PDF(Pubmed)
Abstract：
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.
摘要：
染色体1q21的额外拷贝(+1q:gain=3个拷贝,amp>=4个拷贝）与多发性骨髓瘤（MM）的不良预后相关。本系统综述评估了+1季度的当前报告趋势，现有方案在+1q上的疗效，及其在MM随机对照试验(RCTs)中的预后意义。Pubmed,从2012年1月至2022年12月检索Embase和CochraneRCT注册。仅包括MM随机对照试验。总共包括124项RCT，其中29项（23%）研究报告为+1q。其中,+1q的10%定义阈值，14%分别报告了增益和放大器的生存数据，79％的人认为+1q是高风险的细胞遗传学异常。在达到主要终点的RCT中，无进展生存期（PFS）有所改善，来那度胺维持（XI骨髓瘤），selinexor（波士顿），和伊沙妥昔单抗(IKEMA和ICARIA)被证明可以改善有+1q证据的患者的PFS。一些额外的RCT，如骨髓瘤XI+(卡非佐米)，ELOQUENT-3（elotuzumab），和HOVON-65/GMMG-HD4（硼替佐米）达到其终点，显示PFS改善，并且在+1q队列中也显示PFS改善，虽然置信区间交叉1。所有六项研究报告了+1q患者的HR与没有(在两个臂上)的+1q显示更差的OS和PFS。+1q的报告存在相当大的异质性。所有在随机对照试验中显示成功并在+1q亚组明确报道的干预措施都显示出一致的结果方向和应用干预措施的益处。需要一种更标准化的方法来报告这种异常。
