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

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Micro-AbstractThe plasma cell labeling index (PCLI) prognosticates survival in multiple myeloma (MM) yet is underutilized as a result of its technical difficulty. We retrospectively evaluated multiplex immunohistochemistry (mIHC) in 151 newly diagnosed patients as a clinically feasible alternative to PCLI. The mIHC correlated with PCLI results and was predictive of overall survival for MM.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.

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