OBJECTIVES: Emerging therapies in MM increase OS but also prolong time to mature OS data. This research aims to critically review and evaluate potential surrogate endpoints for OS in MM and to explore if these could be used to support health technology assessments (HTAs) for new therapies when mature OS data are unavailable.

METHODS: In this SLR, Medline and Embase were searched for full-text publications including literature reviews, meta-analyses, original publications that used individual patient data (IPD) and trials that determined the correlation between surrogate endpoints and OS in MM regardless of treatment line and intervention. Selection comprised 2 reviewers. Furthermore, HTA websites from NICE, CADTH, G-BA, IQWiG, ICER, and TLV were hand-searched to assess how these HTA bodies interpreted surrogate endpoints for OS in MM.

RESULTS: Five of 51 publications analyzed a relationship between surrogate endpoints and OS. Methodologies to assess surrogacy varied: 3 of the 5 surrogacy publications used aggregated SLR data, whereas the remaining 2 used IPD. Overall, correlation was established using Spearman rank or Pearson correlation tests; predictive value was assessed using meta-regression models. Progression-free survival (PFS), time to progression, event-free survival, minimal residual disease (MRD), and duration of second-line therapy were suggested as candidates for valid surrogate endpoints for OS in MM. Most (n=46) of the identified publications evaluated the prognostic value of endpoints (e.g., treatment responses, MRD) on OS. Twenty-four appraisals from HTA bodies were identified from hand-searches discussing surrogate endpoints in MM. Generally, PFS was considered a valid surrogate marker for OS in HTA documentation. Less frequently, MRD-negative status was suggested as a surrogate endpoint for OS.

CONCLUSIONS: Data that support use of surrogate endpoints in the absence of mature OS data are available for MM. However, further validation of surrogate endpoints is required before using them in support of HTAs for new therapies.