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8011 Background: In the primary analysis of the phase 2 randomized GRIFFIN study, DARA + RVd (D-RVd) improved the stringent complete response (sCR) rate by end of consolidation for transplant-eligible NDMM (42.4% vs 32.0%; 1-sided P = 0.068). With longer follow-up (median, 38.6 mo), D-RVd vs RVd improved MRD-negativity (10–5) rates in clinically relevant subgroups (ISS stage III, 71% vs 36%; high cytogenetic risk, 44% vs 29% [del17p, t(4;14), or t(14;16)]; revised high cytogenetic risk, 55% vs 32% [del17p, t(4;14), t(14;16), t(14;20), or gain 1q]). Here we present a post hoc analysis of sustained MRD negativity (median follow-up, 38.6 mo) in the same subgroups and in patients (pts) with ≥CR. Methods: Transplant-eligible NDMM pts were randomized 1:1 to 4 D-RVd/RVd induction cycles, ASCT, 2 D-RVd/RVd consolidation cycles, and 2 years of maintenance therapy with lenalidomide (R) ± DARA. For induction/consolidation (21-day cycles), pts received R (25 mg PO Days [D] 1-14), V (1.3 mg/m2 SC D1, 4, 8, 11), and d (40 mg PO weekly) ± DARA (16 mg/kg IV D1, 8, 15 of Cycles 1-4 and D1 of Cycles 5-6). In maintenance (28-day cycles), pts received R (10 mg PO D1-21; if tolerated, 15 mg in Cycles 10+) ± DARA (16 mg/kg IV Q8W/Q4W or 1800 mg SC per protocol amendments). The primary endpoint was sCR rate by end of consolidation. Results: The following features were balanced among randomized pts (D-RVd, n = 104; RVd, n = 103): high cytogenetic risk (16; 14), revised high cytogenetic risk (42; 37), gain 1q (34; 28), and ISS stage III (14; 14). Sustained MRD-negativity rates at 10–5 lasting ≥6 and ≥12 months were higher for D-RVd vs RVd among all high-risk subgroups (Table). D-RVd was superior to RVd for rates of sustained MRD negativity lasting ≥12 months for pts with ≥CR (53.7% vs 20.3%) and sCR (59.1% vs 17.4%; Table). Among all pts with sustained MRD negativity, only 1 D-RVd pt subsequently had disease progression, and 1 RVd pt died. Additional data on MRD at 10–6 and PFS will be presented. Conclusions: MRD data in GRIFFIN show that the addition of DARA to RVd induction/consolidation and R maintenance may lead to durable MRD-negativity (10–5) rates in pts with transplant-eligible NDMM with high cytogenetic risk, ISS stage III, and those who achieve ≥CR or sCR, however larger studies are needed. Clinical trial information: NCT02874742. [Table: see text]