Kakkilaya Apoorva, Trando Aaron, Cliff Edward R Scheffer, Mian Hira, Al Hadidi Samer, Aziz Muhammad, Goodman Aaron M, Jeong Ah-Reum, Smith Wade L, Kelkar Amar H, Russler-Germain David A, Mehra Nikita, Chakraborty Rajshekhar, Gertz Morie A, Mohyuddin Ghulam Rehman
John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, United States.
School of Medicine, University of California San Diego, La Jolla, CA, United States.
Oncologist. 2025 Feb 6;30(2). doi: 10.1093/oncolo/oyae219.
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.
All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified.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.
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).
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.
冒烟型多发性骨髓瘤（SMM）是多发性骨髓瘤（MM）的无症状前驱疾病，进展为MM的风险各异。关于SMM治疗的疗效或最佳时机，目前几乎没有共识。我们系统回顾了SMM的所有临床试验情况。我们将SMM中研究的治疗方案的疗效与这些方案用于新诊断的多发性骨髓瘤（NDMM）时的结果进行比较，以确定数据是否表明SMM与NDMM相比有更深的缓解。
确定了所有针对SMM的前瞻性干预性临床试验，包括已发表的研究、会议摘要以及截至2023年4月1日在ClinicalTrials.gov上列出的未发表试验。记录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。
在所确定的45项SMM试验中，38项（84.4%）评估了活性骨髓瘤药物，而7项（15.6%）仅研究了骨改良剂。在SMM的18项随机试验中，只有1项（5.6%）的主要终点是OS；最常见的主要终点是无进展生存期（n = 7，38.9%）。在32项有可用结果的SMM试验中，9项（28.1%）达到了预先设定的主要终点，其中5项是单臂研究。在SMM和NDMM中都测试了六种治疗方案；与相应的NDMM试验相比，5种方案在SMM中产生的非常好的部分缓解率或更好缓解率（≥VGPR）较低（分别为32%对63%、43%对53%、40%对63%、86%对89%、92%对95%以及94%对87%）。
在对SMM所有前瞻性干预性临床试验的这项系统回顾中，我们发现试验设计存在显著差异，包括随机化状态、主要终点和所使用的干预类型。尽管存在统计局限性，但治疗方案的比较没有显示出令人信服的证据表明与NDMM相比，在SMM早期引入治疗更有效。
