Background: MM is the most common blood cancer among African Americans (AA). The study aimed to compare clinical and economic outcomes for AA with newly diagnosed MM who received novel vs non-novel agents as first-line (1L) Tx for MM. Methods: Pts with MM in SEER-Medicare (2007-2014) were included. Continuous Medicare enrollment for 6 mos before (baseline) and after 1L initiation date (index date) was required, unless pts died. Novel agent (eg, bortezomib [V], lenalidomide [R]) and non-novel agent users were identified based on the 1L Tx pts received. Overall survival (OS), myeloma specific survival (MSS), and healthcare costs were compared between AA novel and non-novel users. Among AA novel users, outcomes were further compared between 1L R + steroid (Rd) vs V + steroid (Vd) users. Results: Among 657 included AA pts, 398 (61%) used 1L novel agents. This proportion was significantly lower compared with caucasian (66%, p = 0.02). AA novel users were significantly younger (mean: 70 vs 73 yrs, p < 0.001). Both median OS (3.1 vs 1.8 yrs, p < 0.001) and MSS (not reached vs 57.7 mos, p < 0.01) were significantly longer for AA novel users than non-novel users; after adjusting for baseline characteristics, the risk of all-cause death remained lower for AA novel users (adj hazard ratio [HR] = 0.77, p = 0.01). AA non-novel users had numerically higher monthly medical costs than AA novel users (adj mean difference: $951), which were driven by higher inpatient ($2,571) and emergency room ($38) costs (both p < 0.05). Total costs (medical + pharmacy) were comparable between the two AA cohorts. Among AA novel users, 102 (26%) and 147 (37%) used 1L Rd and Vd, respectively. Time on Tx (DOT) was longer for Rd vs Vd (median 4.6 vs 4.0 mos, adj HR = 0.72, p = 0.04). A trend of longer time to next line Tx (TTNT) initiation or death (a proxy of PFS) was observed among Rd users (median 17.6 vs. 12.1 mos, p = 0.06). Conclusions: AA pts with MM who received 1L novel agents had longer OS and MSS compared with those who did not. Among novel users, pts receiving Rd had longer DOT and trended toward longer TTNT, compared with Vd. Results suggest that increasing the novel agents use, particularly Rd, may improve outcomes among AA pts with MM.