More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia-Like Multiple Myeloma

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Authors

JELINEK Tomas BEZDEKOVA Renata ZIHALA David SEVCIKOVA Tereza SITHARA Anjana Anilkumar POSPISILOVA Lenka ŠEVČÍKOVÁ Sabina POLACKOVA Petra ŠTORK Martin KNECHTOVÁ Zdeňka VENGLAR Ondrej KAPUSTOVA Veronika POPKOVA Tereza MURONOVA Ludmila CHYRA Zuzana HRDINKA Matous SIMICEK Michal JUAN-JOSE Garcés PUIG Noemi MARIA-TERESA Cedena JURCZYSZYN Artur CASTILLO Jorge J PENKA Miroslav RADOCHA Jakub MATEOS Maria Victoria SAN-MIGUEL Jesús F PAIVA Bruno POUR Luděk RIHOVA Lucie HAJEK Roman

Year of publication 2022
Type Article in Periodical
Magazine / Source Journal of clinical oncology
MU Faculty or unit

Faculty of Medicine

Citation
Web https://ascopubs.org/doi/full/10.1200/JCO.22.01226?af=R
Doi http://dx.doi.org/10.1200/JCO.22.01226
Attached files
Description 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 = .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.
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