Saad Z Usmani, Thierry Facon, Vania Hungria, Nizar J Bahlis, Christopher P Venner, Marc Braunstein, Ludek Pour, Josep M Marti, Supratik Basu, Yael C Cohen, Morio Matsumoto, Kenshi Suzuki, Cyrille Hulin, Sebastian Grosicki, Wojciech Legiec, Meral Beksac, Angelo Maiolino, Hiroyuki Takamatsu, Aurore Perrot, Mehmet Turgut, Weiping Liu, Jianping Wang, Maria Krevvata, Jaclyn Stanziola, Matteo Loi, Emilie M J Van Brummelen, Lorena Lopez-Masi, Melissa Rowe, Robin L Carson, Sonja Zweegman
The phase III CEPHEUS trial (ClinicalTrials.gov identifier: NCT03652064) of patients with transplant-ineligible (TIE) or transplant-deferred newly diagnosed multiple myeloma (NDMM; N = 395) demonstrated improved overall minimal residual disease (MRD) negativity rates among patients achieving ≥complete response and progression-free survival (PFS) with daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) versus VRd. We present efficacy and safety outcomes in the CEPHEUS TIE subgroup (N = 289; DVRd, n = 144; VRd, n = 145). Patients were either age 18-70 years with ≥1 comorbidity likely to negatively affect tolerability of high-dose chemotherapy with autologous stem cell transplantation or age ≥70 years. At a median follow-up of 58.7 months, the MRD negativity rate (10-5) was 60.4% (DVRd) versus 39.3% (VRd; P = .0004). Rates of sustained MRD negativity (10-5) for ≥12 months (47.2% v 28.3%; P = .0010) and ≥24 months (40.3% v 22.8%; P = .0015) were significantly higher with DVRd. Risk of disease progression or death was 49% lower for DVRd versus VRd (hazard ratio [HR], 0.51 [95% CI, 0.35 to 0.74]; P = .0003). Although immature, overall survival favored DVRd (HR, 0.66 [95% CI, 0.42 to 1.03]). Adverse events were consistent with known safety profiles. This analysis demonstrates that the deep responses achieved with DVRd translate into improved PFS in patients with TIE NDMM, reinforcing DVRd as a standard of care.