Mapping the Landscape of Quality of Life in Smoldering Multiple Myeloma Clinical Trials: A Systematic Review.

The therapeutic approach to smoldering multiple myeloma (SMM) is shifting from observation to early treatment, particularly in patients at high-risk of progression. Patients with SMM may experience factors that can negatively affect health-related quality of life (HRQoL). In addition, early therapeutic interventions may themselves impact HRQoL. Given these considerations, we aim to evaluate the assessment of HRQoL in clinical trials involving patients with SMM receiving treatment. We searched MEDLINE, Scopus, Web of Science, EMBASE, PubMED, and Cochrane Central Register of Controlled Trials for clinical trials assessing pharmacological interventions in patients with SMM from inception to July 2025. Study eligibility, data extraction and risk of bias assessment were conducted independently and in duplicate. The quality of evidence was assessed with the ROB-2 (risk of bias) assessment for randomized clinical trials. This study is registered on PROSPERO (CRD420251112091). The lack of consistent HRQoL assessment across trials stands out as a critical finding. Four randomised clinical trials evaluated HRQoL, although only 2 provided enough detail. Both the AQUILA and ECOG-ACRIN trials reported improvements in HRQoL; however, these benefits appeared to be treatment specific. However, despite these findings, most studies did not include HRQoL outcomes, highlighting a significant gap. This omission represents not only a methodological limitation but also as an ethical issue, given the importance of understanding treatment impact on patients' lives'. As therapeutic strategies continue to expand, the systematic incorporation of HRQoL outcomes is essential to support balanced and patient-centered decision-making.