Genomically Smoldering Multiple Myeloma Is Not a Distinct Entity But a Collection of Monoclonal Gammopathy of Undetermined Significance or Multiple Myeloma

作者：Anıl Aktaş Samur, Jill Corre, Srikanth Talluri, Parth S Shah, Antoine Graffeuil, Joshua Rivera, Yiyang Fan, Bahar Dakiki, Raphael E. Szalat, Mariateresa Fulciniti, Kenneth Carl Anderson, Adam Samuel Sperling, Giovanni Parmigiani, Hervé Avet‐Loiseau, Nikhil C. Munshi, Mehmet Samur · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-00289 · 被引用次数：10 · 研究领域：Multiple Myeloma Research and Treatments、Acute Myeloid Leukemia Research、Myeloproliferative Neoplasms: Diagnosis and Treatment

PURPOSE: The diagnosis of smoldering multiple myeloma (SMM) primarily relies on clinical features such as plasma cell involvement, immunoglobulin protein levels, and end-organ damage. However, as early intervention becomes a priority, the role of genomic features in differentiating risk is gaining attention. METHODS: This study analyzed next-generation sequencing data from 224 precursor condition samples with 51 patients having paired SMM and multiple myeloma (MM) and 1,779 samples from newly diagnosed MM to identify genomic features linked to progression in SMM and those with a low-risk nonprogressor precursor condition. RESULTS: Our findings from paired samples revealed no significant differences in somatic alterations and clonal structures between SMM and MM samples from the same patient. This indicates that plasma cells in progressor SMM are genomically pre-equipped with changes that define myeloma. Over 80% of driver mutations were present at both time points, and more than 66% of progressor samples showed only minor clonal changes. We further compared genomic changes between nonprogressor and progressor SMM. Nonprogressor plasma cells showed significantly lower mutational load and the absence of copy number alterations on chromosome 8. They reduced focal genomic loss compared with progressor plasma cells. A scoring system using genomic features predictively identified patients with low-risk SMM unlikely to progress, validated on 101 additional independent samples, and a...