Primary Plasma Cell Leukemia (pPCL) is the rarest and most aggressive of the multiple myeloma variants and, typically, associated with dismal outcomes. pPCL is rated as Ultra High-Risk myeloma. It was formerly characterized by having more than 20% circulating plasma cells (CTCs) until 2021, when this threshold was decreased to having more than 5%. Circulating plasma cells are cells that are found in the blood.
An interesting article in the most recent issue of the Journal of Clinical Oncology summarizes a comprehensive study that compared treatment outcomes with varying levels of circulating plasma cells.
Key conclusions of this study are:
- Circulating plasma cells are observed in about 75% of newly diagnosed myeloma (NDMM), regardless of whether or not the patients are transplant eligible, with a median range of 0.02 – 0.03 % of total cells.
- “NDMM patients with 2%-20% of circulating plasma cells have comparable prognosis with patients with primary PCL.”
- “NDMM patients with 2%-5% of circulating plasma cells have comparable prognosis with patients with 5%-20% of circulating plasma cells.”
- “We established the threshold of 2% circulating plasma cells, which identifies patients with ultra-high-risk myeloma with practically identical prognosis as patients with pPCL.”
- “The threshold of 2% circulating plasma cells identifies a small subset (approximately 4%-7%) of NDMM with extremely poor outcomes, thus being an ideal tool for guiding therapy.”
- “The applicability of circulating plasma cells as a reliable biomarker is virtually 100% compared with cytogenetics, which is available only in 35%-50% of cases in the real-world setting, and up to 75%-90% in randomized clinical trials.”
In conclusion, the authors noted that they did not want to establish a new threshold for primary Plasma Cell Leukemia as being 2% of circulating plasma cells. Rather, they wanted to propose a new ultra-high-risk subgroup of patients with newly diagnosed multiple myeloma with an adverse prognosis. They believe that pPCL is not a separate disease, but is actually ultra-high-risk multiple myeloma.
As this type of additional testing is added to all newly diagnosed cases of multiple myeloma, measuring circulating plasma cells could identify this ultra-high-risk patient group immediately. Better diagnostics mean earlier detection and better overall care.
