The impact of high-risk cytogenetics on treatment efficacy and outcomes of patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis of randomized controlled trials.

The cytogenetic abnormalities translocations t(4;14) and t(14;16) and the deletion of chromosome 17p in newly-diagnosed multiple myeloma are associated with poor disease prognosis and are traditionally deemed as "high-risk". However, in the setting of relapsed/refractory multiple myeloma (RRMM) their effect is less characterized. A systematic search was conducted in the PubMed database (end-of-search: 20 August 2024) for randomized controlled trials on anti-myeloma therapies for RRMM that reported outcomes for standard-risk and high-risk patient subgroups. A total of 28 studies were included; 23 reported progression-free survival (PFS) and 8 overall survival (OS) outcomes. Per overall analysis, high-risk cytogenetics were not associated with impaired treatment efficacy compared to standard-risk in terms of both PFS and OS. Among 9 treatment subgroups, high-risk patients on anti-BCMA therapies seemed to exhibit a 18% lower risk of a PFS event compared to the overall treatment effect for this population, but results were not significant. In the subgroup analyses, deletion 17p seemed to have the biggest impact on treatment efficacy, but results were not statistically significant. Overall, the presence of high-risk cytogenetics at study entry in RRMM did not alter treatment efficacy. Novel tools are needed to improve risk stratification at myeloma relapse.