Abstract
OBJECTIVE: Smoldering multiple myeloma (SMM) is a slowly progressive, asymptomatic plasma cell disorder. This meta-analysis evaluated the efficacy and safety of novel agent-based therapies for SMM, particularly high-risk patients. METHODS: PubMed, Embase, Web of Science, Ovid MEDLINE, Scopus and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) and non-randomized studies from 2003 to 2024. RESULTS: Nineteen studies were included, comprising 5 RCTs and 14 non-randomized, single-arm trials. These studies involved a total of 1217 patients. Pooled analysis of intervention groups showed progression-free survival (PFS) and overall survival (OS) rate at 12 months of 94% (95% CI, 89%-98%) and 99% (95% CI, 97%-100%), respectively. The overall response rate (ORR) was 64% (95% CI, 50%-77%), and the complete response rate (CRR) was 12% (95% CI, 3%-25%). Minimal residual disease (MRD) negativity rate was 62% (95% CI, 42%-81%), and grade 3-4 adverse events (AEs) rate was 36% (95% CI, 30%-43%). As a comparison, we pooled data from the control groups of 5 RCTs, showing that PFS and OS rate-12m were 76% and 97%, respectively, with 0% CRR, 0% ORR and 25% grade 3-4 AEs. Subgroup analysis revealed high-risk SMM patients achieved higher PFS rate -12 m (97% vs. 91%), ORR (77% vs. 53%) and CRR (24% vs. 5%) compared to all SMM patients, with similar OS rate-12m (99% vs. 99%) and AEs rates (38% vs. 34%). CONCLUSION: Early intervention may delay progression and improve clinical responses, especially in high-risk SMM. However, adverse events (AEs) warrant caution. More well-designed RCTs are needed to confirm our findings.