Circulating Tumor Cells in the Staging of Newly Diagnosed Patients With Transplant-Eligible Multiple Myeloma

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In a study reported in the Journal of Clinical Oncology, Garcés et al found that increasing levels of circulating tumor cells (CTCs) at diagnosis were associated with poorer outcomes in newly diagnosed patients with transplant-eligible multiple myeloma, and that inclusion of CTCs in a risk model may improve disease staging.

The study included data from 374 newly diagnosed patients enrolled in two clinical trials (GEM2012MENOS65 and GEM2014MAIN) who received treatment for multiple myeloma, including bortezomib, lenalidomide, and dexamethasone induction followed by autologous stem cell transplantation, consolidation, and maintenance.

Key Findings

CTCs in peripheral blood were detected on next-generation flow cytometry in 92% of patients at diagnosis. There was a modest correlation between the percentage of CTCs and plasma cells in bone marrow on morphology (ρ = 0.41) or flow cytometry (ρ = 0.46). Logarithmic increases in CTC percentage were associated with poorer progression-free survival. In multivariate analysis, increasing CTC percentage (P = .01) but not increasing plasma cells in bone marrow by morphology (P = .23) or flow cytometry (P = .13) was associated with significantly poorer progression-free survival.

A cutoff of ≥ 0.01% CTCs showed an independent prognostic value for poorer progression-free survival (hazard ratio = 2.02, 95% confidence interval = 1.3–3.1, P = .001) in multivariate analysis including International Staging System stage, lactate dehydrogenase (LDH) level, and cytogenetics.

A risk-scoring system allocating one point for each of ≥ 0.01% CTCs, low albumin, elevated β2-microglobulin, elevated LDH, and high-risk cytogenetics showed that median progression-free survival in risk group I (0 points) vs II (1 or 2 points) vs III (≥ 3 points) was not reached vs 73 months vs 32 months, respectively. P values were < .0001 overall, and < .01 for comparisons of group II and III vs I and group III vs II.

Outcomes according to percentage of CTCs and depth of response to treatment showed that 90% of patients with undetectable CTCs remained progression-free after a median follow-up of 5 years, regardless of complete remission and measurable residual disease (MRD) status. Among all patients with detectable CTCs, only achieving MRD negativity—not complete remission—was associated with significant improvement in progression-free survival.

The investigators concluded, “Evaluation of CTCs in peripheral blood outperformed quantification of bone marrow plasma cells. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible multiple myeloma.”

Bruno Paiva, PhD, of Clínica Universidad de Navarra, Pamplona, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Centro de Investigación Biomédica en Red del Instituto de Salud Carlos III, Cancer Research UK, Leukemia Lymphoma Society, and others. For full disclosures of the study authors, visit

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