Development of Novel Peripheral Blood Count-Based Prognostic Index for Multiple Myeloma

In multiple myeloma (MM), clonal plasma cells evade immune surveillance and proliferate within an inflammatory bone marrow microenvironment. During pathogenesis, monocyte-derived tumor-associated macrophages help myeloma cells to avoid apoptosis; effector T cell lymphocytes undergo senescence to enable preferential upregulation of their immunosuppressive regulatory T cell counterparts; and myeloma cells interact with hematopoietic stem cells to inhibit downstream megakaryocyte differentiation into platelets.¹ Our prior research has suggested a prognostic role for the absolute monocyte count (AMC), absolute lymphocyte count (ALC), and platelet count as biomarkers. We have shown that abnormal AMC and decreased ALC and platelet count are associated with decreased overall survival (OS) among patients with MM at diagnosis and follow-up. Based on the easy accessibility of these peripheral blood markers and need for dynamic prognostication among patients with MM undergoing novel therapies, we created a categorical peripheral blood-based prognostic index for MM incorporating AMC, ALC and platelet count. We retrospectively evaluated this index in 10790 patients diagnosed with MM between 2000 and 2019 at Veterans Administration hospitals using cell counts obtained closest to diagnosis and up to 2.5 years thereafter. Patients were stratified into 3 levels based on a logarithmic risk score, where those with the lowest counts across all cell lines (AMC, ALC, and platelet count) were in level III and those with counts approaching normalcy were in level I. At diagnosis, 8% of patients were in level III and had the highest risk of death (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.85-2.24; P < .01) compared to those in levels I (HR 1.15; 95% CI, 1.08-1.23; P < .01) and II (HR 1.37; 95% CI, 1.28-1.46; P < .01). Moreover, the risk of inferior OS associated with level III status persisted during treatment and follow-up and existed independently of other known risk stratification tools (including Charlson comorbidity index, lactate dehydrogenase, International Staging System classification). With further validation, our findings support the use of our novel prognostic index, which potentially reflects the underlying tumor microenvironment, as an available tool for risk stratification during the MM disease course.

Munshi:AbbVie, Adaptive Bio, Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Legend Bio, Novartis, Oncopep, Pfizer, Recordati, Sebia, Takeda: Consultancy; Oncopep: Current holder of stock options in a privately-held company.