Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled trial

作者：Dimopoulos MA, Schjesvold F, Fu C, Hartley-Brown MA, Gomez C, Reece D, Mikala G, Alkharabsheh O, Parrish C, de Queiroz Crusoé E, Gálvez K, Idrobo H, White D, Gupta R, Lee C, Liu CJ, Quach H, Wang Y, Cerchione C, Forsyth C, Hungria V, Kalaskar P, Graklanov V, Ho PJ, Klaiber-Hakimi M, Kwong YL, Louzada M, Mazumder A, Miles O, Nagarajan C, Prasad SVSS, Raab MS, Varga G, von der Heyde E, Xia Z, Ochoa PA, Oriol A, Yuda J, Kuroda J, Gong J, Zhou Z, Maciag P, Yu B, Rocci A, Koo P, Katz J, Richardson PG, SUCCESSOR-2 Trial Investigators · 发表于：Lancet (London, England) · 年份：2026 · DOI：10.1016/S0140-6736(26)01088-3 · 研究领域：Antineoplastic Combined Chemotherapy Protocols、Dexamethasone、Multiple Myeloma、Oligopeptides、Aged、Female、Humans、Male、Middle Aged

BACKGROUND: A growing number of patients with multiple myeloma are anti-CD38 antibody-exposed and lenalidomide-exposed at first relapse, subsequently limiting their treatment options. Mezigdomide, a potent cereblon E3 ligase modulator, induces maximal, rapid Ikaros and Aiolos degradation, resulting in enhanced myeloma cell cytotoxicity and immune stimulation versus immunomodulatory drugs. The SUCCESSOR-2 trial evaluates the efficacy and safety of mezigdomide in combination with carfilzomib and dexamethasone versus carfilzomib plus dexamethasone. METHODS: This phase 3, open-label, randomised controlled trial was conducted at 160 hospital-based sites in 26 countries using a two-stage, inferentially seamless design. Eligible adult patients had measurable multiple myeloma, had received at least one previous regimen (including anti-CD38 antibodies and lenalidomide) on which they had achieved minimal response or better, and documented disease progression during or after their most recent treatment. Interactive response technology was used to randomly assign patients, stratified by age (≤70 years or >70 years), number of previous lines of therapy (≤2 or >2), and International Staging System stage (I, II, or III). Patients received oral mezigdomide (days 1-21 of each 28-day cycle) plus intravenous carfilzomib (56 mg/m2 weekly) and oral or intravenous dexamethasone (40 mg weekly) or carfilzomib (56 mg/m2 twice weekly or 70 mg/m2 weekly) and dexamethasone (20 mg twice weekly or 40 mg ...