In a new study, researchers characterized a subset of patients with newly diagnosed multiple myeloma (MM) with features similar to those seen with primary plasma cell leukemia (pPCL). They reported their findings in the Journal of Clinical Oncology.

In MM, tumor plasma cells can migrate to peripheral blood, and these circulating tumor cells (CTCs) can be linked to worse prognosis in newly diagnosed MM. A high degree of CTCs also characterizes pPCL, an aggressive monoclonal gammopathy currently defined as having a threshold of ≥5% CTCs. The researchers undertook this study to examine whether they could identify a subgroup of patients with ultra-high-risk PCL-like MM based on CTC level.

In determining a potential CTC threshold associated with ultra-high-risk PCL-like MM, the researchers examined survival trends in 395 patients with transplant-ineligible, newly diagnosed MM in relation to CTC levels quantified using flow cytometry. They then tested the estimated CTC threshold with data from 185 transplant-eligible patients with MM, and validated the threshold using data from 280 transplant-ineligible patients with MM from the GEM-CLARIDEX trial. ( Identifier: NCT02575144). A real-world comparator group with pPCL was also evaluated.

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The researchers found that transplant-ineligible patients with newly diagnosed MM who had CTCs in the range of 2% to 20% had a median progression-free survival (PFS) of 3.1 months, compared with 15.6 months in patients with <2% CTCs (hazard ratio [HR], 5.6; 95% CI, 3.2-10.7; P <.001). Transplant-ineligible patients with 2% to 20% CTCs also had a shorter median overall survival (OS), at 14.6 months, compared with 33.6 months for those with <2% CTCs (HR, 2.0; 95% CI, 1.1-3.7; P =.023).

Among transplant-eligible patients with newly diagnosed MM, a level of 2% to 20% CTCs was associated with a median PFS of 15.4 months, compared with 25.3 months for patients with <2% CTCs (HR, 3.8; 95% CI, 2.0-7.0; P <.001). The median OS was 43.1 months transplant-eligible patients with 2% to 20% CTCs, compared with 79.7 months among those having <2% CTCs (HR, 3.1; 95% CI, 1.5-6.4; P =.001).

In transplant-ineligible patients from the GEM-CLARIDEX trial with 2% to 20% CTCs, the median PFS was 11 months, compared with 29 months in patients with <2% CTCs (HR, 3.2; 95% CI, 1.6-6.3; P <.001). The median OS duration was also numerically shorter with patients having ≥2% CTCs, but this comparison did not reach statistical significance (HR, 1.9; P =.17).

Additional analyses showed outcomes were similar in patients having 2% to 5% CTCs compared with having 5% to 20% CTCs. The researchers also found that in patients with transplant-ineligible MM, the median OS was 14.6 months with 2% to 20% CTCs, which was similar to the median OS for the comparator group with pPCL, at 13.0 months (P =.908). Among transplant-eligible patients, median OS patterns were also similar between those with pPCL or MM and 2% to 20% CTCs.

“We established the threshold of 2% CTCs, which identifies patients with ultra-high-risk myeloma with practically identical prognosis as patients with pPCL,” the researchers wrote in their report.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Jelinek T, Bezdekova R, Zihala D, et al. More than 2% of circulating tumor plasma cells defines plasma cell leukemia–like multiple myeloma. J Clin Oncol. Published online October 31, 2022. doi:10.1200/JCO.22.01226