Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis

Chi-Maw Lin; Lih-Chyun Chang; Wen-Yi Shau; Chi-Ling Chen; Chi-Yuan Yao; Feng-Ming Tien

doi:10.1186/s12885-023-10907-1

Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis

BMC Cancer. 2023 May 16;23(1):446. doi: 10.1186/s12885-023-10907-1.

Authors

Chi-Maw Lin^{1

2}, Lih-Chyun Chang^{1

3

4}, Wen-Yi Shau¹, Chi-Ling Chen¹, Chi-Yuan Yao^{1

5}, Feng-Ming Tien^{6

7}

Affiliations

¹ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Otolaryngology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan.
³ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City, 100225, Taiwan.
⁶ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. b92401007@gmail.com.
⁷ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City, 100225, Taiwan. b92401007@gmail.com.

Abstract

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.

Keywords: Autologous stem-cell transplantation; Meta-analysis; Multiple myeloma; Survival; Systematic review.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Disease-Free Survival
Hematopoietic Stem Cell Transplantation*
Humans
Male
Multiple Myeloma* / drug therapy
Multiple Myeloma* / therapy
Stem Cell Transplantation
Transplantation, Autologous