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. 2019 Jun 21:11:5599-5611.
doi: 10.2147/CMAR.S205623. eCollection 2019.

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

Ai-Lin Zhao #  1 , Kai-Ni Shen #  1 , Ji-Nuo Wang  1 , Lan-Qing Huo  1 , Jian Li  1 , Xin-Xin Cao  1
Affiliations

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

Ai-Lin Zhao et al. Cancer Manag Res. .

Abstract

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: early treatment; lenalidomide; meta-analysis; smoldering multiple myeloma.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study flow diagram. Abbreviation: RCT, randomized controlled trial.
Figure S1
Figure S1
Risk of bias summary.
Figure 2
Figure 2
Progression in overall SMM patients. Abbreviations: MP, melphalan-prednisone; IMiD, immunomodulatory drug; SMM, smoldering multiple myeloma.
Figure S2
Figure S2
Skeletal-related events of overall SMM patients at progression. Abbreviation: SMM, smoldering multiple myeloma.
Figure 3
Figure 3
Mortality in overall SMM patients. Abbreviations: MP, melphalan-prednisone; IMiD, immunomodulatory drug; SMM, smoldering multiple myeloma.
Figure 4
Figure 4
Therapeutic response in overall SMM patients. Abbreviation: SMM, smoldering multiple myeloma.
Figure 5
Figure 5
(A) Progression and (B) mortality in high-risk SMM patients. Abbreviation: SMM, smoldering multiple myeloma.
Figure S3
Figure S3
(A) Infection, (B) asthenia, (C) constipation, and (D) second primary malignancy in overall SMM patients. Abbreviation: SMM, smoldering multiple myeloma.
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