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BMJ Open Jan 2024Multiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Multiple 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.
DESIGN
Systematic review and meta-analysis.
DATA SOURCE
PubMed, Web of Science, Embase and references of included studies.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
We included observational studies that evaluated the prognostic value of CPCs detected by FCM in NDMM.
DATA EXTRACTION AND SYNTHESIS
Data 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.
RESULTS
Our 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.
CONCLUSION
This 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 NUMBER
CRD42021272381.
Topics: Humans; Multiple Myeloma; Prognosis; Plasma Cells; Flow Cytometry; Hematopoietic Stem Cell Transplantation; Reproducibility of Results; Transplantation, Autologous
PubMed: 38216195
DOI: 10.1136/bmjopen-2022-071548 -
Immunity, Inflammation and Disease May 2023To review the pathogenesis and treatment of multiple myeloma (MM). MM is a hematological malignancy with abnormal plasma cell proliferation in bone marrow. Due to the...
INTRODUCTION
To review the pathogenesis and treatment of multiple myeloma (MM). MM is a hematological malignancy with abnormal plasma cell proliferation in bone marrow. Due to the emergence of drug resistance, MM is still an incurable malignancy, which requires further exploration of pathogenesis and effective therapeutic targets.
METHODS
In this paper, the method of literature review is adopted to obtain the information about MM. Based on the literature, comprehensive and systematic review is made.
RESULTS
MM is a complex pathophysiological process with great heterogeneity, mainly reflected in genomic instability and bone marrow microenvironment. At present, the treatment of MM has made great progress, proteasome inhibitors and immunomodulatory drugs are widely used in clinic. Allogeneic stem cell transplantation may be the only promising cure for MM, and its high transplant-related mortality limits its clinical application.
CONCLUSIONS
The future of MM treatment lies in the development of more targeted therapies, novel immunotherapies, and a better understanding of the disease's molecular and genetic basis.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Immunotherapy; Multiple Myeloma; Tumor Microenvironment
PubMed: 37249283
DOI: 10.1002/iid3.850 -
Journal of Geriatric Oncology Nov 2020Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic cell transplantation (tiMM). We aimed to identify treatment options that provide the best balance in terms of efficacy and safety.
METHODS
We searched bibliographic databases and meeting libraries for search terms reflecting newly diagnosed and older and/or transplant-ineligible patients from inception to October 21, 2018. Phase II/III randomized trials comparing at least two first line treatment regimens for newly diagnosed tiMM were included. We extracted data on efficacy (progression free survival, PFS, overall survival and overall response rate) and safety (grade ¾ toxicities) and conducted network meta-analysis using Bayesian methods and random effects models. Relative ranking of treatment regimens was assessed using Surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
We identified 27 trials involving 12,194 patients. For PFS, the four most effective regimens were: Daratumumab, Bortezomib, Melphalan and Prednisone (SUCRA 0.960) followed by Daratumumab, lenalidomide and dexamethasone (Dara_RD, SUCRA 0.847), Bortezomib, melphalan, prednisone, thalidomide maintenance with bortezomib-thalidomide (SUCRA 0.834) and Bortezomib, Lenalidomide and Dexamethasone (SUCRA 0.739). Among these four most efficacious regimens, toxicity profile was most favorable for Dara_RD (median additional AEs per patient vs dexamethasone = 0.74; 95% CrI 0.51-1.17; SUCRA 0.430).
CONCLUSION
Among first line tiMM regimens, increasing efficacy is associated with increased toxicity. We provide relative ranking of these regimens for both efficacy and safety. Future studies should incorporate geriatric assessments and frailty biomarkers to refine treatment decision-making for each individual patient.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Humans; Lenalidomide; Multiple Myeloma; Treatment Outcome
PubMed: 32513568
DOI: 10.1016/j.jgo.2020.05.013 -
Technology in Cancer Research &... 2022Cyclin D1 has been identified as a proto-oncogene associated with the uncontrolled proliferation of tumor cells. This systematic review and meta-analysis aims to... (Meta-Analysis)
Meta-Analysis
Cyclin D1 has been identified as a proto-oncogene associated with the uncontrolled proliferation of tumor cells. This systematic review and meta-analysis aims to estimate the prognostic significance of cyclin D1 in multiple myeloma (MM) patients. We searched for qualified data in PubMed, Embase, and Web of Science up to February 2020. Data quality was assessed by the Newcastle-Ottawa scale (NOS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to evaluate the relationship between cyclin D1 expression and overall survival (OS), progression-free survival (PFS)/event-free survival (EFS) in patients with MM. A total of 13 studies involving 961 patients were included. Overall, pooled analysis revealed significant heterogeneity between cyclin D1 expression and the prognosis of MM (OS, HR = 1.08, 95% CI: 0.71-1.64, = 67.9%; PFS/EFS, HR = 0.97, 95% CI: 0.49-1.93, = 85.8%). Subgroup analysis revealed that the prolongation of OS was relevant to increased expression of cyclin D1 in MM patients in the relapsed and refractory group (OS, HR = 0.46, 95% CI: 0.24-0.90). Another subgroup assessment of OS established that MM patients with overexpression in the bortezomib group had longer survival time (HR = 0.30, 95% CI: 0.11-0.82), whereas, those overexpressing in the conventional chemotherapy group had poor prognosis (HR = 2.19, 95% CI: 1.18-4.08). We also found that increased cyclin D1 expression correlated favorably with PFS in the autologous stem cell transplantation (ASCT) (HR = 0.45, 95% CI: 0.28-0.73) or reverse transcription-polymerase chain reaction (RT-PCR) group (HR = 0.41, 95% CI: 0.26-0.64). The result of this meta-analysis suggested that overexpression might be a predictive biomarker for MM patients when treated with bortezomib, receiving ASCT, or in relapsed and refractory period.
Topics: Biomarkers, Tumor; Cyclin D1; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Multiple Myeloma; Polymerase Chain Reaction; Prognosis; Publication Bias; Survival Analysis
PubMed: 35098809
DOI: 10.1177/15330338211065252 -
JCO Global Oncology Aug 2022The globalization of clinical trials has accelerated recent advances in multiple myeloma (MM). However, it is unclear whether trial enrollment locations are reflective...
PURPOSE
The globalization of clinical trials has accelerated recent advances in multiple myeloma (MM). However, it is unclear whether trial enrollment locations are reflective of the global burden of MM and whether access to novel therapies is timely and equitable for countries that participate in those trials.
METHODS
To assess this, we characterized where MM trials that led to US Food and Drug Administration (FDA) approvals were conducted and determined how often and quickly these drug regimens received approval in their participating trial countries on the basis of country income level and geographic region.
RESULTS
A systematic review was conducted to identify all MM clinical trials that met their primary endpoint, enrolled patients outside the United States, and resulted in FDA approval from 2005 to 2019. A total of 18 pivotal MM clinical trials were identified. High-income countries enrolled patients in 100% (18/18) of the trials identified, whereas upper-middle and lower-middle-income countries were represented in 61% (11/18) and 28% (5/18) of trials, respectively. No patients from low-income countries were enrolled. One trial enrolled patients in sub-Saharan Africa, and no trials enrolled patients in South Asia/Caribbean. For drugs/regimens that were approved in their participating countries, the median time from FDA approval to approval was 10.9 months. There were no drugs approved in lower-middle-income trial countries. MM trials leading to FDA approval are generally run in high-income, European, and Central Asian countries.
CONCLUSION
There are substantial disparities in where novel therapies are evaluated and where they are ultimately approved for use on the basis of income level and geography.
Topics: Drug Approval; Ethnicity; Humans; Multiple Myeloma; Pharmaceutical Preparations; United States; United States Food and Drug Administration
PubMed: 35960904
DOI: 10.1200/GO.22.00119 -
ESC Heart Failure Oct 2019The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and... (Comparative Study)
Comparative Study Meta-Analysis
AIMS
The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis.
METHODS AND RESULTS
MEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light-chain (AL) amyloidosis. In this meta-analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra-cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta-analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1-99.0% and specificity 11.0-60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS-2 was generally poor with evidence of bias.
CONCLUSIONS
Cardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non-invasive diagnostic algorithm that also tests for the presence of monoclonal protein.
Topics: Amyloid Neuropathies, Familial; Amyloidosis; Biopsy; Diagnosis, Differential; Heart Diseases; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Prevalence; Radionuclide Imaging; Sensitivity and Specificity
PubMed: 31487121
DOI: 10.1002/ehf2.12511 -
The Journal of International Medical... Aug 2021To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM).
METHODS
A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab.
RESULTS
A total of seven RCTs were included ( = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group.
CONCLUSION
The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Humans; Multiple Myeloma; Neutropenia
PubMed: 34433331
DOI: 10.1177/03000605211038135 -
Discovery Medicine Oct 2016Recently, carfilzomib has become a promising therapeutic approach for relapsed and (or) refractory multiple myeloma (RRMM), but no study has summarized the overall... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Recently, carfilzomib has become a promising therapeutic approach for relapsed and (or) refractory multiple myeloma (RRMM), but no study has summarized the overall effect of carfilzomib in RRMM. To explore the role of carfilzomib, we performed a meta-analysis of all known prospective clinical trials to assess the efficacy of carfilzomib in patients with RRMM.
METHODS AND MATERIALS
A systematic review of publications was performed on December 15, 2015. Eight studies including 1,446 patients were identified. Meta-analyses were carried out to calculate the overall response rate (ORR), complete response rate (CRR), and clinical benefit rate (CBR) of carfilzomib for RRMM.
RESULTS
In patients with RRMM, ORR was 0.44, CRR was 0.13, and CBR was 0.54. High heterogeneity between studies was observed, and funnel plots were symmetrical, negating publication bias. Carfilzomib was generally well tolerated by patients reported in the studies though some manageable adverse effects occurred.
CONCLUSION
Our analysis revealed a promising benefit of carfilzomib in the treatment of RRMM.
Topics: Clinical Trials as Topic; Multiple Myeloma; Neoplasm Recurrence, Local; Oligopeptides
PubMed: 27875670
DOI: No ID Found -
Journal of Medical Economics 2023The goal of this study was to review the economic evaluations of health technologies in multiple myeloma (MM) and provide guidance and recommendations for future health...
AIMS
The goal of this study was to review the economic evaluations of health technologies in multiple myeloma (MM) and provide guidance and recommendations for future health economic analyses.
MATERIALS AND METHODS
A systemic literature review (SLR) was conducted on original economic assessment studies and structured review papers focusing on the studies in MM. The search was limited to English language papers published from 1 January 2000 onwards. Publications not applying any type of modelling methodology to describe disease progression and patient pathways over a specific time horizon were excluded.
RESULTS
A total of 2,643 publications were initially identified, of which 148 were eligible to be included in the full-text review phase. From these, 49 publications were included in the final analysis. Most published health economic analyses supported by models came from high-income countries. Evaluations from middle-income countries were rarely published. Diagnostic technologies were rarely modelled and integrated care had not been modelled. Very few models investigated MM treatments from a societal perspective and there was a relative lack of evaluations regarding minimal residual disease (MRD).
LIMITATIONS
Limitations of the publications included differences between trial populations and modelled populations, justification of methods, lack of confounder analyses, and small trial populations. Limitations of our study included the infeasibility of comparing MM economic evaluations due to the significant variance in modelled therapeutic lines and indications, and the relative scarcity of published economic evaluations from non-high-income countries.
CONCLUSIONS
As published economic models lacked many of the elements of the complex and heterogeneous patient pathways in MM and they focused on single decision problems, a thorough, open-source economic whole disease modelling framework is needed to assess the economic value of a wide range of technologies across countries with various income levels with a more detailed view on MM, by including patient-centric and societal aspects.
Topics: Humans; Multiple Myeloma; Models, Economic; Cost-Benefit Analysis
PubMed: 36346000
DOI: 10.1080/13696998.2022.2144056 -
Blood Cancer Journal Jan 2023Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging...
Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score (39.5%). Frailty status was categorized with 3 levels as (frail, intermediate fit, or fit) in 51.2% of the studies and dichotomized (frail, non-frail) in 18.6% of studies. Frailty prevalence greatly varied across trials ranging from 17.2% to 73.6% of the cohort. Of the included studies, 72.0% conducted subgroup analysis (planned or post-hoc) based on frailty status. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes.
Topics: Humans; Aged; Frail Elderly; Frailty; Multiple Myeloma; Prevalence; Hematologic Neoplasms
PubMed: 36599867
DOI: 10.1038/s41408-022-00779-2