Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studies
Ai-Lin Zhao,* Kai-Ni Shen,* Ji-Nuo Wang, Lan-Qing Huo, Jian Li, Xin-Xin CaoDepartment 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 wo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-06-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/early-or-deferred-treatment-of-smoldering-multiple-myeloma-a-meta-anal-peer-reviewed-article-CMAR |
| _version_ | 1811270305604173824 |
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| author | Zhao AL Shen KN Wang JN Huo LQ Li J Cao XX |
| author_facet | Zhao AL Shen KN Wang JN Huo LQ Li J Cao XX |
| author_sort | Zhao AL |
| collection | DOAJ |
| description | Ai-Lin Zhao,* Kai-Ni Shen,* Ji-Nuo Wang, Lan-Qing Huo, Jian Li, Xin-Xin CaoDepartment 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 |
| first_indexed | 2024-04-12T21:58:30Z |
| format | Article |
| id | doaj.art-80fb0cfd4e4a4b169e45326997b013a4 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-04-12T21:58:30Z |
| publishDate | 2019-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-80fb0cfd4e4a4b169e45326997b013a42022-12-22T03:15:12ZengDove Medical PressCancer Management and Research1179-13222019-06-01Volume 115599561146565Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studiesZhao ALShen KNWang JNHuo LQLi JCao XXAi-Lin Zhao,* Kai-Ni Shen,* Ji-Nuo Wang, Lan-Qing Huo, Jian Li, Xin-Xin CaoDepartment 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-analysishttps://www.dovepress.com/early-or-deferred-treatment-of-smoldering-multiple-myeloma-a-meta-anal-peer-reviewed-article-CMARSmoldering multiple myelomaEarly treatmentLenalidomideMeta-analysis |
| spellingShingle | 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 Cancer Management and Research Smoldering multiple myeloma Early treatment Lenalidomide Meta-analysis |
| title | Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studies |
| title_full | Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studies |
| title_fullStr | Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studies |
| title_full_unstemmed | Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studies |
| title_short | Early or deferred treatment of smoldering multiple myeloma: a meta-analysis on randomized controlled studies |
| title_sort | early or deferred treatment of smoldering multiple myeloma a meta analysis on randomized controlled studies |
| topic | Smoldering multiple myeloma Early treatment Lenalidomide Meta-analysis |
| url | https://www.dovepress.com/early-or-deferred-treatment-of-smoldering-multiple-myeloma-a-meta-anal-peer-reviewed-article-CMAR |
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