Chyra, Z. (Zuzana)
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- More than 2% of circulating tumor plasma cells defines plasma cell leukemia-like multiple myeloma(2023) Venglar, O. (Ondrej); Jelinek, T. (T.); Cedena, M.T. (María Teresa); Penka, M. (Miroslav); Jurczyszyn, A. (Artur); Polackova, P. (Petra); Bezdekova, R. (R.); Pospisilova, L. (Lenka); Sevcikova, S. (Sabina); Hajek, R. (R.); Sithara, A.A. (Anjana Anikumar); Knechtova, Z. (Zdenka); Chyra, Z. (Zuzana); Mateos, M.V. (María Victoria); Popkova, T. (Tereza); Castillo, J.J. (Jorge J.); Puig, N. (Noemí); Stork, M. (Martin); Garcés-Latre, J.J. (Juan José); Zihala, D. (David); Rihova, L. (Lucie); Hrdinka, M. (Matous); Paiva, B. (Bruno); Kapustova, V. (Veronika); Muronova, L. (Ludmila); Radocha, J. (Jakub); Simicek, M. (M.); San-Miguel, J.F. (Jesús F.); Sevcikova, T. (T.); Pour, L. (Ludek)PURPOSE Primary plasma cell leukemia (PCL) is the most aggressive monoclonal gammopathy. It was formerly characterized by $ 20% circulating plasma cells (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 (MM) characterized by elevated CTC levels. METHODS We assessed the levels of CTCs by multiparameter flow cytometry in 395 patients with newly diagnosed transplant-ineligible MM to establish a cutoff for CTCs that identifies the patients with ultra-high-risk PCL-like MM. We tested the cutoff on 185 transplant-eligible patients with MM and further validated on an independent cohort of 280 transplant-ineligible patients treated in the GEM-CLARIDEX trial. The largest published real-world cohort of patients with primary PCL was used for comparison of survival. Finally, we challenged the current 5% threshold for primary PCL diagnosis. RESULTS Newly diagnosed transplant-ineligible patients with MM with 2%-20% CTCs had significantly shorter progression-free survival (3.1 v 15.6 months; P , .001) and overall survival (14.6 v 33.6 months; P 5 .023) than patients with , 2%. The 2% cutoff proved to be applicable also in transplant-eligible patients with MM and was successfully validated on an independent cohort of patients from the GEM-CLARIDEX trial. Most importantly, patients with 2%-20% CTCs had comparable dismal outcomes with primary PCL. Moreover, after revealing a low mean difference between flow cytometric and morphologic evaluation of CTCs, we showed that patients with 2%-5% CTCs have similar outcomes as those with 5%-20% CTCs. CONCLUSION 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 MM.