Baseline circulating tumor plasma cells are associated with progression-free survival in newly diagnosed multiple myeloma: a single-center real-world NGF study

Circulating tumor plasma cells (CTPCs) in peripheral blood provide a direct readout of myeloma dissemination. While CTPCs are increasingly recognized as prognostically relevant in newly diagnosed multiple myeloma (NDMM), practical cutoffs vary across cohorts and detection methods. Here, we evaluated baseline CTPCs quantified by next-generation flow cytometry (NGF) in a real-world NDMM cohort. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and compared across pragmatic CTPCs cutoffs (0.05% and 0.07%) and the cohort median (0.016%). CTPCs dichotomized at 0.05% significantly stratified PFS (log-rank p = 0.007), whereas 0.07% and the median cutoff yielded borderline separation. Patients with > 0.05% CTPCs at diagnosis showed a significantly shorter PFS compared to those with ≤ 0.05% CTPCs (median PFS of 436 vs. 1,227 days). Patients with > 0.05% CTPCs were at a significantly higher risk of event (progression or death) (hazard ratio HR 3.1, 95% confidence interval CI 1.3-7.3, p = 0.011). Peripheral blood normal plasma cells and bone marrow tumor plasma cells showed additional associations with PFS, while bone marrow normal plasma cells did not. R2-ISS stage and high-risk cytogenetics did not stratify PFS in this cohort. To conclude, baseline CTPCs measured by NGF identified a subgroup of NDMM patients at increased risk of progression in our real-world cohort. The cutoff of 0.05% should be considered pragmatic and assay-specific pending validation.