In a study reported in the Journal of Clinical Oncology, Jelinek et al provided evidence that a threshold of ≥ 2% circulating tumor plasma cells (CTCs) defines the presence of plasma cell leukemia (PCL)-like multiple myeloma.
As stated by the investigators, “Primary PCL is the most aggressive monoclonal gammopathy. It was formerly characterized by ≥ 20% CTCs until 2021, when this threshold was decreased to ≥ 5%. We hypothesized that primary PCL is not a separate clinical entity, but rather that it represents ultra–high-risk multiple myeloma characterized by elevated CTC levels.”
Study Details
Levels of CTCs were assessed by flow cytometry in 590 newly diagnosed patients with multiple myeloma in two Czech hematology centers between 2012 and 2019. Analysis among 395 transplant-ineligible patients was performed to identify a cutoff for CTCs identifying patients with ultra–high-risk PCL-like multiple myeloma; the cutoff was tested in 185 transplant-eligible patients in the Czech cohort and further tested in an independent cohort of 280 newly diagnosed transplant-ineligible patients treated in the GEM-CLARIDEX trial. A real-world cohort of patients with primary PCL was used for comparison of survival outcomes.
Key Points
Among the 395 transplant-ineligible patients in the Czech cohort, those with 2% to 20% CTCs (median = 4.9%; n = 15, 4%) had significantly poorer median progression-free survival (3.1 vs 15.6 months, P < .001) and overall survival (14.6 vs 33.6 months, P = .023) vs those with < 2% CTCs (median = 0.03%).
Among 185 transplant-eligible patients in the Czech cohort, those with 2% to 20% CTCs (n = 13, 7%) had significantly poorer median progression-free survival (15.4 vs 25.3 months, P < .001) and overall survival (43.1 vs 79.7 months, P = .001) vs those with < 2% CTCs. In the independent GEM-CLARIDEX cohort of 280 transplant-ineligible patients, those with 2% to 20% CTCs (n = 12, 4%) had significantly poorer median progression-free survival (11 vs 29 months, P < .001) and numerically poorer 2-year overall survival (51% vs 71%, P = .17) vs those with < 2% CTCs.
Median overall survival among 40 transplant-ineligible patients in the real-world cohort of patients with primary PCL did not differ from that among transplant-ineligible patients with 2% to 20% CTCs in the Czech cohort (13.0 vs 14.6 months, P = .908). Similar findings were made in comparison of 55 transplant-eligible patients with primary PCL with the corresponding group in the Czech cohort (median = 35.1 vs 43.1 months, P = .972).
In an analysis comparing outcomes with 2% to 5% CTCs vs 5% to 20% CTCs, transplant- ineligible patients from the Czech cohort and GEM-CLARIDEX cohort were pooled. Median progression-free survival was 3.4 months among those with 2% to 5% CTCs vs 5.1 months among those with 5% to 20% CTCs (P = .42), with both groups having significantly poorer progression-free survival vs patients with < 2% CTCs (median = 18.1 months, P < .001 for both).
The investigators concluded, “Our study uncovers that ≥ 2% CTCs is a biomarker of hidden primary PCL and supports the assessment of CTCs by flow cytometry during the diagnostic workup of multiple myeloma.”
Roman Hajek, MD, PhD, of the Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the European Regional Development Fund--New Directions of Biomedical Research in the Ostrava Region, National Institute for Cancer Research funded by the European Union, and others. For full disclosures of the study authors, visit ascopubs.org.
