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Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studies

Authors Zhao AL, Shen KN, Wang JN, Huo LQ, Li J, Cao XX

Received 16 February 2019

Accepted for publication 16 May 2019

Published 21 June 2019 Volume 2019:11 Pages 5599—5611

DOI https://doi.org/10.2147/CMAR.S205623

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 4

Editor who approved publication: Dr Ahmet Emre Eskazan


Ai-Lin Zhao,* Kai-Ni Shen,* Ji-Nuo Wang, Lan-Qing Huo, Jian Li, Xin-Xin Cao

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China

*These authors contributed equally to this work

Purpose: Smoldering multiple myeloma (SMM) is a rare asymptomatic plasma cell disorder. Even with emerging therapeutic approaches and risk stratification, the optimal time to treat SMM remains controversial. This meta-analysis aimed to compare early treatment with deferred treatment of SMM, especially high-risk SMM.
Methods: Early treatment was defined as treatment immediately after diagnosis. Deferred treatment was initiated after progression. The primary outcome was progression. Secondary outcomes were mortality, response, and safety. PubMed, EMBASE, Medline, Cochrane, and ClinicalTrials.gov databases were searched from January 1990 to March 2019. Randomized controlled trials (RCTs) comparing early treatment with deferred treatment in SMM patients were eligible. Risk ratios (RRs) with 95% confidence interval (CI) were pooled.
Results: Eight RCTs covering 885 SMM patients were included. Considering all the different treatment approaches, early treatment significantly decreased progression of SMM (RR=0.53, 95% CI 0.33–0.87, P=0.01). In subgroup analysis, melphalan plus prednisone (RR=0.22, 95% CI 0.08–0.64, P=0.005) and immuno-modulatory drugs (RR=0.43, 95% CI 0.31–0.59, P<0.00001) significantly reduced progression. However, neither mortality nor response rate was significantly affected by early treatment. In terms of high-risk SMM patients, early treatment significantly decreased both progression (RR=0.51, 95% CI 0.37–0.70, P=0.0001) and mortality (RR=0.53, 95% CI 0.29–0.96, P=0.04). Frequently seen adverse events were infection, constipation, asthenia, and second primary malignancy. A remarkably elevated risk of constipation was associated with early treatment using immuno-modulatory agents (RR=4.43, 95% CI 2.14–9.12, P<0.0001). Second primary malignancy was significantly increased with early treatment (RR=4.13, 95% CI 1.07–15.97, P=0.04). No significant difference was identified in infection or asthenia.
Conclusion: These findings suggest that early treatment could decrease progression and mortality of high-risk SMM patients with a tolerable safety profile.

Keywords: smoldering multiple myeloma, early treatment, lenalidomide, meta-analysis

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