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International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
Frontiers in Oncology 2023The current study aims to evaluate the safety and efficacy of anti-CD38 monoclonal antibodies (mAbs) among patients with relapsed/refractory multiple myeloma (RRMM)...
Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.
OBJECTIVES
The current study aims to evaluate the safety and efficacy of anti-CD38 monoclonal antibodies (mAbs) among patients with relapsed/refractory multiple myeloma (RRMM) through meta-analysis.
METHODS
As of June 2023, we searched PubMed, Web of Science, Embase and the Cochrane Library. Randomized controlled trials (RCTs) which compared the clinical outcomes of anti-CD38 mAbs plus immunomodulatory drugs (IMiDs) or proteasome inhibitors (PIs) plus dexamethasone and IMiDs (or PIs) and dexamethasone alone for RRMM patients were included. Efficacy outcomes were mainly evaluated with progression-free survival (PFS) and overall survival (OS). The safety was analyzed with hematologic and nonhematologic treatment-emergent adverse events (TEAEs). All results were pooled using hazard ratio (HR), relative risk (RR), and their 95% confidence interval (CI) and prediction interval (PI).
RESULTS
This meta-analysis included 11 RCTs in total. Compared with IMiDs (or PIs) and dexamethasone alone, anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone significantly prolonged PFS (HR: 0.552, 95% CI = 0.461 to 0.659, 95% PI = 0.318 to 0.957) and OS (HR: 0.737, 95% CI = 0.657 to 0.827, 95% PI = 0.626 to 0.868) in patients with RRMM. Additionally, RRMM patients receiving anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone achieved higher rates of overall response (RR: 1.281, 95% CI = 1.144 to 1.434, 95% PI = 0.883 to 1.859), complete response or better (RR: 2.602, 95% CI = 1.977 to 3.424, 95% PI = 1.203 to 5.628), very good partial response (VGPR) or better (RR: 1.886, 95% CI = 1.532 to 2.322, 95% PI = 0.953 to 3.731), and minimum residual disease (MRD)-negative (RR: 4.147, 95% CI = 2.588 to 6.644, 95% PI = 1.056 to 16.283) than those receiving IMiDs (or PIs) and dexamethasone alone. For TEAEs, the rates of hematologic and nonhematologic TEAEs, including thrombocytopenia, neutropenia, upper respiratory tract infection (URTI), pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension, were higher in the anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone group than in the IMiDs (or PIs) and dexamethasone group.
CONCLUSION
Our study showed that anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone improved PFS and OS, and achieved higher rates of overall response, complete response or better, VGPR or better, and MRD-negative, as well as higher rates of thrombocytopenia, neutropenia, URTI, pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension in RRMM patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431071.
PubMed: 38144527
DOI: 10.3389/fonc.2023.1240318 -
International Journal of Molecular... May 2024Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell)... (Meta-Analysis)
Meta-Analysis Review
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Topics: Multiple Myeloma; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Treatment Outcome; Quality of Life; Neoplasm Recurrence, Local; Cytokine Release Syndrome
PubMed: 38732213
DOI: 10.3390/ijms25094996 -
European Review For Medical and... Nov 2022Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of triplet regimens based on pomalidomide and dexamethasone for treatment of relapsed/refractory multiple myeloma: a systematic review and meta-analysis.
OBJECTIVE
Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very clear. This meta-analysis aimed at comparing the safety and efficacy of different triplet therapies and analyzing the best therapy regimen.
MATERIALS AND METHODS
A comprehensive literature search identified a total of 615 studies, and 22 studies assessing 1,889 subjects met the inclusion criteria of this meta: phase II/III trial, over 2 median lines of prior therapy, and detailed efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival (PFS). All statistical analyses were performed by Revman version 5.3, and the heterogeneity was tested by I2 (25% indicating low heterogeneity, 50% moderate, and 75% high). For those with less heterogeneity, fixed-effect model was used. With a significant high heterogeneity, a random-effect model was used.
RESULTS
Pooled analysis showed ORR 66.2% across all triplet regimens based on pomalidomide and dexamethasone. Among all triplet regimens, therapy containing bortezomib showed the highest ORR (90.3%), and the one containing elotuzumab showed the lowest ORR (41.2%). The pooled ORRs for the remaining treatment regimens are as follows: cyclophosphamide (70.1%), isatuximab (66.3%), daratumumab (61.2%), clarithromycin (60.0%), pembrolizumab (47.3%). A total of 21 adverse events appeared in the included studies, with neutropenia being the highest incidence of hematologic adverse events (32.1%) and cough being the highest incidence of non-hematologic adverse events (43.3.%).
CONCLUSIONS
Three-drug regimens based on pomalidomide and dexamethasone could yield excellent overall response rate to relapsed/refractory multiple myeloma, but there are still various adverse events; therefore, consequent studies should address these adverse events.
Topics: Humans; Multiple Myeloma; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Thalidomide
PubMed: 36394758
DOI: 10.26355/eurrev_202211_30162 -
Nutrients Jul 2023Multiple myeloma (MM) is a hematological malignancy characterized by the exponential growth of malignant plasma cells. Individuals diagnosed with MM exhibit a deficiency... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple myeloma (MM) is a hematological malignancy characterized by the exponential growth of malignant plasma cells. Individuals diagnosed with MM exhibit a deficiency in vitamin D and may suffer fatigue, a loss of muscular strength, persistent musculoskeletal aches, and pain. The objective of this systematic review and meta-analysis is to determine the prevalence of vitamin D insufficiency and deficiency in individuals diagnosed with MM.
METHODS
We searched five electronic databases using relevant keywords. The quality of the included studies was evaluated using the critical appraisal tool developed by the Joanna Briggs Institute. We employed a random-effects model and presented the findings in the form of percentages accompanied by 95% confidence intervals (CI). This protocol has been officially registered in PROSPERO under the registration number CRD42021248710.
RESULTS
The meta-analysis comprised a total of eighteen studies and found that, among patients with MM, the occurrence of serum vitamin D deficiency and insufficiency was 39.4% (95% CI: 25.8 to 52.9, n = 3746) and 34.1% (95% CI: 20.9 to 47.2, n = 3559), respectively. The findings indicate that a greater proportion of newly diagnosed patients exhibited vitamin D deficiency and insufficiency, with rates of 43.0% and 41.6%, respectively, compared to those receiving treatment (rates of 41.6% and 32.3%, respectively). The findings of the sensitivity analyses were consistent, and most of the studies (72.2%) were deemed to be of high quality. The results of Egger's test indicated the absence of publication bias.
CONCLUSIONS
Patients diagnosed with MM have been found to exhibit significantly elevated levels of both vitamin D deficiency and insufficiency. Therefore, it is recommended to consider vitamin D testing as an additional parameter in the current criteria for the clinical evaluation of MM.
Topics: Humans; Multiple Myeloma; Prevalence; Vitamin D Deficiency; Vitamin D; Vitamins; Pain
PubMed: 37513645
DOI: 10.3390/nu15143227 -
Frontiers in Oncology 2022Circulating cell-free DNA (cfDNA) detection, a non-invasive method, appears promising for genetic analyses as well as quantitative assessment of tumor burden in patients...
Circulating cell-free DNA (cfDNA) detection, a non-invasive method, appears promising for genetic analyses as well as quantitative assessment of tumor burden in patients with cancer. Although the analysis of cfDNA for clinical prognosis and monitoring disease burden in multiple myeloma (MM) has been recently studied, the results are unclear. In this meta-analysis, we explored the clinical significance of circulating cfDNA detection in patients with MM. We searched PubMed, Embase, and the Cochrane Library for eligible studies published up until July 25, 2021. Diagnostic accuracy variables were calculated and analyzed using Meta-Disc, and prognostic data were analyzed using Review Manager. Overall, seven studies comprising 235 myeloma patients met our inclusion criteria. The overall sensitivity and specificity of cfDNA to detect minimal residual disease (MRD) were 0.58 and 0.91, respectively. Moreover, higher levels of cfDNA were associated with worse progression-free survival as well as with poor overall survival. Our meta-analysis revealed that ctDNA detection has an obvious advantage in terms of MRD detection specificity, but it showed no superiority over bone marrow assessment in terms of MRD detection sensitivity, and higher levels of cfDNA were indicative of worse prognosis in patients with MM. cfDNA detection is a non-invasive method and thus shows promise as a good alternative to BM biopsies for monitoring clonal evolution and tumor burden so as to guide the treatment of patients with MM.
PubMed: 35252019
DOI: 10.3389/fonc.2022.852573 -
Medicine May 2023Pathogenesis of malignant tumors are often accompanied by aberrant expression of circular RNAs (circRNAs), indicating the potential diagnostic value of circRNAs in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pathogenesis of malignant tumors are often accompanied by aberrant expression of circular RNAs (circRNAs), indicating the potential diagnostic value of circRNAs in tumors. CircRNAs have been found to be enriched, stable and ubiquitous in serum and plasma exosomes. The study aims at evaluating the diagnostic performance of circulating (plasma and serum) exosomal circRNA in different types of cancer by synthesis of published data.
METHODS
A comprehensive literature search was conducted in PubMed, Embase, Medline and the Web of Science databases to identify potentially eligible studies published before April 2021. We conducted the meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.
RESULTS
Eleven articles comprising 21 studies were included, and a total of 1609 cases and 1498 controls were evaluated. Six types of cancer were involved in these studies, including lung cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, multiple myeloma and osteosarcoma. The pooled sensitivity and specificity were 0.72 (95% confidence interval [CI], 0.62-0.81) and 0.83 (95% CI, 0.78-0.88), respectively. Summary receiver operating characteristic curve was constructed and the pooled value of area under curve was 0.86 (95% CI, 0.83-0.89), indicating a favorable diagnostic efficacy of circulating exosomal circRNAs in malignancies.
CONCLUSIONS
In conclusion, our study evaluated the diagnostic power of circulating exosomal circRNAs in 6 types of cancer by synthesis of published data comprising 21 studies from eleven articles. The pooled analysis provided the evidence supporting circulating exosomal circRNAs as a promising noninvasive diagnostic biomarkers for malignancies.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Hepatocellular; Liver Neoplasms; RNA, Circular; Sensitivity and Specificity
PubMed: 37233410
DOI: 10.1097/MD.0000000000033872 -
Medicina (Kaunas, Lithuania) Apr 2023: Oral lichen planus (OLP) is an autoimmune, mucocutaneous, oral potentially malignant disorder (OPMD), which characteristically manifests with chronic, recalcitrant... (Review)
Review
: Oral lichen planus (OLP) is an autoimmune, mucocutaneous, oral potentially malignant disorder (OPMD), which characteristically manifests with chronic, recalcitrant lesions, with frequent flare-ups and remissions. The precise etiopathogenesis of OLP is still debatable, although it is believed to be a T-cell-mediated disorder of an unidentified antigen. Despite the availability of various treatments, no cure for OLP exists due to its recalcitrant nature and idiopathic etiology. Platelet-rich plasma (PRP) has antioxidant, anti-inflammatory, and immunomodulatory properties, in addition to its regulatory action on keratinocyte differentiation and proliferation. These salient properties substantiate the possible role of PRP in the treatment of OLP. Our systematic review focuses on assessing the therapeutic potential of PRP as a treatment modality in OLP. : We conducted a detailed literature search for studies assessing PRP as a therapeutic regimen in OLP, using the Google Scholar and PubMed/MEDLINE search engines. The search was limited to studies published from January 2000 to January 2023 and included a combination of Medical Subject Heading (MeSH) terms. ROBVIS analysis was carried out for the assessment of publication bias. Descriptive statistics were performed using Microsoft Excel. : This systematic review included five articles that met the inclusion criteria. Most of the included studies demonstrated that PRP treatment considerably ameliorated both objective and subjective symptoms in OLP subjects, with comparable efficacy to the standard corticosteroid treatment. Further, PRP therapy offers the added benefit of minimal adverse effects and recurrences. : This systematic review suggests that PRP has significant therapeutic potential for treating OLP. However, further research with larger sample sizes is imperative to corroborate these findings.
Topics: Humans; Lichen Planus, Oral; Neoplasms; Adrenal Cortex Hormones
PubMed: 37109704
DOI: 10.3390/medicina59040746 -
The Lancet. Haematology May 2023Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus... (Review)
Review
Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice.
Topics: Humans; Consensus; Nuclear Medicine; Artificial Intelligence; Hematologic Neoplasms; Molecular Imaging
PubMed: 37142345
DOI: 10.1016/S2352-3026(23)00030-3 -
Current Oncology (Toronto, Ont.) May 2022Advances in scientific understanding have led to novel therapies and improved supportive care for many patients with haematological malignancies. However, these new... (Review)
Review
UNLABELLED
Advances in scientific understanding have led to novel therapies and improved supportive care for many patients with haematological malignancies. However, these new drugs are often costly, only available at centralised health care facilities, require regular specialist reviews and lengthy treatment regimens. This leads to a significant financial burden. Understanding the impact of financial burden on haematological patients is important to appreciate the urgency of alleviating this systemic issue.
METHOD
Eligible studies were identified by systematically searching Medline, PsycINFO, CINAHL and Embase. Self-reported data reported in both quantitative and qualitative studies that described the financial burden for patients with haematological malignancies were included. Quality appraisal of the included studies was undertaken using the Joanna Briggs Institute tools. A narrative synthesis was employed. For quantitative studies, outcomes were extracted, tabulated and categorised to find similarities and differences between the studies. For qualitative studies, quotations, codes and themes were extracted and then clustered. An inductive approach derived qualitative themes.
RESULTS
Twenty studies were identified for inclusion. Of the quantitative studies most (83%) employed un-validated researcher-generated measures to assess financial burden. Between 15-59% of patients experienced a financial burden. Out-of-pocket expenditure was frequent for clinical appointments, prescription and non-prescription medication, and travel. Financial burden was associated with a worsening quality of life and living in metropolitan areas, but there was no evidence for impact on survival. Patient-centred experiences from the qualitative inquiry complemented the quantitative findings and five themes were determined: familial or household impact; reliance on others; barriers to care due to cost; and barriers to accessing financial assistance and sources of out-of-pocket expenses.
CONCLUSION
The impacts of financial burden are yet to be fully appreciated in haematological malignancies, exacerbated by the heterogeneous methods employed by researchers. Future work should focus on identifying the long-term ramifications of financial burden for patients and should trial interventions to reduce its prevalence and patient impacts.
Topics: Financial Stress; Hematologic Neoplasms; Humans; Qualitative Research; Quality of Life
PubMed: 35735414
DOI: 10.3390/curroncol29060305