Introduction Although myeloma represents a key success story in oncology, some drugs have failed to meet primary endpoints in randomized controlled trials (RCTs), despite promising early-phase activity. This analysis aimed to understand factors that increase the likelihood of meeting primary endpoints in myeloma RCTs. Methods Myeloma RCTs published through October 2023 were identified using MEDLINE, PubMed, Embase, and the Cochrane Registry. Studies were classified as head-to-head (substituting one regimen for another) or add-on (adding one drug to existing regimen). Trials were considered successful if they achieved statistical significance for primary outcomes. Logistic regression identified predictors of meeting trial endpoints. Results A total of 145 comparisons from 123 RCTs were included. Only two factors were independently associated with meeting primary endpoints in multivariate analysis. Higher median participant age was associated with lower odds of meeting the primary endpoint (OR per one-year increase, 0.90, 95% CI: 0.83–0.98). Overall survival (OS) was the primary endpoint in 20/145 comparisons, of which 3/20 met their endpoint. Selecting OS as primary endpoint was associated with reduced likelihood of success compared with progression-free survival by 94% (OR: 0.06, 95% CI: 0.01–0.23). Head-to-head design was not associated with lower success rates than add-on design (OR: 0.59; 95% CI: 0.22-1.62). Conclusion Two key factors predicted higher likelihood of meeting endpoints: younger patient age and primary endpoints other than overall survival. Although head-to-head design is considered riskier, it was not associated with decreased success. This analysis aims to better inform clinicians, industry, and regulators in myeloma drug development.

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优化肿瘤药物开发：22年骨髓瘤随机对照试验的系统评价

引言 尽管骨髓瘤代表了肿瘤学的一个关键成功案例，但尽管早期活性良好，但一些药物未能达到随机对照试验 （randomized controlled trials， RCT） 的主要终点。该分析旨在了解增加骨髓瘤随机对照试验中达到主要终点可能性的因素。方法 使用 MEDLINE、PubMed、Embase 和 Cochrane Registry 确定截至 2023 年 10 月发表的骨髓瘤随机对照试验。研究被分为头对头（用一种方案代替另一种方案）或附加疗法（在现有方案中添加一种药物）。如果试验对主要结局具有统计学意义，则认为试验是成功的。逻辑回归确定了达到试验终点的预测因素。结果 共纳入 123 项 RCT 的 145 篇比较。在多变量分析中，只有两个因素与达到主要终点独立相关。受试者年龄中位数越高，达到主要终点的几率越低（OR/1 年增加，0.90,95%CI：0.83-0.98）。总生存期 （OS） 是 20/145 比较的主要终点，其中 3/20 达到终点。与无进展生存期相比，选择 OS 作为主要终点与成功的可能性降低 94%相关（OR：0.06,95%CI：0.01–0.23）。头对头设计与附加设计的成功率无关（OR：0.59;95% CI：0.22-1.62）。结论 预测达到终点的可能性较高的两个关键因素：患者年龄较小和总生存期以外的主要终点。尽管头对头设计被认为风险较大，但它与成功率下降无关。该分析旨在更好地为临床医生、行业和监管机构提供骨髓瘤药物开发的信息。