A comprehensive analysis of bone marrow-derived cytogenetic abnormalities in multiple myeloma patients with extramedullary disease.

Background: Extramedullary disease (EMD) in multiple myeloma (MM) remains a critical clinical challenge due to its aggressive behavior and resistance to conventional therapies. While cytogenetic abnormalities are recognized contributors to MM progression, their specific roles in EMD pathogenesis-particularly in distinguishing bone marrowderived profiles between EMD and non-EMD patients-remain inadequately characterized.

Methods: In this comprehensive study, we analyzed 41 published studies involving 9424 MM patients, and identified EMD in 32.2% (3038) of cases. Our aim was to elucidate the bone marrow-derived cytogenetic profiles of MM patients with EMD, comparing them to those without EMD.

Results: Among EMD-MM patients, the most prevalent abnormalities were del(13q)/del RB1 (32.3%), 1q21+ (29.6%), and hyperdiploidy (26.3%). High-risk cytogenetic abnormalities were led by 1q21+ (29.6%), del(17p)/del p53 (14.4%), and t(4;14) (13.6%). Notably, 1q21+ was the most frequent aberration in the EM-E subgroup, accounting for 32.2% of cases. Comparative analyses revealed significantly higher frequencies of del(17p)/del p53 and del(13q)/del RB1 in EMD patients compared to non-EMD patients, along with a slightly higher frequency of 1q21+. Conversely, EMD patients exhibited lower frequencies of hyperdiploidy and t(11;14) promoting MM evolution. Subgroup analyses confirmed these trends and revealed a more pronounced prevalence of del(13q)/del RB1 in the EM-E subgroup.

Conclusions: Our findings underscore the importance of integrating cytogenetic data into risk stratification for MM patients with EMD. These results also highlight the need for further research to elucidate the mechanisms underlying cytogenetic abnormalities in EMD and their clinical implications.