Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE

• Published in: Blood Vol. 139; no. 4; pp. 492 - 501
• Main Authors: San-Miguel, Jesus, Avet-Loiseau, Hervé, Paiva, Bruno, Kumar, Shaji, Dimopoulos, Meletios A., Facon, Thierry, Mateos, María-Victoria, Touzeau, Cyrille, Jakubowiak, Andrzej, Usmani, Saad Z., Cook, Gordon, Cavo, Michele, Quach, Hang, Ukropec, Jon, Ramaswami, Priya, Pei, Huiling, Qi, Mia, Sun, Steven, Wang, Jianping, Krevvata, Maria, DeAngelis, Nikki, Heuck, Christoph, Van Rampelbergh, Rian, Kudva, Anupa, Kobos, Rachel, Qi, Ming, Bahlis, Nizar J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.01.2022; American Society of Hematology
• Subjects: Aged; Antibodies, Monoclonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Clinical Trials and Observations; Female; Humans; Male; Middle Aged; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Neoplasm, Residual - diagnosis; Neoplasm, Residual - drug therapy; Progression-Free Survival; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2020010439

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 at least 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 at least CR. In MAIA (D-Rd, n = 368; lenalidomide and dexamethasone [Rd], n = 369) and ALCYONE (D-VMP, n = 350; bortezomib/melphalan/prednisone [VMP], n = 356), the median duration of follow-up was 36.4 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 vs control groups. In a pooled analysis, patients who were MRD negative had improved PFS vs patients who were MRD positive. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes. These trials were registered at www.clinicaltrials.gov as #NCT02252172 (MAIA) and #NCT02195479 (ALCYONE). •In patients with transplant-ineligible NDMM, durable MRD negativity is associated with improved PFS.•Daratumumab-based therapies are associated with higher rates and durability of MRD negativity. [Display omitted]