Impact of Autologous Transplantation on Survival in Patients with Newly Diagnosed Multiple Myeloma Who Have High-risk Cytogenetics: A Meta-analysis of Randomized Controlled Trials

Background: Despite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high-dose therapy (HDT) consolidation on overall survival (OS) or progression-free survival (PFS) in patients who have high-risk cytogenetics. The authors performed a meta-analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk.

Methods: All RCTs in patients who had newly diagnosed myeloma from 2000 to 2021 that compared upfront HDT versus standard-dose therapy (SDT) consolidation were included. The primary objective was to assess the difference in HDT efficacy between standard-risk and high-risk cytogenetics in terms of the OS or PFS log(hazard ratio) (HR). The pooled OS and PFS HR was calculated according to cytogenetic-risk subgroup using a random-effects model, and heterogeneity (I ) (the percentage of total observed variability explained by between-study differences) was assessed using an interaction test.

Results: After screening 3307 citations, 6 RCTs were included for PFS analysis, and 4 were included for OS analysis. The median follow-up ranged from 3.1 to 7.8 years. The pooled OS HR for HDT versus SDT consolidation in patients with standard-risk and high-risk cytogenetics was 0.90 (95% confidence interval [CI], 0.70-1.17; I = 0%) and 0.66 (95% CI, 0.45-0.97; I = 0%), respectively. The difference in HDT efficacy in terms of OS between standard-risk and high-risk patients was statistically significant in favor of the high-risk group (P for interaction = .03). The pooled PFS HR for HDT versus SDT was 0.65 (95% CI 0.56-0.76; I = 0%) versus 0.52 (95% CI, 0.33-0.83; I = 55%), respectively. The difference in HDT efficacy in terms of PFS between standard-risk and high-risk patients was not significant (P for interaction = .25).

Conclusions: The magnitude of OS benefit with upfront HDT is cytogenetics-dependent. Patients with high-risk cytogenetics should preferably receive upfront rather than delayed HDT consolidation.

Lay Summary: Upfront autologous stem cell transplantation improves overall survival in patients with newly diagnosed myeloma harboring high-risk cytogenetics.