Background: Several studies demonstrate that LEN MNTC post ASCT reduces the risk of disease progression or death in patients (pts) with MM by ≈ 50% (Attal NEJM 2012; McCarthy NEJM 2012; Palumbo NEJM 2014). However, these studies were not powered for OS. To assess the effect of LEN MNTC post ASCT on OS, an MA was conducted. Methods: A prospectively planned MA assessed the OS of LEN vs placebo/no MNTC (control; CTL) after ASCT. A search identified 17 randomized controlled trials (RCTs) using LEN post ASCT. 3 RCTs (IFM 2005-02, CALGB 100104 [Alliance], GIMEMA RV-209) met prespecified inclusion criteria (had pt-level data, a CTL arm, and achieved database lock for primary efficacy analysis of NDMM pts receiving LEN post ASCT). A March 2015 cutoff of the 3 RCTs enabled sufficient OS events to test treatment effect (HR = 0.78). Results: In the 3 RCTs, 1209 pts were randomized from 2005 to 2009 to receive LEN (n = 605) 10 mg/day on days 1-21/28 (GIMEMA) or 1-28/28 (IFM and CALGB) or CTL (n = 604). With a median follow-up of 6.6 yrs, 491 pts (41%) had died. Baseline characteristics were generally balanced in the pooled data. After induction and single (82%) or tandem (18%) ASCT, 55% of pts achieved a complete response (CR) or very good partial response (VGPR). Median OS for LEN vs CTL was not reached vs 86 mos (HR = 0.74; 95% CI, 0.62-0.89; log-rank P = .001), and 5-, 6-, and 7-yr OS were longer in LEN vs CTL group (71% vs 66%, 65% vs 58%, and 62% vs 50%, respectively). Fisher’s combination test confirmed the significant OS benefit of the MA (P = .001). Pts who achieved ≤ PR post ASCT benefited from LEN (HR = 0.86; 95% CI, 0.65-1.15) as well as pts with CR/VGPR (HR = 0.70; 95% CI, 0.54-0.90). OS benefit was generally consistent across subgroups. Heterogeneity test showed significant difference across trials (P = .047). The potential impact of baseline/disease characteristics, as well as 2^nd-line therapy (IFM and CALGB), on OS will be explored and presented. Second primary malignancy data will be presented. Conclusions: This large MA demonstrates that LEN MNTC significantly prolonged OS vs CTL post ASCT, including in pts who achieved CR, demonstrating benefit in pts in all response categories. Clinical trial information: NCT00430365; NCT00114101; NCT00551928