Sustained Minimal Residual Disease Negativity With Daratumumab in Newly Diagnosed Multiple Myeloma: MAIA and ALCYONE
Jesus F San-Miguel 1 , Hervé Avet-Loiseau 2 , Bruno Paiva 3 , Shaji K Kumar 4 , Meletios A A Dimopoulos 5 , Thierry Facon 6 , Maria-Victoria Mateos 7 , Cyrille Touzeau 8 , Andrzej J Jakubowiak 9 , Saad Z Usmani 10 , Gordon Cook 11 , Michele Cavo 12 , Hang Quach 13 , Jon Ukropec 14 , Priya Ramaswami 15 , Huiling Pei 16 , Mia Qi 17 , Steven Sun 18 , Jianping Wang 19 , Maria Krevvata 20 , Nikki DeAngelis 20 , Christoph Heuck 20 , Rian Van Rampelbergh 21 , Anupa Kudva 17 , Rachel Kobos 18 , Ming Qi 22 , Nizar J Bahlis 23
In patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab reduced the risk of disease progression or death by 44% in MAIA (daratumumab/lenalidomide/dexamethasone; D-Rd) and 58% in ALCYONE (daratumumab/bortezomib/melphalan/prednisone; D-VMP).
Minimal residual disease (MRD) is a sensitive measure of disease and response to therapy. MRD-negativity status and durability were assessed in MAIA and ALCYONE. MRD assessments using next-generation sequencing (10-5) occurred for patients achieving complete response (CR) or better, and after ≥CR at 12, 18, 24, and 30 months from the first dose.
Progression-free survival (PFS) by MRD status and sustained MRD negativity lasting ≥6 and ≥12 months were analyzed in the intent-to-treat population and among patients achieving ≥CR. In MAIA, (D-Rd, n=368; Rd, n=369), and ALCYONE (D-VMP, n=350; VMP, n=356), the median duration of follow-up was 36.4 months and 40.1 months, respectively. MRD-negative status and sustained MRD negativity lasting ≥6 and ≥12 months were associated with improved PFS, regardless of treatment group. However, daratumumab-based therapy improved rates of MRD negativity lasting ≥6 months (D-Rd, 14.9% vs Rd, 4.3%; D-VMP, 15.7% vs VMP, 4.5%) and ≥12 months (D-Rd, 10.9% vs Rd, 2.4%; D-VMP, 14.0% vs VMP, 2.8%), both of which translated to improved PFS versus control groups.
In a pooled analysis, patients who were MRD negative had improved PFS versus patients who were MRD positive. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes. ClinicalTrials.gov identifier NCT02252172 (MAIA); NCT02195479 (ALCYONE).