Moderate-Severe Thrombocytopenia Portends Poor Outcomes in Multiple Myeloma

Malignant plasma cells in multiple myeloma (MM) reprogram the bone marrow microenvironment to support tumor expansion. In this transformative process, myeloma cells engage with hematopoietic stem cells to avoid apoptosis. The myeloma cell-hematopoietic stem cell interaction results in changes to the bone marrow microenvironment, decreased hematopoietic stem cells in the bone marrow, and suppressed differentiation of megakaryocytes, which can contribute to MM disease-related thrombocytopenia. Given the development of novel therapies for multiple myeloma and the need for prognostic markers that reflect the underlying bone marrow microenvironment, we evaluated peripheral blood platelet count at diagnosis and during treatment of MM. We retrospectively evaluated 14,425 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 4 categories: moderate-severe thrombocytopenia, mild thrombocytopenia, normal platelets, and thrombocytosis (<100, 100-149, 150-349, and ≥350 per microliter, respectively). Thrombocytopenia was present in 25% of patients at MM diagnosis and was associated with inferior overall survival (OS). Median OS of patients with moderate-severe thrombocytopenia, mild thrombocytopenia, normal platelets, and thrombocytosis at diagnosis was 1.5, 3.0, 3.7, and 2.9 years (P < .001), respectively. During treatment and follow-up, persistent or new development of thrombocytopenia was also associated with inferior OS. Moreover, the negative prognostication afforded by baseline thrombocytopenia remained despite standard therapies such as lenalidomide and bortezomib, which were associated with worse outcomes among patients with moderate-severe thrombocytopenia (hazard ratio [HR] 1.80; 95% confidence interval (CI) 1.57-2.07; P < .01) relative to those with mild thrombocytopenia (HR 1.17; 95% CI 1.06-1.29; P < .01) or thrombocytosis (HR 1.25; 95% CI 1.02-1.54; P 0.03). Our findings support the use of peripheral blood platelet count in MM as a possible surrogate for the tumor microenvironment, an easily accessible biomarker of prognosis, and a tool to guide future risk-adapted therapies.

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.