Journal Article Epublish
PubMed: 41567715 DOI: 10.1016/j.eclinm.2025.103750
Temporal trends in progression risk in smoldering myeloma: a systematic review.
EClinicalMedicine 91:103750
Authors: Heinz Ludwig, Efstathios Kastritis, Sarah Bernhard, Niels W C J van de Donk, Mario Boccadoro, Evangelos Terpos, Pellegrino Musto, Pieter Sonneveld, Ghulam Rehman Mohyuddin
Affiliations
- Wilhelminen Cancer Research Institute, First Department of Medicine, Center for Oncology, Hematology, and Palliative Care, Clinic Ottakring, Montlearstraße 37, 1160, Vienna, Austria.
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 80 Vas. Sofias & Lourou St. 11528, Athens, Greece.
- Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
- Department of Molecular Biotechnology and Health Science, European Myeloma Network (EMN), University of Torino, Via Nizza, 52, 10126, Turin, Italy.
- Department of Precision and Regenerative Medicine and Ionian Area, "Aldo Moro" University School of Medicine, Piazza Giulio Cesare, 11, 70124, Bari, Italy.
- Unit of Hematology and Stem Cell Transplantation, AOU Consorziale Policlinico, Piazza Giulio Cesare, 11, 70124, Bari, Italy.
- Department of Hematology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
- Division of Hematology, Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Dr. Salt Lake City, UT, 84112, USA.
Abstract
BACKGROUND
Diagnostic advancements and classification updates appear to have reshaped the natural history of smoldering multiple myeloma (SMM), though this evolution has not been empirically quantified. We conducted a systematic review to evaluate temporal changes in SMM prognosis.
METHODS
PubMed, EMBASE and the Cochrane library databases were searched from January 1990 to November 2025, yielding 1415 reports, of which 14 studies met inclusion criteria. To reconstruct individual-level data, published time to progression (TTP) curves were digitized using a Shiny web application. Kaplan-Meier (KM) survival curves and meta-analyses were generated in RStudio. PROSPERO ID 1068697.
FINDINGS
Progression risk at two and ten years for all-risk patients was 22.8% and 60.1%, respectively; these increased to 44.7% and 85.6% in high-risk patients. Landmark analysis from year five revealed attenuated progression rates: 14.2% and 30.8% for all-risk, and 22.5% and 50.6% for high-risk patients at two and five years post-landmark, respectively. Studies enrolling most patients before 2014 showed higher progression rates than in more recent cohorts (Spearman's rho = 0.645, p = 0.034), but this trend did not reach statistical significance in high-risk groups (rho = 0.360, p = 0.272). Meta-analytic data further supported elevated progression in older cohorts.
INTERPRETATION
SMM appears to follow a more indolent trajectory in recent years, likely due to improved diagnostic precision and exclusion of biomarker-defined or subclinical MM. Enhanced predictive models may better guide therapeutic decision-making, targeting treatment to those most likely to benefit and avoiding the burden of unnecessary intervention in low-risk individuals.
FUNDING
Supported by the Austrian Forum Against Cancer.
MeSH
Therapeutics, Smoldering Multiple Myeloma