Scientific publications

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

Oct 31, 2022 | Magazine: Journal of Clinical Oncology

Tomas Jelinek  1 , Renata Bezdekova  2 , David Zihala  1 , Tereza Sevcikova  1   3 , Anjana Anilkumar Sithara  1   3 , Lenka Pospisilova  4 , Sabina Sevcikova  5 , Petra Polackova  2 , Martin Stork  6 , Zdenka Knechtova  6 , Ondrej Venglar  3 , Veronika Kapustova  1 , Tereza Popkova  1 , Ludmila Muronova  1 , Zuzana Chyra  1 , Matous Hrdinka  1 , Michal Simicek  1 , Juan-Jose Garcés  7 , Noemi Puig  8 , Maria-Teresa Cedena  9 , Artur Jurczyszyn  10 , Jorge J Castillo  11 , Miroslav Penka  2 , Jakub Radocha  12 , Maria Victoria Mateos  8 , Jesús F San-Miguel  7 , Bruno Paiva  7 , Ludek Pour  5 , Lucie Rihova  2 , Roman Hajek  1


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.

CITATION  J Clin Oncol. 2022 Oct 31;JCO2201226.  doi: 10.1200/JCO.22.01226

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