REVIEW article
Front. Hematol.
Sec. Blood Cancer
This article is part of the Research TopicAdvances and New Horizons in Cellular Therapies for Leukemia and MyelomaView all 4 articles
To Treat or Not to Treat: A State-of-the-Art Overview of Smoldering Multiple Myeloma
Provisionally accepted
- 1Wayne State University School of Medicine, Detroit, United States
- 2The Ohio State University, Columbus, United States
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Smoldering multiple myeloma (SMM) is a plasma cell disorder characterized by an elevated monoclonal protein and increased bone marrow plasma cells (BMPC) without end-organ damage. It is an intermediate stage on the spectrum of plasma cell disorders, between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic (active) multiple myeloma (MM). While most patients remain asymptomatic for years, a high-risk subset progresses rapidly. Traditional “watch-and-wait” strategy while avoiding toxicities associated with unnecessary therapy, can potentially delay treatment in those at increased risk for progression to MM associated with painful bone lesions, anemia, kidney failure and hypercalcemia. Hence, selection of the appropriate patient for treatment by accurate determination of individual risk of progression is vital in improving outcomes while avoiding toxicity. This review discusses the risk-stratification methods and evaluate various clinical therapeutic interventions for high-risk SMM, including immunomodulatory drugs, monoclonal antibodies, bispecific antibodies, and Chimeric Antigen Receptor- T cell (CAR-T) therapies along with their outcomes, safety profiles and limitations. We also discuss the importance of shared decision-making between clinicians and patients, tailoring monitoring and treatment to individual preferences to ensure that each patient receives maximum benefit and minimum harm.
Keywords: Cytogenetics, High-risk smoldering myeloma, Immunomodulatory drugs, Plasma Cells, smoldering multiple myeloma
Received: 15 Sep 2025; Accepted: 11 Dec 2025.
Copyright: © 2025 Garg and Devarakonda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ayushi Garg
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