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Optimal Cutoff Value of Circulating Tumor Cells in Myeloma: Biomarker of Adverse Outcomes?

By: Joshua D. Madera, MS
Posted: Monday, August 22, 2022

An increasing level of circulating tumor plasma cells (CTCs) may represent an independent high-risk factor once the cells surpass an optimal cutoff value for patients with multiple myeloma, according to the multicenter, randomized, phase II FORTE study published in the Journal of Clinical Oncology. The negative prognostic impact of a cutoff of 0.07% may be further modulated by the achievement of measurable residual disease (MRD) negativity, explained Francesca Gay, MD, PhD, of the University of Torino, Italy, and colleagues.

“We believe these data can open the way to the incorporation of CTC into a wider clinical use for the routine diagnosis of patients with multiple myeloma,” the study authors suggested.

A total of 401 patients with multiple myeloma were recruited for the clinical trial. Patients were randomly assigned to receive one of three treatment regimens. Group 1 received four cycles of carfilzomib plus lenalidomide and dexamethasone (KRd), followed by melphalan at 200 mg with autologous stem cell transplantation (ASCT) and another four cycles of KRd therapy. Group 2 received four cycles of KRd therapy, three times. Group 3 received four cycles of carfilzomib plus cyclophosphamide and dexamethasone (KCd), followed by melphalan at 200 mg with ASCT and another four cycles of KCd therapy. Afterward, CTC samples were collected and analyzed using two-tube, single-platform flow cytometry. Additionally, bone marrow samples were collected and analyzed using multiparameter flow cytometry to assess MRD.

The study findings revealed an optimal CTC cutoff of 0.07% (C-index = 0.64). In addition, a moderate correlation between bone marrow plasma cells and the percentage of CTC (Pearson’s correlation coefficient = 0.38) was reported. Furthermore, patients with higher levels of CTC had significantly shorter overall survival (hazard ratio [HR] = 2.61) and progression-free survival (HR = 2.61). Moreover, the achievement of MRD negativity reduced the negative impact of high CTC levels.

Disclosure: For full disclosures of the study authors, visit

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