The following is a summary of “More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma,” published in the March 2023 issue of Oncology by Jelinek, et al.

The most aggressive monoclonal gammopathy is primary plasma cell leukemia (PCL). Prior to 2021, when the criterion was lowered to ≥5%, it was previously characterized by ≥20% circulating plasma cells (CTCs). In the researchers’ hypothesis, primary PCL reflected ultra-high-risk multiple myeloma (MM), characterized by higher CTC levels rather than being a distinct clinical entity.

In order to create a criterion for CTCs that distinguished individuals with ultra-high-risk PCL-like MM, they measured the levels of CTCs by multiparameter flow cytometry in 395 patients with recently diagnosed transplant-ineligible MM. They evaluated the cutoff in 185 transplant-eligible patients with MM, and they further verified it in a separate cohort of 280 patients with MM who were treated in the GEM-CLARIDEX trial but were not transplant-eligible. For comparison of survival, the largest documented real-world cohort of patients with primary PCL was employed to compare survival. Last but not least, they questioned the existing 5% criterion for the main PCL diagnosis.

Patients with MM who had recently received a transplant but were transplanted ineligible and who had 2% to 20% CTCs had significantly worse progression-free survival (3.1 v 15.6 months; P< .001) & overall survival (14.6 v 33.6 months; P =.023) than patients with 2% CTCs. The 2% limit was successfully confirmed on an independent cohort of GEM-CLARIDEX trial patients and proven to be applicable to transplant-eligible patients with MM as well. The fact that patients with 2% to 20% CTCs had similarly poor results with primary PCL is most relevant. Also, they demonstrated that patients with 2%–5% CTCs had similar results to those with 5%–20% CTCs after demonstrating a minimal mean difference between flow cytometric & morphologic examination of CTCs.

The results of the investigation supported the evaluation of CTCs by flow cytometry during the diagnostic workup of MM since they showed that 2% CTCs were a sign of concealed primary PCL.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.01226