Moderate-Severe Thrombocytopenia Portends Poor Outcomes in Multiple Myeloma.

Background: Malignant plasma cells in multiple myeloma (MM) reprogram the bone marrow microenvironment to support tumor expansion. This myeloma cell-hematopoietic stem cell interaction leads to fewer hematopoietic stem cells in the bone marrow and altered differentiation of megakaryocytes, which can contribute to MM disease-related thrombocytopenia. Given the development of novel therapies for MM and the need for biomarkers reflecting the bone marrow microenvironment, we evaluated peripheral blood platelet count at diagnosis and during treatment of MM. Methods: We retrospectively evaluated 14,313 patients diagnosed with MM between 2000 and 2019 at Veterans Administration hospitals using platelet count obtained closest to diagnosis and up to 2.5 years thereafter. Patients were stratified into four categories:  moderate-severe thrombocytopenia, mild thrombocytopenia, normal platelets, and thrombocytosis (< 100, 100-149, 150-349, and ≥ 350 per microliter, respectively). Results: Thrombocytopenia, present in 25% of patients at diagnosis, corresponded to inferior overall survival (OS). During follow-up, persistent or new thrombocytopenia was also associated with inferior OS. Moreover, the negative prognostication afforded by baseline moderate-severe thrombocytopenia remained despite standard therapies (hazard ratio [HR] 1.83; 95% confidence interval [CI] 1.70-1.97) and stem cell transplant (HR 1.41; 95% CI 1.34-1.48). Conclusion: Our findings support the use of platelet count in MM as an easily accessible prognostic marker. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.