Daratumumab in Combination with Carfilzomib, Lenalidomide, and Dex (KRd) in Pts with NDMM
Description: Daratumumab (DARA) in Combination with Carfilzomib, Lenalidomide, and Dexamethasone (KRd) in Patients with Newly Diagnosed Multiple Myeloma (MMY1001): Updated Results from an Open-Label, Phase 1b Study
Ajai Chari, MD
Mt. Sinai School of Medicine
New York, NY, USA
Introduction: Standard of care treatments for patients (pts) with newly diagnosed multiple myeloma (NDMM) include triplet regimens containing a proteasome inhibitor (PI) or an immunomodulatory drug (IMiD), with or without autologous stem cell transplant (ASCT). Among triplets, extended treatment with KRd has emerged as a highly active combination in NDMM (Jakubowiak AJ, et al. Blood, 2012;120:1801-1809). As multiple myeloma progresses, the depth and duration of clinical response is reduced with each treatment relapse, making it critical for front-line therapy to drive pts to deep and sustained clinical responses. Daratumumab (DARA) is a human IgGκ monoclonal antibody (mAb) targeting CD38 with direct on-tumor and immunomodulatory mechanisms of action. DARA induces rapid, deep, and durable responses in combination with dexamethasone and either bortezomib or an IMiD (lenalidomide or pomalidomide) in pts with relapsed/refractory MM (RRMM; Palumbo A, et al. NEJM. 2016 375:754-766; Dimopoulos MA, et al. NEJM. 2016 375:1319-1331; Chari A, et al. Blood. 2017; epub, ahead of print). This open-label, multicenter, phase 1b study investigated the safety profile and efficacy of DARA in combination with KRd in NDMM.
Conclusion: DARA+KRd, with weekly K dosing, is well tolerated in pts with NDMM and demonstrates a safety profile consistent with previous reports of DARA and KRd. High response rates were observed with DARA+KRd and the depth of response improved with treatment duration. No adverse impact on stem cell collection was observed. These data support further investigation of DARA+KRd in NDMM.
Authors: Ajai Chari, Saad Z Usmani, MD, Amrita Krishnan, MD, Sagar Lonial, MD, Raymond Comenzo, Kaida Wu, Jianping Wang, Parul Doshi, Brendan M Weiss, MD, Jordan Schecter and Andrzej J. Jakubowiak, MD