple myeloma (RRMM) has changed rapidly, with twenty-two drug approvals since 2012. We characterized population-level trends in RRMM therapy selection, survival and cost outcomes associated with RRMM treatment over time. Materials and Methods: Our cohort included adults diagnosed with multiple myeloma (MM) in the SEER-Medicare database from 2007 – 2017 who received at least one antimyeloma agent. MM-directed therapies and lines of therapy were identified. Changes in 2LT regimens over time were described. Trends in overall survival from 2LT initiation over time were analyzed using a Cox proportional hazards model adjusting for factors associated with survival in MM. Trends in mean inflation-adjusted cost per 12 months of 2LT were analyzed using JoinPoint analysis. Results: 9,822 patients met eligibility criteria, of whom 5,866 (59.7%) received 2LT. By 2018, 46% of 2LT regimens contained at least one agent approved in 2012 or later. Year of 2LT initiation was associated with improved overall survival (HR 0.78 per 5 years, 95% CI 0.74-0.84) after adjustment. Costs associated with 2LT increased over the study period, and the rate of cost increase increased significantly after 2012 (0.89%/year v 9.9%/year, p<0.001), with higher total costs for regimens containing newer novel agents (mean $224,193 v. $189,381, P < .001) Conclusion: Overall survival after initiation of 2LT has improved, however this has been accompanied by significant increases in costs of RRMM treatment, particularly for patients receiving newer novel agents. These findings provide useful context for existing and future drug approvals in RRMM. MICROABSTRACT: Novel therapeutics have changed the landscape for managing relapsed multiple myeloma. We explore population level trends in second line multiple myeloma therapy selection, survival, and cost. Attrition after first-line therapy is high and many patients never receive second-line therapy. For patients receiving second line therapy, we found increased adoption of novel agents, improving survival, and increasing costs over time.