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August 2, 2026Journal of Clinical Oncology

High-Risk Smoldering Multiple Myeloma: A Review of Controversies in Early Treatment Versus Observation

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Authors

MMMaría‐Victoria MateosUniversidad Complutense de MadridJGJoshua GustineGlobal Cancer InstituteBPBorja PuertasUniversidad de Salamanca

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Overview

Randomized trial evaluates early treatment versus observation in high-risk smoldering multiple myeloma, suggesting a shift in management strategies.

Key Points

  • This review aims to address the controversies surrounding early treatment versus observation in high-risk smoldering multiple myeloma.
  • Examined contemporary approaches to risk stratification including clinical variables, dynamic biomarkers, and genomic alterations.
  • Reviewed findings from randomized phase III trials, particularly the AQUILA trial involving daratumumab monotherapy.
  • Discussed patient-centered management considering individual risk levels and treatment responses.
  • Daratumumab demonstrated a significant progression-free survival benefit (HR, 0.49; 95% CI, 0.36 to 0.67; P < .001) versus observation.
  • Improved overall survival trend noted (HR, 0.52; 95% CI, 0.27 to 0.98) but remains inconclusive.
  • Emerging treatments like bispecific antibodies and CAR-T therapies show potential but require further investigation for long-term safety.

Cite This Study

Mateos et al. (2026) studied this question.

synapsesocial.com/papers/6a6eeb201b0468a7eeab3fd6https://doi.org/10.1200/jco-26-00236
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Daratumumab monotherapy versus active monitoring in patients with high-risk smoldering multiple myeloma: Aquila outcomes based on mayo 2018/IMWG 2020 risk stratification, IMWG 2020 plus cytogenetic criteria, and age2025 · 4 citations
  2. 2The evolving pattern of the monoclonal protein improves the IMWG 2/20/20 classification for patients with smoldering multiple myeloma2024 · 15 citations
  3. 3Evolution of multiple myeloma from a genomic perspective2025 · 7 citations
  4. 4Genomics Define Malignant Transformation in Myeloma Precursor Conditions2025 · 18 citations
  5. 5Prognostic Significance of Focal Lesions in Whole-Body Magnetic Resonance Imaging in Patients With Asymptomatic Multiple Myeloma2010 · 387 citations