Cellular Proliferation by Multiplex Immunohistochemistry Identifies High-Risk Multiple Myeloma in Newly Diagnosed, Treatment-Naive Patients

Abstract Introduction Therapeutic options for multiple myeloma (MM) are growing, yet clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging are mainstays of risk stratification, but data suggest a complex interplay between numerous abnormalities. Myeloma cell proliferation is a metric shown to predict outcomes, but available methods are not feasible in clinical practice. Patients and Methods Multiplex immunohistochemistry (mIHC), using multiple immunostains simultaneously, is universally available for clinical use. We tested mIHC as a method to calculate a plasma cell proliferation index (PCPI). By mIHC, marrow trephine core biopsy samples were costained for CD138, a plasma cell–specific marker, and Ki-67. Myeloma cells (CD138 + ) were counted as proliferating if coexpressing Ki-67. Retrospective analysis was performed on 151 newly diagnosed, treatment-naive patients divided into 2 groups on the basis of myeloma cell proliferation: low (PCPI ≤ 5%, n = 87), and high (PCPI > 5%, n = 64). Results Median overall survival (OS) was not reached versus 78.9 months ( P  = .0434) for the low versus high PCPI groups. Multivariate analysis showed that only high-risk cytogenetics (hazard ratio [HR] = 2.02; P  = .023), International Staging System (ISS) stage > I (HR = 2.30; P  = .014), and PCPI > 5% (HR = 1.70; P  = .041) had independent effects on OS. Twenty-three (36%) of the 64 patients with low-risk disease (ISS stage 1, without high-risk cytogenetics) were uniquely reidentified as high risk by PCPI. Conclusion PCPI is a practical method that predicts OS in newly diagnosed myeloma and facilitates broader use of MM cell proliferation for risk stratification.