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Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis
BACKGROUND: Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10190007/ https://www.ncbi.nlm.nih.gov/pubmed/37193978 http://dx.doi.org/10.1186/s12885-023-10907-1 |
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author | Lin, Chi-Maw Chang, Lih-Chyun Shau, Wen-Yi Chen, Chi-Ling Yao, Chi-Yuan Tien, Feng-Ming |
author_facet | Lin, Chi-Maw Chang, Lih-Chyun Shau, Wen-Yi Chen, Chi-Ling Yao, Chi-Yuan Tien, Feng-Ming |
author_sort | Lin, Chi-Maw |
collection | PubMed |
description | BACKGROUND: Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT. METHODS: We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023. Further sensitivity analysis and meta-regression were also performed. RESULTS: Among the 22 enrolled studies, 7 RCTs and 9 observational studies had a low or moderate risk of bias, while the remaining 6 observational studies had a serious risk of bias. HDT/ASCT revealed advantages in complete response (CR) with an odds ratio (OR) of 1.24 and 95% confidence interval (CI) 1.02 ~ 1.51, PFS with a hazard ratio (HR) of 0.53 (95% CI 0.46 ~ 0.62), and OS with an HR of 0.58 (95% CI 0.50 ~ 0.69). Sensitivity analysis excluding the studies with serious risk of bias and trim-and-fill imputation fundamentally confirmed these findings. Older age, increased percentage of patients with International Staging System (ISS) stage III or high-risk genetic features, decreased proteasome inhibitor (PI) or combined PI/ immunomodulatory drugs (IMiD) utilization, and decreased follow-up duration or percentage of males were significantly related to a greater survival advantage with HDT/ASCT. CONCLUSIONS: Upfront ASCT remains a beneficial treatment for newly diagnosed MM patients in the period of novel agents. Its advantage is especially acute in high-risk MM populations, such as elderly individuals, males, those with ISS stage III or high-risk genetic features, but is attenuated with PI or combined PI/IMiD utilization, contributing to divergent survival outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10907-1. |
format | Online Article Text |
id | pubmed-10190007 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101900072023-05-18 Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis Lin, Chi-Maw Chang, Lih-Chyun Shau, Wen-Yi Chen, Chi-Ling Yao, Chi-Yuan Tien, Feng-Ming BMC Cancer Research BACKGROUND: Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT. METHODS: We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023. Further sensitivity analysis and meta-regression were also performed. RESULTS: Among the 22 enrolled studies, 7 RCTs and 9 observational studies had a low or moderate risk of bias, while the remaining 6 observational studies had a serious risk of bias. HDT/ASCT revealed advantages in complete response (CR) with an odds ratio (OR) of 1.24 and 95% confidence interval (CI) 1.02 ~ 1.51, PFS with a hazard ratio (HR) of 0.53 (95% CI 0.46 ~ 0.62), and OS with an HR of 0.58 (95% CI 0.50 ~ 0.69). Sensitivity analysis excluding the studies with serious risk of bias and trim-and-fill imputation fundamentally confirmed these findings. Older age, increased percentage of patients with International Staging System (ISS) stage III or high-risk genetic features, decreased proteasome inhibitor (PI) or combined PI/ immunomodulatory drugs (IMiD) utilization, and decreased follow-up duration or percentage of males were significantly related to a greater survival advantage with HDT/ASCT. CONCLUSIONS: Upfront ASCT remains a beneficial treatment for newly diagnosed MM patients in the period of novel agents. Its advantage is especially acute in high-risk MM populations, such as elderly individuals, males, those with ISS stage III or high-risk genetic features, but is attenuated with PI or combined PI/IMiD utilization, contributing to divergent survival outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10907-1. BioMed Central 2023-05-16 /pmc/articles/PMC10190007/ /pubmed/37193978 http://dx.doi.org/10.1186/s12885-023-10907-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Lin, Chi-Maw Chang, Lih-Chyun Shau, Wen-Yi Chen, Chi-Ling Yao, Chi-Yuan Tien, Feng-Ming Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis |
title | Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis |
title_full | Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis |
title_fullStr | Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis |
title_full_unstemmed | Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis |
title_short | Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis |
title_sort | treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10190007/ https://www.ncbi.nlm.nih.gov/pubmed/37193978 http://dx.doi.org/10.1186/s12885-023-10907-1 |
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