Background: In the US and Europe, lenalidomide (LEN or R) was the first approved drug for post-SCT MT in MM. RVD induction is common in NDMM, but real-world evidence of R-MT after RVD and SCT is limited, particularly in HR pts. Here we report results of a retrospective observational analysis comparing R-MT vs No-MT in this setting. Methods: This analysis used electronic health records from the Flatiron Health database. Eligible pts diagnosed with MM between Jan 2011 and Dec 2017 and ≥ 2 documented clinical visits were included. NDMM was defined as no MM treatment (Tx) > 14 days (d) prior to first diagnosis. Index date was defined as the earlier of SCT date + 90 d or start of R-MT. Pts were identified as HR by FISH at diagnosis using international standards (Table). Time to next Tx (TTNT; duration from the index date to start of a new Tx line) was analyzed by Kaplan-Meier method and Cox proportional hazards model. Results: Among 340 pts who received RVD induction and SCT, 85 pts were HR; 41 (48%) received R-MT and 44 (52%) did not (No-MT). Pts receiving R-MT vs No-MT were older (mean age 62 vs 58 yrs; P = .0285), and a higher proportion had an ECOG performance status of 0 (80% vs 41%; P = .0399). More R-MT pts had chromosome 1 abnormalities, and fewer had del17p13. Median follow-up was 21.9 vs 9.7 mos. A smaller proportion of R-MT pts advanced to second line (2L) Tx (24% vs 59%) and had a significantly longer median TTNT (SCT + 90 d) (38.8 vs 2.8 mos; hazard ratio, 3.5 [95% CI, 2.25-5.58]; P< .001). Conclusions: This analysis demonstrated that HR pts with NDMM receiving R-MT were less likely to progress to 2L and had a significantly longer TTNT. These real-world outcomes align with clinical trial outcomes, which showed improved PFS with R-MT vs placebo or observation in HR pts. While HR pts may benefit from the addition of a proteasome inhibitor to MT, this study shows the benefit of single-agent LEN. Future studies are needed to determine the impact on pt survival and healthcare costs.Table: