Baseline circulating tumor plasma cells are associated with progression-free survival in newly diagnosed multiple...

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 a single-tube 10-color next-generation flow cytometry (NGF) approach in 55 consecutive patients with symptomatic treatment-indicated NDMM. Progression-free survival (PFS) from diagnosis was analyzed using Kaplan-Meier method and compared across pragmatic CTPCs cutoffs (0.02%, 0.05%, and 0.07%) and the cohort median (0.0159%). The median follow-up by reverse Kaplan-Meier analysis was 27.9 months (interquartile range IR 20.2-31.9). The recently proposed 0.02% CTPCs threshold showed a non-significant PFS separation (median PFS 27.3 vs. 40.3 months for >0.02% vs. ≤0.02%; log-rank p=0.068; hazard ratio HR 2.23, 95% confidence interval CI 0.92-5.42). 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 14.3 vs. 40.3 months). Patients with >0.05% CTPCs were at a significantly higher risk of event (HR 3.07, 95% CI 1.29-7.31, 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, these findings support the clinical relevance of baseline CTPCs quantification in real-world NDMM, but this small single-center cohort does not formally validate any specific cutoff or establish a new clinical cutoff.