6 research outputs found
Venetoclax plus bortezomib and dexamethasone in heavily pretreated endâstage myeloma patients without t(11;14): A realâworld cohort
P805: EXTRAMEDULLARY MULTIPLE MYELOMA: MOLECULAR PATHOGENESIS AND NOVEL THERAPEUTIC TARGETS
More than 2% of circulating tumor plasma cells defines plasma cell leukemia-like multiple myeloma
[Purpose]: Primary plasma cell leukemia (PCL) is the most aggressive monoclonal gammopathy. It was formerly characterized by 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.
[Conclusions]: 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.Supported by the European Regional Development FundâNew Directions of Biomedical Research in the Ostrava Region (No. CZ.02.1.01/0.0/0.0/18_069/0010060), by the National Institute for Cancer Research (Program EXCELES, ID Project No. LX22NPO5102)âFunded by the European UnionâNext Generation EU and by the Ministry of Health of the Czech Republic (AZVâNU21-03-00076), Institutional Support by MH CZâDROâFNOs/2019, MH CZâDROâFNOs/2020, Student's grant system SGS12/PrF/2022, SGS10/LF/2022 University of Ostrava and by the Ministry of Education, Youth and Sports of the Czech Republic through the e-INFRA CZ (ID:90140). The work was also supported by Centro de InvestigaciĂłn BiomĂ©dica en RedâĂrea de OncologĂaâdel Instituto de Salud Carlos III (CIBERONC; CB16/12/00369); Instituto de Salud Carlos III/SubdirecciĂłn General de InvestigaciĂłn Sanitaria (FIS No. PI20/00048, PI21/01816); the Cancer Research UK (C355/A26819), FCAECC and AIRC under the Accelerator Award Program (EDITOR); the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT/680200)
Clinical characteristics and outcomes in risk-stratified patients with smoldering multiple myeloma: data from the Czech Republic Registry of Monoclonal Gammopathies
Abstract Smoldering multiple myeloma (SMM) is an asymptomatic precursor to active multiple myeloma (MM). The aim of this study was to report clinical characteristics and outcomes of patients with SMM stratified based on their risk of progression to MM using the Mayo 20/2/20 criteria. Data were leveraged from the Czech Myeloma Group Registry of Monoclonal Gammopathies (RMG). Key outcomes included progression-free survival from SMM diagnosis to active MM diagnosis or death (PFS), progression-free survival from SMM diagnosis to progression on first line (1âL) MM treatment or death (PFS2), and overall survival (OS). Of 498 patients, 174 (34.9%) were classified as high risk and 324 (65.1%) as nonâhigh risk. Median follow-up was approximately 65 months. During follow-up, more patients in the high-risk vs nonâhigh-risk group received 1âL MM treatment (76.4% vs 46.6%, pâ<â0.001). PFS, PFS2, and OS were significantly shorter in high-risk vs nonâhigh-risk patients (13.2 vs 56.6 months, pâ<â0.001; 49.9 vs 84.9 months, pâ<â0.001; 93.2 vs 131.1 months, pâ=â0.012, respectively). The results of this study add to the growing body of evidence that patients with high-risk vs nonâhigh-risk SMM have significantly worse outcomes, including OS
More than 2% of circulating tumor plasma cells defines plasma cell leukemia-like multiple myeloma
PURPOSEPrimary 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.METHODSWe 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.RESULTSNewly diagnosed transplant-ineligible patients with MM with 2%-20% CTCs had significantly shorter progression-free survival (3.1 v 15.6 months; P = 2% CTCs is a biomarker of hidden primary PCL and supports the assessment of CTCs by flow cytometry during the diagnostic workup of MM