Lonial Sagar, Dimopoulos Meletios A, Berdeja Jesus G, Richardson Paul G, Quach Hang, Rodríguez-Otero Paula, Maciag Paulo, Hong Kevin, Amatangelo Michael, Chen Min, van de Donk Niels W C J
Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Future Oncol. 2025 Jun;21(14):1761-1769. doi: 10.1080/14796694.2025.2501920. Epub 2025 May 10.
Multiple myeloma (MM) is a plasma cell neoplasm that stems from the malignant transformation of clonal plasma cells. It is characterized by multiple periods of remission and relapse requiring multiple lines of therapy, with response to treatment and survival decreasing with each successive relapse. To achieve deep and durable responses in relapsed/refractory MM (RRMM), novel treatments are required. Iberdomide (IBER), an oral CELMoD™ agent, is associated with greater tumoricidal and immune-stimulatory effects than immunomodulatory drugs (IMiDs®). IBER has been shown to have synergy with dexamethasone (DEX) and daratumumab (DARA) in vitro. In a phase I/II trial, IBER in combination with DARA and DEX (IberDd) was well tolerated and demonstrated promising preliminary efficacy in patients with heavily pretreated RRMM, including patients refractory to IMiD agents, DARA, and proteasome inhibitors. EXCALIBER-RRMM is a unique confirmatory phase III trial that incorporates a 2-stage seamless design to firstly address dose optimization of IberDd, and secondly, to compare the efficacy and safety of the selected IberDd dose with DARA, bortezomib, and DEX in patients with early-line (1 or 2 prior lines of therapy) RRMM. www.clinicaltrials.gov identifier is NCT04975997.
多发性骨髓瘤（MM）是一种浆细胞肿瘤，起源于克隆性浆细胞的恶性转化。其特点是有多个缓解期和复发期，需要多线治疗，且每次复发后治疗反应和生存率都会降低。为了在复发/难治性MM（RRMM）中实现深度和持久的反应，需要新的治疗方法。泊马度胺（IBER）是一种口服的CELMoD™药物，与免疫调节药物（IMiDs®）相比，具有更强的杀肿瘤和免疫刺激作用。体外研究表明，IBER与地塞米松（DEX）和达雷妥尤单抗（DARA）具有协同作用。在一项I/II期试验中，IBER联合DARA和DEX（IberDd）耐受性良好，在经过大量预处理的RRMM患者中显示出有前景的初步疗效，包括对IMiD药物、DARA和蛋白酶体抑制剂耐药的患者。EXCALIBER-RRMM是一项独特的验证性III期试验，采用两阶段无缝设计，首先确定IberDd的剂量优化，其次，在一线（1或2线既往治疗）RRMM患者中比较所选IberDd剂量与DARA、硼替佐米和DEX的疗效和安全性。www.clinicaltrials.gov标识符为NCT04975997。
