Mohyuddin Ghulam Rehman, Almasri Jehad, Goodman Aaron, Haslam Alyson, Prasad Vinay
Division of Hematology, Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT 84112, United States.
Division of Hematology, University of Cincinnati, Cincinnati, OH 45221, United States.
Oncologist. 2025 Jul 4;30(7). doi: 10.1093/oncolo/oyae332.
Prior studies have evaluated the level of evidence behind treatment options listed in the National Comprehensive Cancer Network (NCCN) guidelines, but no study has categorized the life cycle of regimens listed in the NCCN guidelines. We longitudinally assessed the life cycle for each regimen for newly diagnosed multiple myeloma. We track the date of first clinical data, the date of regimen addition to NCCN guidelines, the date phase 3 data (if performed) were reported, and the results of phase 3 trials.
We systematically examined NCCN guidelines from January 2000 to April 2021. The primary objective of our study was to assess the life cycle of each drug/regimen listed on the NCCN guidelines. We systematically examined the following aspects for each regimen: (1) the inception of prospective clinical data, (2) its inclusion in the NCCN guidelines, (3) the completion of a randomized trial (if done), (4) the presence of an overall survival benefit in such trials, and (5) the removal of a regimen from NCCN guidelines (if done) and its corresponding timeline.
Twenty-one regimens were added across 50 NCCN guideline document iterations during a 22-year period. The median time from when clinical data were first presented to when a regimen was first listed in the guidelines was 15 months. Phase 3 studies were conducted for 17 regimens (80%), with a surrogate endpoint (response rate or progression-free survival) as endpoint for all trials, other than one. The median time from a regimen being included in the NCCN guideline to its phase 3 data publication was 43 months. The primary endpoint was met for 13 trials (81%). No regimen was removed for a phase 3 endpoint not being met. Six regimens (38%) showed overall survival benefit. Five (23%) regimens were removed from NCCN guidelines, with none being due to failure in phase 3 testing.
Myeloma NCCN guidelines remain relevant and current, adding new regimens with promising early-phase data, and removing regimens that become obsolete over time. However, this process is inconsistent and may benefit from standardization.
先前的研究评估了美国国立综合癌症网络（NCCN）指南中列出的治疗方案背后的证据水平，但尚无研究对NCCN指南中列出的治疗方案的生命周期进行分类。我们纵向评估了新诊断多发性骨髓瘤每种治疗方案的生命周期。我们追踪首次临床数据的日期、该方案被纳入NCCN指南的日期、3期数据（如果进行了）报告的日期以及3期试验的结果。
我们系统地审查了2000年1月至2021年4月的NCCN指南。我们研究的主要目的是评估NCCN指南中列出的每种药物/治疗方案的生命周期。我们系统地审查了每种治疗方案的以下方面：（1）前瞻性临床数据的起始，（2）其被纳入NCCN指南，（3）随机试验的完成（如果进行了），（4）此类试验中总体生存获益的存在，以及（5）从NCCN指南中删除一种治疗方案（如果进行了）及其相应的时间线。
在22年期间的50次NCCN指南文件迭代中增加了21种治疗方案。从首次公布临床数据到该方案首次在指南中列出的中位时间为15个月。对17种治疗方案（80%）进行了3期研究，除一项试验外，所有试验均以替代终点（缓解率或无进展生存期）作为终点。从一种治疗方案被纳入NCCN指南到其3期数据发表的中位时间为43个月。13项试验（81%）达到了主要终点。没有因为未达到3期终点而删除任何治疗方案。六种治疗方案（38%）显示出总体生存获益。五种（23%）治疗方案从NCCN指南中删除，没有一种是因为3期试验失败。
骨髓瘤NCCN指南仍然相关且与时俱进，增加了具有前景的早期数据的新治疗方案，并删除了随着时间推移而过时的治疗方案。然而，这个过程并不一致，可能受益于标准化。
