Extra copies of chromosome 1q21 (+1q: gain = 3 copies, amp >= 4 copies) are associated with worse outcomes in multiple myeloma (MM). This systematic review assesses the current reporting trends of +1q, the efficacy of existing regimens on +1q, and its prognostic implications in MM randomized controlled trials (RCTs). Pubmed, Embase and Cochrane Registry of RCTs were searched from January 2012 to December 2022. Only MM RCTs were included. A total of 124 RCTs were included, of which 29 (23%) studies reported on +1q. Among them, 10% defined thresholds for +1q, 14% reported survival data separately for gain and amp, and 79% considered +1q a high-risk cytogenetic abnormality. Amongst RCTs that met the primary endpoint showing improvement in progression free survival (PFS), lenalidomide maintenance (Myeloma XI), selinexor (BOSTON), and isatuximab (IKEMA and ICARIA) were shown to improve PFS for patients with evidence of +1q. Some additional RCT’s such as Myeloma XI+ (carfilzomib), ELOQUENT-3 (elotuzumab), and HOVON-65/GMMG-HD4 (bortezomib) met their endpoint showing improvement in PFS and also showed improvement in PFS in the +1q cohort, although the confidence interval crossed 1. All six studies that reported HR for +1q patients vs. without (across both arms) showed worse OS and PFS for +1q. There is considerable heterogeneity in the reporting of +1q. All interventions that have shown to be successful in RCTs and have clearly reported on the +1q subgroup have shown concordant direction of results and benefit of the applied intervention. A more standardized approach to reporting this abnormality is needed.
1号染色体长臂2区1带额外拷贝（+1q：获得性增加=3个拷贝，扩增≥4个拷贝）与多发性骨髓瘤（MM）的不良预后相关。本系统性综述评估了当前随机对照试验（RCTs）中+1q的报告趋势、现有方案对+1q的疗效及其预后意义。检索了2012年1月至2022年12月期间的Pubmed、Embase和Cochrane RCT注册库，仅纳入MM相关RCT。共纳入124项RCT，其中29项（23%）研究报告了+1q。在这些研究中，10%明确定义了+1q的阈值，14%分别报告了获得性增加与扩增的生存数据，79%将+1q视为高危细胞遗传学异常。在达到主要终点（显示无进展生存期（PFS）改善）的RCT中，来那度胺维持治疗（Myeloma XI）、塞利尼索（BOSTON）以及伊沙妥昔单抗（IKEMA和ICARIA）被证实可改善存在+1q证据患者的PFS。另一些RCT如Myeloma XI+（卡非佐米）、ELOQUENT-3（埃罗妥珠单抗）和HOVON-65/GMMG-HD4（硼替佐米）同样达到改善PFS的终点，且在+1q亚组中也显示PFS改善，尽管其置信区间跨过1。所有六项报告+1q患者与非+1q患者（跨两组）风险比（HR）的研究均显示，+1q患者的总生存期（OS）和PFS更差。当前+1q的报告存在显著异质性。所有在RCT中显示成功且明确报告+1q亚组数据的干预措施，均呈现一致的结果方向和治疗获益。需要更标准化的异常报告方法。
Alterations in chromosome 1q in multiple myeloma randomized clinical trials: a systematic review
肿瘤(癌症)患者之家