Supplementary Material for: Relationship between Treatment Effects on Progression-Free Survival and Overall Survival in Multiple Myeloma: A Systematic Review and Meta-Analysis of Published Clinical Trial Data

<b><i>Background:</i></b> Demonstrating improved overall survival (OS) with new multiple myeloma (MM) treatments is becoming difficult because of extended survival, so progression-free survival (PFS) is commonly used as a surrogate endpoint for OS. We evaluated PFS as a potential surrogate for OS by examining whether observed treatment effects on PFS are positively associated with treatment effects on OS in MM. <b><i>Methods:</i></b> A systematic literature review identified 21 randomized control trials reporting hazard ratios (HRs) for treatment effects on PFS and OS. Pearson's r estimated the relationship between HRs (HR_PFS and HR_OS), and between log-transformed HRs (log(HR_PFS) and log(HR_OS)). R² values were estimated from linear regression models of the HR and the log(HR) relationships. Sensitivity and subgroup analyses examined the robustness of the HR findings. <b><i>Results:</i></b> Positive correlations were found between HR_PFS and HR_OS (r = 0.82; p &lt; 0.0001) and between log(HR_PFS) and log(HR_OS) (r = 0.80; p &lt; 0.0001). Linear regression models produced R² values of 0.67 and 0.63 when regressing HR_OS on HR_PFS, and log(HR_OS) on log(HR_PFS), respectively. Sensitivity analyses supported the HR findings. <b><i>Conclusion:</i></b> This analysis provides evidence for a positive association between treatment effects on PFS and OS. Studies involving patient level data are necessary to confirm whether PFS is a valid surrogate for OS in MM.