Supplementary Material for: Effectiveness of Long-Term Treatment of Multiple Myeloma in Regular Care: Comparison of a Longitudinal and a Cross-Sectional Analysis Approach

<b><i>Introduction:</i></b> New drugs for multiple myeloma have considerably increased the options for consecutive treatment lines in regular care. Official treatment guidelines still discuss several regimens per line, and therefore, current practice is of topical interest. Large cross-sectional studies revealed a greater than linear loss of patients reaching consecutive treatment lines of ever decreasing effectiveness. <b><i>Methods:</i></b> In a longitudinal approach, we analyzed data of all 145 multiple myeloma patients treated in our outpatient clinic in Germany between January 1, 2012, and December 31, 2019, using a time-to-event analysis with death as competitive risk. <b><i>Results:</i></b> The estimated incidences of reaching the 2nd, 3rd, 4th, and 5th lines of therapy were 88, 66, 44, and 30%, respectively. Median times to subsequent treatment lines were 34, 18, 14, 13, and 15 months, respectively. <b><i>Discussion:</i></b> Percentages of patients reaching later therapy lines were considerably greater than predicted by cross-sectional studies and median times after the 1st line did not suggest a further decrease in effectiveness, while use of new drug regimens was similar to that reported in cross-sectional studies. <b><i>Conclusion:</i></b> Effectiveness of later therapy lines appears to be underestimated by cross-sectional analyses, and the conveyed focus on 1st-line treatment for multiple myeloma needs to be scrutinized.

<b><i>引言：</i></b> 多发性骨髓瘤（multiple myeloma）的新型药物极大拓展了常规临床诊疗中连续治疗线的选择空间。目前官方治疗指南仍针对每一治疗线推荐多种方案，因此当前的临床实践是学界关注的热点。既往大型横断面研究（cross-sectional studies）显示，能够接受后续治疗线且疗效持续递减的患者比例呈超线性下降。<b><i>方法：</i></b> 本研究采用纵向研究方法，分析了2012年1月1日至2019年12月31日期间于德国我院门诊就诊的全部145例多发性骨髓瘤患者的临床数据，以死亡作为竞争风险（competitive risk）开展时间-事件分析（time-to-event analysis）。<b><i>结果：</i></b> 本研究估计，患者接受第2、3、4、5线治疗的发生率分别为88%、66%、44%和30%；各后续治疗线的中位时间依次为34、18、14、13和15个月。<b><i>讨论：</i></b> 本研究中，能够接受后续治疗线的患者比例显著高于横断面研究的预测结果；一线治疗后的中位间隔时间并未显示出疗效进一步下降的趋势，而新型药物治疗方案的使用情况与横断面研究的报道基本一致。<b><i>结论：</i></b> 横断面分析似乎低估了后线治疗的疗效，当前针对多发性骨髓瘤一线治疗的研究焦点亟需重新审视。