e18839 Background: Despite advances in the treatment of MM, prognosis remains poor for most patients due to its refractory nature. In a phase 3 study, a once-per-week regimen of XVd showed a novel, effective, and convenient option for patients with previously treated MM. This study was conducted to estimate the projected budget impact (BI) of XVd in patients with previously treated MM from the perspective of a third-party payer and Medicare in the US. Methods: The introduction of XVd as a treatment option for patients with previously treated MM compared to the status quo (i.e. without the introduction of XVd) was considered from a private third-party US payer and a Medicare perspective in one-year increments for the first 3 years. The model assumed market uptake of 5.9%, 7.2%, and 7.7% at years 1, 2 and 3, respectively. Total annual treatment costs (2020 US dollars [USD]) were calculated as the sum of drug costs, the costs of treating serious treatment emergent adverse events (grade ≥3), ongoing best supportive care costs, and mortality costs. Results: In the base-case analysis for a private third-party payer plan (1,000,000 members), 3 to 4 patients were projected to receive XVd out of 47 to 49 eligible patients each year. The absolute BI (Millions, USD) of including XVd from a private third-party payer plan perspective was $0.06, $0.07, $0.08 and $0.22 for years 1, 2, 3, and overall, respectively. The relative BI of including XVd was 0.33%, 0.40%, 0.43%, and 0.38% for years 1, 2, 3, and overall, respectively. This translated to a per member per month (PMPM) budget impact of $0.005, $0.006, $0.007, and $0.006 (USD), for years 1, 2, 3, and overall, respectively. In the base-case analysis from the Medicare perspective (59,499,015 members), 1,361 to 1,808 patients were projected to receive XVd out of 22,892 to 23,425 eligible patients each year. From a Medicare perspective, the absolute BI (Millions, USD) of including XVd was $29.68, $36.62, $39.42 and $105.72 for years 1, 2, 3, and overall, respectively. The relative BI of including XVd was 0.33%, 0.40%, 0.43%, and 0.38% percent for years 1, 2, 3, and overall, respectively. This translated to a PMPM budget impact of $0.041, $0.051, $0.054, and $0.049 (USD), for years 1, 2, 3, and overall, respectively. One-way sensitivity analyses showed general consistency with the base-case findings. Conclusions: Understanding the potential BI of new therapies in MM is vital for decision makers to manage spending and assess the value of treatments. The introduction of XVd presents a small and manageable BI for a third-party US payer and Medicare.