Subcutaneous daratumumab (Dara) + bortezomib/lenalidomide/dexamethasone (VRd) with Dara + lenalidomide (DR) maintenance in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM): Analysis of sustained minimal residual disease negativity in the phase 3 PERSEUS trial.

7501 Background: Minimal residual disease (MRD) negativity (neg) and sustained MRD neg are associated with longer survival and are strong prognostic clinical endpoints. PERSEUS (NCT03710603) evaluated subcutaneous Dara + VRd induction/consolidation (ind/consol) + DR maintenance (maint) vs VRd ind/consol + R maint in TE NDMM. DVRd significantly improved PFS, complete response or better rate (≥CR), and MRD neg rate. Nearly two-thirds of patients (pts) on DR maint could stop treatment (tx) after achieving sustained remission, leading to DVRd being recommended by NCCN as a preferred TE NDMM regimen. Here, we report the impact of sustained MRD neg status on PFS inPERSEUS. Methods: TE pts with NDMM age 18–70 years (y) were randomized 1:1 to DVRd (DVRd ind/consol + DR maint) or VRd (VRd ind/consol + R maint). The primary endpoint was PFS; MRD neg rate (MRD neg 10 -5 and ≥CR) was a key secondary endpoint. Sustained MRD neg, assessed in the intent-to-treat population, was defined as confirmed MRD neg ≥12 months (mo) apart and without MRD positivity in between. Functionally high risk (FHR) was defined as disease progression ≤18 mo from tx initiation, excluding pre-progression deaths. Results: A total of 709 pts were assigned to DVRd (n=355) or VRd (n=354). At 47.5-mo median follow-up, ≥12-mo sustained MRD neg rates were higher overall with DVRd (64.8%; n=230) vs VRd (29.7%; n=105), and across clinically relevant subgroups, including age ≥65 y and high-risk cytogenetics. Similarly, ≥24-mo sustained MRD neg rates were higher with DVRd (55.8%; n=198) vs VRd (22.6%; n=80). Pts with ≥12-mo sustained MRD neg vs those without had improved 48-mo PFS rates regardless of tx arm (Table). DVRd vs VRd reduced FHR rates (3.1% vs 6.8%), and rates of FHR or pre-progression deaths were lower with DVRd vs VRd (5.4% vs 11.0%) in the first 18 mo. Conclusions: In TE NDMM, nearly two-thirds of pts treated with DVRd induction and DR maint achieved ≥12-mo sustained MRD neg, associated with >95% 48-mo PFS rate. Moreover, ≥24-mo sustained MRD neg rates with DVRd were 2.5 times as high as VRd, and FHR incidence was halved with DVRd vs VRd. Collectively, these data further support the PERSEUS regimen as standard of care for TE NDMM. Clinical trial information: NCT03710603 . Achieved sustained (≥12 mo) MRD neg (10 -5 ) Without achieving sustained (≥12 mo)MRD neg (10 -5 ) DVRd (n=230) VRd(n=105) DVRd (n=125) VRd(n=249) Median PFS, mo (95% CI) NE(NE–NE) NE (NE–NE) HR=0.83(95% CI 0.3–2.3) P =0.7149 NE (47.9–NE) NE (45.3–NE) HR=0.80(95% CI 0.6–1.2) P =0.2489 48-mo PFSrate, % (95% CI) 95.3 (91.4–97.5) 94.2 (87.6–97.4) 60.3 (48.0–70.5) 54.9 (47.7–61.4) Hazard ratio, HR; NE, not estimable. Median PFS and 95% CI are from Kaplan-Meier estimates. P -value is from unstratified log-rank test.