How Could Early Treatment Benefit Patients With Smoldering Multiple Myeloma?

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Early treatment, in comparison to deferred treatment, of patients with smoldering multiple myeloma could reduce progression and mortality.

Early treatment of high-risk patients with smoldering multiple myeloma (SMM) with tolerable safety profiles could reduce progression to MM and mortality, according to a review article in Dovepress. Low- and intermediate-risk SMM patients may only experience decreased progression with early treatment.

“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,” researchers said.

In the study, early treatment was defined as treatment initiated immediately after diagnosis while deferred treatment began after progression to MM. Researchers examined differences in progression, mortality, response rates, and safety between early and deferred treatment in patients with SMM. They also performed subgroup analysis on high-risk patients and on different types of treatment to assess the benefits and risks for patients in order to identify the most suitable therapy.

The study’s primary outcome was disease progression. Secondary outcomes included mortality, response, and safety. A literature search of PubMed, EMBASE, Medline, Cochrane, and databases was performed by 2 investigators from January 1990 to March 2019 using synonyms of the keywords smoldering multiple myeloma, asymptomatic multiple myeloma, early stage multiple myeloma, progression, death, survival, response, and safety. Only studies written in English were included.


Randomized controlled trials (RCTs) that compared early treatment with deferred treatment of patients with SMM were eligible for inclusion. The titles and abstracts for potential studies were independently screened by 2 investigators. The database search yielded 258 studies. A total of 8 RCTs that covered 885 patients with SMM were included in the meta-analysis.

SMM patients were included altogether with or without risk stratifications and weren’t previously treated. Mortality was examined from randomization until all-cause death. Response was assessed by objective response rate. Studies were excluded if they only compared 2 different dosages of the same early treatment instead of comparing early treatment with deferred treatment. Cohort studies, case reports, case series, cross-sectional studies, letters, reviews, short surveys, editorials, and studies written in a language other than English were also excluded.

Researchers used Review Manager 5.3 from the Cochrane Collaboration to conduct the meta-analysis. Risk ratios (RRs) were pooled with 95% confidence interval. The Mantel-Haenszel method was used to calculate the pooled RRs. Heterogeneity was assessed using the I2 statistic. When significant heterogeneity was found, in studies with I2 greater than 50%, researchers used random effects models and carried out subgroup and sensitivity analyses. In the absence of significant heterogeneity, fixed-effects models were used. Effects were considered significant when P was less than 0.05.

After considering all treatment approaches, researchers found that early treatment significantly decreased progression of SMM. In subgroup analysis, melphalan plus prednisone and immunomodulatory drugs were found to significantly reduce progression. Mortality and response rate were found to not be significantly affected by early treatment. For high-risk SMM patients, early treatment significantly decreased both progression and mortality.

“In conclusion, our study reveals that high-risk SMM patients could benefit from early treatment in reducing progression and mortality,” researchers said. “In terms of low-risk and intermediate-risk SMM patients, progression could be reduced by early treatment, but there is inadequate evidence that mortality could be reduced. The number of included RCTs is limited, and future studies which unify risk models with larger sample size are needed to confirm the conclusion.”

Researchers suggested future studies that explore different interventions for high-risk SMM patients are needed. They also stressed the necessity to unify risk models to better manage SMM patients.


Zhao AL, Shen KN, Wang JN, Huo LQ, Li, J, Cao XX. Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studies. Dove Press. 2019;11:5599-5611. doi: 10.2147/CMAR.S205623.