J Clin Oncol: The circulating plasma cell threshold for primary plasma cell leukemia can be reduced to 2%!

Primary plasma cell leukemia (PCL) is the most aggressive monoclonal lymphocytic malignancy
.
PCL was previously characterized by circulating plasma cells (CTCs) ≥20%, and until 2021, this threshold was reduced to ≥5%.

The researchers speculate that primary PCL is not a separate clinical entity, but rather represents an ultra-high-risk multiple myeloma (MM)
characterized by elevated CTC levels.

The researchers evaluated CTC levels in 395 newly diagnosed transplant-ineligible MM patients by multiparametric flow cytometry to determine cut-off values for CTCs, thereby identifying ultra-high-risk PCL-like MM patients
.
The researchers also examined the threshold of 185 transplant-eligible MM patients and further validated
them in an independent cohort of 280 non-transplant-eligible patients treated in the GEM-CLARDEX trial.
Survival rates
were compared using the largest published cohort of patients with primary PCL.
Finally, the researchers challenged the current 5% threshold
for the diagnosis of primary PCL.

Prognosis of patients grouped with a cut-off value of 2% CTC

Compared with CTC <2% of newly diagnosed transplant-ineligible MM patients, progression-free survival in CTC 2% to 20% of MM patients (3.
1 vs 15.
6 months; p<0.
001) and overall survival (14.
6 vs 33.
6 months; p=0.
023) is significantly shorter
.
The cut-off value of 2% was also shown to be appropriate for transplantable MM patients and was successfully validated
in an independent cohort of patients in the GEM-CLARDEX trial.
Most importantly, CTC 2%-20% of MM patients have a poor prognosis, comparable
to those with primary PCL.
In addition, after correcting for the lower mean difference between flow cytometry and CTC morphological assessment, the researchers found that the prognosis of 2%-5% of patients with CTC was similar
to that of 5%-20% of patients with CTC.

In summary, the study found that ≥2% of circulating plasma cells are biomarkers of occult primary PCL and support the identification of ultra-high-risk patients
by flow cytometry during MM diagnosis.

Original source:

Tomas Jelinek, et al.
More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma.
Journal of Clinical Oncology.
October 31, 2022.
https://ascopubs.
org/doi/full/10.
1200/JCO.
22.
01226