High-Risk Cytogenetic Multiple Myeloma Remains a Therapeutic Challenge: A 15-Year Real-World Analysis

Background: High-risk cytogenetic multiple myeloma (HRMM) confers inferior outcomes despite significant therapeutic advances. Real-world data characterizing contemporary treatment patterns across lines of therapy in this population are limited. Methods: We conducted a multicenter retrospective study of 205 patients with HRMM diagnosed between January 2009 and January 2024. High-risk cytogenetics were defined according to the International Myeloma Working Group (IMWG) and Revised International Staging System (R-ISS) criteria as the presence of del(17p), t(4;14), t(14;16), t(14;20), and/or gain/amplification of 1q21. Treatment regimens were categorized by the number of agents (doublet, triplet, quadruplet), mechanism of action (proteasome inhibitor [PI]-based, immunomodulatory drug [IMiD]-based, and anti-CD38 monoclonal antibody-based), and specific regimen composition. Treatment patterns were analyzed across three treatment eras and stratified by age (