Phase 3 Randomized Study of Daratumumab (DARA) + Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Alone in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma or for Whom Transplant Is Not Planned As Initial Therapy: Analysis of Minimal Residual Disease in the Cepheus Trial

作者：Sonja Zweegman, Thierry Façon, Vânia Hungria, Nizar J. Bahlis, Christopher P. Venner, Marc Braunstein, Luděk Pour, Josep Marti Tutusaus, Supratik Basu, Yaël C. Cohen, Morio Matsumoto, Kenshi Suzuki, Cyrille Hulin, Sebastian Grosicki, Wojciech Legieć, Meral Beksaç, Ângelo Maiolino, Hiroyuki Takamatsu, Aurore Perrot, Mehmet Turgut, Weiping Liu, Jianping Wang, Katherine Chastain, Jessica Vermeulen, Maria Krevvata, Lorena Lopez-Masi, Jodi Carey, Melissa Rowe, Robin Carson, Saad Z. Usmani · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-200871 · 被引用次数：12 · 研究领域：Multiple Myeloma Research and Treatments、Quinazolinone synthesis and applications、Chronic Lymphocytic Leukemia Research

Introduction: The achievement of minimal residual disease (MRD) negativity is associated with longer-term survival outcomes and has evolved into a strong prognostic clinical endpoint in MM. In the phase 3 CEPHEUS study, DARA in combination with VRd (D-VRd) significantly increased depth of response, including rates of overall MRD negativity, complete response or better (≥CR), and sustained MRD negativity (versus VRd) in patients with transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) or for whom transplant was not intended as initial therapy (transplant deferred). These deep responses translated into a significantly superior progression-free survival (PFS) for D-VRd versus VRd (HR, 0.57; 95% CI, 0.41-0.79; P=0.0005). Here we report an expanded analysis of MRD outcomes from the CEPHEUS study. Methods: CEPHEUS is a multicenter, open-label, randomized, phase 3 study that included eligible patients with NDMM with no intent for transplant based upon age (≥70 yrs), the presence of comorbid conditions likely to hinder transplant or high-dose chemotherapy tolerance, or had deferred first-line transplant. Patients were stratified by International Staging System disease stage and age/transplant eligibility (<70 yrs ineligible, <70 yrs and transplant deferred, ≥70 yrs) and randomized 1:1 to D-VRd or VRd. All patients received eight 21-day cycles of VRd (V: 1.3 mg/m2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-14; d: 20 mg PO/IV Days 1, 2, 4, 5, 8, 9, 11, 12), f...