Expression of Concern: Prognostic value of circulating plasma cells in patients with multiple myeloma: A meta-analysis
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PROVIDER: S-EPMC9942954 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:PurposeThe clinical significance and prognostic role of circulating plasma cells (CPCs) in multiple myeloma (MM) are still controversial. We conducted the first meta-analysis to clarify the correlation between CPCs and the clinicopathological features and prognosis of MM patients.MethodsA comprehensive literary search for relevant studies was performed on PubMed, Embase, Medline, CNKI (Chinese) and Web of Science databases (January 1, 1950 to December 20, 2016). The associations between CPCs and survival rate and clinicopathological parameters, including International staging system (ISS) and Durie-Salm staging system (DS) stage, were evaluated. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analysis, sensitivity analysis, and publication bias were conducted.Results11 studies covering a total of 2943 patients were included. Pooled hazard ratios (HRs) revealed that the presence of CPCs predicted aggressive disease progression (HR = 1.78, 95% CI = 1.57-2.03) and reduced overall survival (OS) (HR = 1.82, 95% CI = 1.59-2.08). Subgroup analyses demonstrated that CPCs positive patients also had poor disease progression and OS in detection methods and sampling time subsets. Moreover, the presence of CPCs was strikingly associated with increased ISS stage (OR = 2.78% CI = 1.69-4.56), but not with DS stage(OR = 1.60; 95% CI = 0.74-3.47).ConclusionsCPCs status is associated with poorer survival outcome in multiple myeloma. Additionally, increased ISS stage could be significant risk factors for the presence of CPCs.
| S-EPMC5509371 | biostudies-literature
Project description:ObjectivesMultiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on cytogenetic and clinical biomarkers. The circulating clonal plasma cells (CPCs) were reported to have potential prognostic impact on MM. Among various diagnostic approaches, multiparametric flow cytometry (FCM) offers heightened sensitivity, minimal invasiveness and reproducibility. We conducted a meta-analysis to evaluate the prognostic value of quantifying CPCs via FCM in newly diagnosed symptomatic MM (NDMM) patients.DesignSystematic review and meta-analysis.Data sourcePubMed, Web of Science, Embase and references of included studies.Eligibility criteria for selecting studiesWe included observational studies that evaluated the prognostic value of CPCs detected by FCM in NDMM.Data extraction and synthesisData were screened and extracted independently by two investigators. The pooled results originated from random effects models. The primary endpoint was overall survival (OS). The secondary endpoint was progression-free survival (PFS). To evaluate the prognostic value of CPCs in NDMM, HRs and their 95% CI for both OS and PFS were derived using COX multivariable models. These values were then used to compute the pooled estimated effect.ResultsOur meta-analysis encompassed a total of 2704 NDMM patients from 11 studies up to 27 August 2022. The pooled HR for OS and PFS in CPC-positive (CPCs+) group and CPC-negative group were 1.95 (95% CI 1.24 to 3.07) and 2.07 (95% CI 1.79 to 2.39), respectively. The autologous stem cell transplantation (ASCT) failed to eliminate the adverse impact on OS and PFS. The heterogeneity may stem from the use of novel agents or traditional chemotherapy as initial treatment.ConclusionThis meta-analysis indicates CPCs+ had an adverse impact on the prognosis of NDMM patients in the total population, and the adverse impact could not be eliminated by ASCT.Prospero registration numberCRD42021272381.
| S-EPMC10810043 | biostudies-literature
Project description:The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6-9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×109/L vs 214×109/L, P<0.0001) and higher bone marrow plasma cells (median 53% vs 36%, P=0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia.
| S-EPMC5451342 | biostudies-literature
Project description:Background: To investigate the prognostic value of circulating plasma cells (CPC) and establish novel nomograms to predict individual progression-free survival (PFS) as well as overall survival (OS) of patients with newly diagnosed multiple myeloma (NDMM). Methods: One hundred ninetyone NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8 were included in the study. The entire cohort was randomly divided into a training (n = 130) and a validation cohort (n = 61). Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes, and the nomograms were validated by calibration curves. Results: When the cut-off value was 0.038%, CPC could well distinguish patients with higher tumor burden and lower response rates (P < 0.05), and could be used as an independent predictor of PFS and OS. Nomograms predicting PFS and OS were developed according to CPC, lactate dehydrogenase (LDH) and creatinine. The C-index and the area under receiver operating characteristic curves (AUC) of the nomograms showed excellent individually predictive effects in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤ 60.7 for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group. The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group (p < 0.001). Conclusions: CPC is an independent prognostic factor for NDMM patients. The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.
| S-EPMC7973368 | biostudies-literature
Project description:While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1, cMAF and MAFb proteins in plasma cells isolated from the bone marrow of 39 MM patients treated with bortezomib-based regimens using an enzyme-linked immunosorbent assay (ELISA). The proteins were selected on the basis of previous laboratory and clinical studies in bortezomib-treated MM patients. It was found that the expression of the investigated proteins did not significantly differ between bortezomib-sensitive and bortezomib-refractory patients. However, the expression of some proteins correlated with overall survival (OS); this was significantly shorter in patients with higher POMP expression (HR 2.8, 95% CI: 1.1-7.0, p = 0.0277) and longer in those with higher MAFB expression (HR 0.32, 95% CI: 0.13-0.80, p = 0.0147). Our results indicate that a high expression of POMP and MAFB in MM plasma cells may serve as predictors of OS in MM patients treated with bortezomib-based regimens. However, further studies are needed to determine the role of these factors in effective strategies for improving anti-myeloma therapy.
| S-EPMC8584776 | biostudies-literature
Project description:In recent years, liquid biopsy has emerged as a promising alternative to the bone marrow (BM) examination, since it is a minimally invasive technique allowing serial monitoring. Circulating multiple myeloma cells (CMMCs) enumerated using CELLSEARCH® were correlated with patients' prognosis and measured under treatment to assess their role in monitoring disease dynamics. Forty-four MM and seven smouldering MM (SMM) patients were studied. The CMMC medians at diagnosis were 349 (1 to 39,940) and 327 (range 22-2463) for MM and SMM, respectively. In the MM patients, the CMMC count was correlated with serum albumin, calcium, β2-microglobulin, and monoclonal components (p < 0.04). Under therapy, the CMMCs were consistently detectable in 15/40 patients (coMMstant = 1) and were undetectable or decreasing in 25/40 patients (coMMstant = 0). High-quality response rates were lower in the coMMstant = 1 group (p = 0.04), with a 7.8-fold higher risk of death (p = 0.039), suggesting that continuous CMMC release is correlated with poor responses. In four MM patients, a single-cell DNA sequencing analysis on residual CMMCs confirmed the genomic pattern of the aberrations observed in the BM samples, also highlighting the presence of emerging clones. The CMMC kinetics during treatment were used to separate the patients into two subgroups based on the coMMstant index, with different responses and survival probabilities, providing evidence that CMMC persistence is associated with a poor disease course.
| S-EPMC11393854 | biostudies-literature
Project description:BackgroundCirculating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.MethodsThe PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software.ResultsTwenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001).ConclusionOur meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.
| S-EPMC11008311 | biostudies-literature
Project description: Not available
| S-EPMC10036560 | biostudies-literature
Project description: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 < .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.ConclusionOur 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.
| S-EPMC9995102 | biostudies-literature
Project description:IntroductionCirculating plasma cells (CPC) have been reported to be one of the indicators of high-risk multiple myeloma (MM), yet the prognostic significance of CPC in Chinese population and the genetic mechanisms underlying CPC formation have not been fully elucidated.MethodsPatients with newly diagnosed MM were included in this study. We used multi-parameter flow cytometry (MFC) for CPC quantification and next-generation sequencing (NGS) technology for mutational landscape mapping to identify the correlation of CPC level with clinical characteristics and the mutations.ResultsA total of 301 patients were enrolled in this investigation. We demonstrated that CPC quantification could effectively mirror the tumor load, and CPC ≥ 0.105% at diagnosis or detectable CPC after therapy indicates poor treatment response and adverse outcome, and the introduction of CPC into the R-ISS enables a more accurate risk stratification. Interestingly, we noticed an elevated percentage of light-chain MM in patients with higher CPC. Mutational landscape revealed that patients harboring mutations in TP53, BRAF, DNMT3A, TENT5C, and IL-6/JAK/STAT3 pathway-related genes tended to have higher CPC levels. Gene enrichment analysis demonstrated that pathways involving chromosome regulation and adhesion may be potential mechanisms accounting for CPC formation.DiscussionAccordingly, quantification of CPC may provide a less-invasive and reliable approach for identifying high-risk MM in Chinese population.
| S-EPMC9947848 | biostudies-literature