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More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma
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 repres...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995102/ https://www.ncbi.nlm.nih.gov/pubmed/36315921 http://dx.doi.org/10.1200/JCO.22.01226 |
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author | Jelinek, Tomas Bezdekova, Renata Zihala, David Sevcikova, Tereza Anilkumar Sithara, Anjana Pospisilova, Lenka Sevcikova, Sabina Polackova, Petra Stork, Martin Knechtova, Zdenka Venglar, Ondrej Kapustova, Veronika Popkova, Tereza Muronova, Ludmila Chyra, Zuzana Hrdinka, Matous Simicek, Michal Garcés, Juan-Jose Puig, Noemi Cedena, Maria-Teresa Jurczyszyn, Artur Castillo, Jorge J. Penka, Miroslav Radocha, Jakub Mateos, Maria Victoria San-Miguel, Jesús F. Paiva, Bruno Pour, Ludek Rihova, Lucie Hajek, Roman |
author_facet | Jelinek, Tomas Bezdekova, Renata Zihala, David Sevcikova, Tereza Anilkumar Sithara, Anjana Pospisilova, Lenka Sevcikova, Sabina Polackova, Petra Stork, Martin Knechtova, Zdenka Venglar, Ondrej Kapustova, Veronika Popkova, Tereza Muronova, Ludmila Chyra, Zuzana Hrdinka, Matous Simicek, Michal Garcés, Juan-Jose Puig, Noemi Cedena, Maria-Teresa Jurczyszyn, Artur Castillo, Jorge J. Penka, Miroslav Radocha, Jakub Mateos, Maria Victoria San-Miguel, Jesús F. Paiva, Bruno Pour, Ludek Rihova, Lucie Hajek, Roman |
author_sort | Jelinek, Tomas |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9995102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
spelling | pubmed-99951022023-03-09 More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma Jelinek, Tomas Bezdekova, Renata Zihala, David Sevcikova, Tereza Anilkumar Sithara, Anjana Pospisilova, Lenka Sevcikova, Sabina Polackova, Petra Stork, Martin Knechtova, Zdenka Venglar, Ondrej Kapustova, Veronika Popkova, Tereza Muronova, Ludmila Chyra, Zuzana Hrdinka, Matous Simicek, Michal Garcés, Juan-Jose Puig, Noemi Cedena, Maria-Teresa Jurczyszyn, Artur Castillo, Jorge J. Penka, Miroslav Radocha, Jakub Mateos, Maria Victoria San-Miguel, Jesús F. Paiva, Bruno Pour, Ludek Rihova, Lucie Hajek, Roman J Clin Oncol ORIGINAL REPORTS 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. Wolters Kluwer Health 2023-03-01 2022-10-31 /pmc/articles/PMC9995102/ /pubmed/36315921 http://dx.doi.org/10.1200/JCO.22.01226 Text en © 2022 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | ORIGINAL REPORTS Jelinek, Tomas Bezdekova, Renata Zihala, David Sevcikova, Tereza Anilkumar Sithara, Anjana Pospisilova, Lenka Sevcikova, Sabina Polackova, Petra Stork, Martin Knechtova, Zdenka Venglar, Ondrej Kapustova, Veronika Popkova, Tereza Muronova, Ludmila Chyra, Zuzana Hrdinka, Matous Simicek, Michal Garcés, Juan-Jose Puig, Noemi Cedena, Maria-Teresa Jurczyszyn, Artur Castillo, Jorge J. Penka, Miroslav Radocha, Jakub Mateos, Maria Victoria San-Miguel, Jesús F. Paiva, Bruno Pour, Ludek Rihova, Lucie Hajek, Roman More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma |
title | More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma |
title_full | More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma |
title_fullStr | More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma |
title_full_unstemmed | More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma |
title_short | More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia–Like Multiple Myeloma |
title_sort | more than 2% of circulating tumor plasma cells defines plasma cell leukemia–like multiple myeloma |
topic | ORIGINAL REPORTS |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995102/ https://www.ncbi.nlm.nih.gov/pubmed/36315921 http://dx.doi.org/10.1200/JCO.22.01226 |
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