背景:阴燃多发性骨髓瘤(SMM),多发性骨髓瘤(MM)的无症状前兆,具有可变的进展至MM的风险。关于SMM的疗效或最佳治疗时机几乎没有共识。我们系统地回顾了SMM所有临床试验的情况。我们将SMM中研究的治疗方案的疗效与新诊断的多发性骨髓瘤(NDMM)中使用这些方案的结果进行了比较,以确定数据是否表明SMM与NDMM的反应更深。
方法:所有针对SMM的前瞻性介入临床试验,包括已发表的研究报告,会议摘要,并确定了截至2023年4月1日在ClinicalTrials.gov上列出的未发表的试验。捕获了与试验相关的变量,包括治疗策略和疗效结果。相关临床终点定义为总生存期(OS)和生活质量。
结果:在确定的45项SMM试验中,38(84.4%)评估了活性骨髓瘤药物,7(15.6%)仅研究了骨改性剂。在SMM的18项随机试验中,只有1个(5.6%)的主要终点为OS;最常见的主要终点为无进展生存期(n=7,38.9%).在32个有可用结果的SMM试验中,9人(28.1%)达到了预定的主要终点,其中5项为单臂研究。在SMM和NDMM中测试了6种治疗方案;与相应的NDMM试验相比,5种方案在SMM中产生了较低的非常好的部分缓解率或更好的(≥VGPR)(32%vs63%,43%vs53%,40%vs63%,86%vs89%,92%vs95%,94%和87%,分别)。
结论:在对SMM的所有前瞻性介入临床试验的系统综述中,我们在试验设计中发现了显著的可变性,包括随机化状态,主要终点,以及使用的干预类型。尽管有统计限制,治疗方案的比较没有令人信服的证据表明,与NDMM相比,在SMM早期引入治疗方案更有效.
BACKGROUND: Smoldering multiple
myeloma (SMM), an asymptomatic precursor of multiple
myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studied in SMM to results from these regimens when used in newly diagnosed multiple
myeloma (NDMM), to determine whether the data suggest deeper responses in SMM versus NDMM.
METHODS: All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified. Trial-related variables were captured, including treatment strategy and efficacy results. Relevant clinical endpoints were defined as overall survival (OS) and quality of life.
RESULTS: Among 45 SMM trials identified, 38 (84.4%) assessed active
myeloma drugs, while 7 (15.6%) studied bone-modifying agents alone. Of 18 randomized trials in SMM, only one (5.6%) had a primary endpoint of OS; the most common primary endpoint was progression-free survival (n = 7, 38.9%). Among 32 SMM trials with available results, 9 (28.1%) met their prespecified primary endpoint, of which 5 were single-arm studies. Six treatment regimens were tested in both SMM and NDMM; 5 regimens yielded a lower rate of very good partial response rate or better (≥VGPR) in SMM compared to the corresponding NDMM trial (32% vs 63%, 43% vs 53%, 40% vs 63%, 86% vs 89%, 92% vs 95%, and 94% vs 87%, respectively).
CONCLUSIONS: In this systematic review of all prospective interventional clinical trials in SMM, we found significant variability in trial design, including randomization status, primary endpoints, and types of intervention used. Despite the statistical limitations, comparison of treatment regimens revealed no compelling evidence that the treatment is more effective when introduced early in SMM compared to NDMM.