Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.
Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Expert Opin Biol Ther. 2024 May;24(5):365-381. doi: 10.1080/14712598.2024.2357382. Epub 2024 May 19.
Gain/amplification of 1q (+1q) represents one of the most prevalent cytogenetic abnormalities (CAs) observed in multiple myeloma (MM). Historical studies predating the advent of anti-CD38 monoclonal antibodies (moAbs) implicated + 1q in poor prognoses, prompting its integration into novel staging systems. However, with the emergence of daratumumab and isatuximab, two pivotal anti-CD38 moAbs, the landscape of MM therapy has undergone a profound transformation.
This review encompasses a comprehensive analysis of diverse study methodologies, including observational investigations, clinical trials, meta-analyses, and real-world database analyses. By synthesizing these data sources, we aim to provide an overview of the current understanding of + 1q in the context of anti-CD38 moAbs therapies.
Despite the paucity of available data, evidence suggests a potential mitigating effect of daratumumab on the adverse prognostic implications of + 1q. However, this benefit seems to diminish in patients harboring ≥ 4 copies or with concurrent high-risk CAs. On the other hand, isatuximab demonstrated promising outcomes in the relapsed-refractory setting for + 1q MM patients. Nevertheless, direct comparison between the two compounds is currently challenging. The current evidence firmly supports the integration of anti-CD38 moAb-based therapies as the standard of care for + 1q patients, pending further elucidation.
1q 增益/扩增(+1q)是多发性骨髓瘤(MM)中最常见的细胞遗传学异常(CAs)之一。在抗 CD38 单克隆抗体(moAb)出现之前的历史研究表明,+1q 与预后不良有关,这促使其被纳入新的分期系统。然而,随着达雷妥尤单抗和伊沙妥昔单抗这两种关键的抗 CD38 moAb 的出现,MM 治疗领域发生了深刻的变革。
本综述涵盖了各种研究方法的全面分析,包括观察性研究、临床试验、荟萃分析和真实世界数据库分析。通过综合这些数据源,我们旨在提供当前对抗 CD38 moAb 治疗中+1q 的理解概述。
尽管可用数据有限,但有证据表明达雷妥尤单抗可能减轻+1q 的不良预后影响。然而,这种益处似乎在携带≥4 个拷贝或同时存在高风险 CA 的患者中减弱。另一方面,伊沙妥昔单抗在复发性/难治性 MM 患者中显示出在+1q 患者中的有前景的结果。然而,目前还难以直接比较这两种药物。目前的证据强烈支持将基于抗 CD38 moAb 的治疗作为+1q 患者的标准治疗,等待进一步阐明。