Department of Hematology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Blood Cancer J. 2021 Mar 1;11(3):44. doi: 10.1038/s41408-021-00441-3.
Great progress in the treatment of patients with multiple myeloma (MM) has been made due to the development of novel drugs. Patients with relapsed/refractory MM (RRMM) can be enrolled in early-phase clinical trials, but their performance across the last decade is unknown. We conducted a meta-analysis on the overall response rate (ORR) and toxicity. PubMed, Embase, and Cochrane Library were systematically searched for phase I and phase II trials investigating an experimental compound as a single agent or in combination with dexamethasone, published from January 1, 2010 to July 1, 2020. Eighty-eight articles were included, describing 61 phase I trials involving 1835 patients and 37 phase II trials involving 2644 patients. There was a high degree of heterogeneity. Using a random-effects model, the 95% CIs of the estimated ORR were 8-17% for phase I trials and 18-28% for phase II trials. There were significant subgroup differences in ORR between the years of publication in phase I trials and between drug classes in both phase I and phase II trials. The ORR in early-phase clinical trials in RRMM is substantial, especially in phase II trials, but due to high heterogeneity a general assessment of clinical benefit before participation is difficult to offer to patients.
由于新型药物的发展，多发性骨髓瘤（MM）患者的治疗取得了重大进展。复发/难治性 MM（RRMM）患者可以入组早期临床试验，但过去十年的表现尚不清楚。我们对总缓解率（ORR）和毒性进行了荟萃分析。系统地检索了 PubMed、Embase 和 Cochrane Library 中 2010 年 1 月 1 日至 2020 年 7 月 1 日期间发表的关于作为单一药物或与地塞米松联合使用的实验化合物的 I 期和 II 期临床试验，研究对象为 RRMM 患者。共纳入 88 篇文章，描述了 61 项 I 期试验，涉及 1835 例患者和 37 项 II 期试验，涉及 2644 例患者。存在高度异质性。使用随机效应模型，I 期试验中估计的 ORR 的 95%CI 为 8-17%，II 期试验中为 18-28%。I 期试验中发表年份和 I 期和 II 期试验中药物类别之间的 ORR 存在显著亚组差异。RRMM 早期临床试验中的 ORR 相当高，尤其是 II 期试验，但由于高度异质性，很难在患者参与之前对其临床获益进行总体评估。
