作者
Tomáš Jelı́nek,Renata Bezděková,David Žihala,Tereza Ševčíková,Anjana Anilkumar Sithara,Lenka Pospíšilová,Sabina Ševčı́ková,Petra Polackova,Martin Štork,Zdeňka Knechtová,Ondrej Venglár,Veronika Kapustová,Tereza Popková,Ludmila Muronova,Zuzana Chyra,Matouš Hrdinka,Michal Šimíček,Juan‐José Garcés,Noemí Puig,María‐Teresa Cedena,Artur Jurczyszyn,Jorge J. Castillo,Miroslav Penka,Jakub Radocha,María‐Victoria Mateos,Jesús F. San Miguel,Bruno Paiva,Luděk Pour,Lucie Říhová,Roman Hájek
摘要
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.