P-128: Accompanying with additional complex karyotype is a poor prognostic factor in patients with multiple myeloma with high-risk cytogenetics in the era of novel agents

Abstract

<h3>Background</h3> High-risk cytogenetic abnormality (CA) influences the prognosis of multiple myeloma (MM) even in the era of novel agents. However, prognostic heterogeneity could exist in MM patients with high-risk CA and additional cytogenetic aberrations are possibly correlated with worse outcomes. We conducted a retrospective study in patients with MM with high-risk CA to evaluate whether the outcomes are different in each high-risk group and whether the existence of additional chromosomal abnormalities would lead to poor outcomes. <h3>Method</h3> Patients with newly diagnosed MM (NDMM) in our institute between February 2006 and December 2020 were enrolled in this retrospective cohort. We analyzed only patients who were treated with novel agents including proteasome inhibitor and/or immunomodulatory drugs. All of cytogenetic abnormalities were analyzed from bone marrow samples. In this cohort, we defined high-risk CA as del(17p), t(4;14), t(14;16), and/or 1q21 gain, all of which were identified using FISH analysis. We surveyed additional chromosomal aberrations using G-banding testing. Complex chromosomal abnormality was defined as three or more chromosomal aberrations accompanying with at least one structural aberration. The survival was calculated by the Kaplan Meier method, and statistical analysis was performed by the Log-rank test. Factors affecting OS and PFS were evaluated using Cox proportional hazard model. <h3>Results</h3> We analyzed 36 MM patients who had high-risk CA at initial diagnosis. Twelve patients had del(17p), 16 had t(4;14), four had 1q21 gain, and four had more than one high-risk CA; two patients with t(4;14) and 1q21 gain, one with del(17p) and 1q21 gain and one with del(17p), t(4;14), and 1q21 gain. G-banding testing showed that patterns of complex chromosomal abnormality were found in nine patients. No significant differences in progression-free survival (PFS) and overall survival (OS) were seen between each high-risk CA group. The tendency of shorter PFS and OS was observed in patients with concurrent complex chromosomal karyotype than patients with no additional chromosomal aberrations. Furthermore, we found that the existence of complex cytogenetic abnormality by G-banding was correlated with poor PFS by multivariate analysis (hazard ratio 4.01, 95% confidence interval 1.35–11.9, p=0.012). In addition, seven of nine MM patients with complex chromosomal karyotype had concurrent plasmacytoma. <h3>Conclusion</h3> Although the limitation of retrospective study design and the small sample size exists, our findings indicate that the coexistence of complex chromosomal abnormality, probably which reflects aggressive disease status like extraosseous or extramedullary disease, could be associated with poor prognoses of MM patients with high-risk CA.