P-416: Immunophenotypic profile defines cytogenetic stability and unveils distinct prognoses in patients with newly-diagnosed multiple myeloma (NDMM)

Introduction: The prognostic significance of multiple immune antigens in patients with newly-diagnosed multiple myeloma (NDMM) has been well established. However, there is still a knowledge gap regarding the intrinsic relationship between immunophenotypes and cytogenetic stability, as well as the identification of specific immunophenotypes for precise risk stratification across different disease stages.

Methods: To address these unresolved issues, we conducted a study involving 1389 NDMM patients enrolled in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199).

Results: Our results revealed the correlation between antigen expression and cytogenetics is more prominent compared to cytopenia or organ dysfunction. Most immune antigens, except CD38, CD138, and CD81, exhibit significant associations with the incidence of at least one cytogenetic abnormality. In turn, CD38-low, CD138-low, CD27-neg, and CD28-pos expressions were associated with inferior survival outcomes (P < 0.05). Through multivariate analysis, we identified CD138-low/CD27-neg as a specific aggressive immunophenotypic profile with the highest predictive value for poor prognosis. This profile remained an independent prognostic factor on progression-free survival (HR, 1.51; P=0.003) and overall survival (HR, 1.80; P< 0.001) even in the context of cytogenetics. Importantly, CD138-low/CD27-neg profile at relapse was also associated with inferior survival after the first relapse (P < 0.001). The antigen expression profiles were not strictly similar from diagnosis to relapse, especially CD138-low/CD27-neg pattern notably increased following disease progression (19.1% to 29.1%; P=0.005).

Conclusions: In summary, we systematically described the comprehensive immunophenotypic landscapes of NDMM patients in a large observational cohort. Diverse immune profiles are strongly associated with various cytogenetic abnormalities but weakly correlated with cytopenia or organ dysfunction. Importantly, specific immunophenotypes (CD138-low/CD27-neg) could independently predict a high risk of progression or death regardless of disease stages and aggressive statuses.