Circulating tumor cell (CTC) levels can be used to risk-stratify patients with newly diagnosed, transplant-eligible multiple myeloma (MM), according to researchers.

They found that CTC levels were an independent predictor of progression-free survival (PFS) and overall survival (OS) in this patient population. When the researchers considered CTC levels in conjunction with other prognostic factors, they were able to improve risk stratification.  

The researchers reported these findings in the Journal of Clinical Oncology.

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The study included 374 patients with newly diagnosed MM who participated in the GEM2012MENO265 and GEM2014MAIN trials ( Identifiers: NCT01916252 and NCT02406144). The researchers looked at CTCs in the peripheral blood as well as minimal residual disease (MRD) in bone marrow aspirates. 

CTCs were detected in 92% of patients (344/374). In this group, the median percentage of CTCs was 0.017% (range, 0.0002%-16%) or 1 CTC/μL (range, 0.008-1443). 

The researchers noted a “modest correlation” between CTC levels in the peripheral blood and plasma cells in the bone marrow by morphology (ρ =.41; P <.001) and flow cytometry (ρ =.46; P <.001). However, only CTC levels were an independent predictor of PFS and OS.

The percentage of plasma cells in the bone marrow was not significantly associated with PFS (hazard ratio [HR], 1.0; 95% CI, 1-1.0; P =.13) or OS (HR, 1.01; 95% CI, 1-1.0; P =.20). The percentage of CTCs in the peripheral blood was significantly associated with both PFS (HR, 1.1; 95% CI, 1-1.2; P =.01) and OS (HR, 1.14; 95% CI, 1.01-1.3; P =.03). 

The researchers also found that a CTC threshold of 0.01% was an independent predictor of PFS (HR, 2.02; 95% CI, 1.3-3.1; P =.001). The researchers noted that patients with undetectable CTC levels had “exceptional” PFS, regardless of their MRD status or whether they achieved a complete remission. For patients who had detectable CTCs, MRD negativity was associated with improved PFS.

To confirm the prognostic utility of CTCs (at 0.01% or higher), the researchers incorporated this factor into a staging system that included the following other factors: albumin less than 3.5 g/dL, β2-microglobulin greater than or equal to 5.5 mg/L, elevated lactate dehydrogenase, and high-risk cytogenetics. Each risk factor was assigned 1 point. 

Patients with higher scores were found to have worse PFS and OS. The median PFS was not reached for patients with no points, 73 months for patients with 1-2 points, and 32 months for patients with 3 or more points. 

The 5-year OS rate was 88% for patients with no points, 85% for those with 1-2 points, and 57% for patients with a score of 3 or higher. 

“Our data support the inclusion of CTCs into the list of laboratory examinations in peripheral blood at diagnosis and urge considering its utility to enhance the current stratifying systems for patients with newly diagnosed, transplant-eligible MM,” the researchers wrote.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Garcés J-J, Cedena M-T, Puig N, et al. Circulating tumor cells for the staging of patients with newly diagnosed transplant-eligible multiple myeloma. J Clin Oncol. Published online June 6, 2022. doi:10.1200/JCO.21.01365