Daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) in patients (pts) with newly diagnosed multiple myeloma (NDMM): Final analysis of transplant-ineligible (TIE) pts in the phase 3 CEPHEUS study.

7513 Background: The phase 3 CEPHEUS study established that DVRd improved overall minimal residual disease (MRD)-negativity (neg) rates and progression-free survival (PFS) vs VRd in pts with TIE or transplant-deferred (TD) NDMM. The first analysis of the DVRd TIE subpopulation at a median follow-up of 58.7 months (mo) showed a complete response or better (≥CR) rate of 80.6% and overall MRD neg rate of 60.4%, with ~70% of pts alive and progression free. This final analysis of the CEPHEUS TIE subpopulation describes a longer median follow-up of 76.0 mo. Methods: The primary endpoint of overall MRD neg rate (10 -5 and ≥CR), and secondary endpoints, including investigator-assessed PFS and ≥CR rate, and sustained MRD neg (confirmed MRD neg ≥12 months +/- 1 mo apart without MRD positivity in between and ≥CR) were assessed in the TIE population. The study was closed at the final analysis and pts were able to continue their study treatment via post-study access. Results: Of 395 pts enrolled, 289 pts with TIE NDMM received either DVRd (n=144) or VRd (n=145). The overall MRD neg rate at 10 -5 was 61.1% for DVRd and 40.0% for VRd (odds ratio OR 2.35; 95% CI 1.47–3.77; P =0.0004) and at 10 -6 was 46.5% for DVRd vs 27.6% for VRd (OR 2.27; 95% CI 1.39–3.71; P =0.0010). Sustained MRD neg rate at 10 -5 was 49.3% for DVRd and 29.0% for VRd (OR 2.40; 95% CI 1.47–3.91; P =0.0005) and at 10 -6 was 37.5% for DVRd and 16.6% for VRd (OR 3.01; 95% CI 1.73–5.24; P <0.0001). Overall ≥CR rate was 80.6% for DVRd and 61.4% for VRd (OR 2.64; 95% CI 1.54–4.51; P =0.0003). Median investigator-assessed PFS was not estimable (NE; 95% CI 74.81–NE) for DVRd and was 50.20 mo (95% CI 41.95–62.95) for VRd (HR 0.55; 95% CI 0.39–0.78; P =0.0007), with 59.3% for DVRd vs 38.3% for VRd alive and progression free at 72 mo. OS favored DVRd over VRd (HR 0.84; 95% CI 0.57–1.24), particularly when censoring for COVID-19, which significantly impacted this study (HR 0.74; 95% CI 0.49–1.12). The treatment effect was consistent across most subgroups (Table). Conclusions: After median follow-up of over 6 years, the final analysis of the CEPHEUS trial demonstrated that TIE pts treated with DVRd continue to have deep and durable responses compared with those on VRd, which is crucial for patients for whom transplant is not an option. These data continue to reinforce DVRd as a standard of care in the TIE NDMM population. Clinical trial information: NCT03652064 . MRD neg (10 -5 ) rate, % Median PFS, mo BL characteristic DVRd VRd OR 95% CI DVRd VRd HR 95% CI ISS stage I 66.0 41.7 2.72 1.30–7.11 NE 60.5 0.52 0.28–0.97 II 59.3 45.6 1.73 0.82–3.68 NE 49.4 0.50 0.28–0.88 III 57.5 30.0 3.16 1.26–7.94 66.4 43.8 0.66 0.35–1.24 Cytogenetic risk High 50.0 50.0 1.00 0.28–3.57 58.0 31.7 0.82 0.36–1.87 Standard 63.8 39.6 2.68 <jats:td colspan="1" rowspan="