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Clinical Lymphoma, Myeloma & Leukemia Feb 2024Multiple myeloma (MM) accounts for 10% of hematologic cancers in the U.S.; however, incidence and mortality occur disproportionately between racial groups in real-world...
Multiple myeloma (MM) accounts for 10% of hematologic cancers in the U.S.; however, incidence and mortality occur disproportionately between racial groups in real-world settings. Our study's objective was to systematically characterize the disparities in overall survival (OS) among Black and White patients with MM in the US using real-world evidence studies. A systematic literature review was undertaken by searching Embase and MEDLINE for observational studies conducted in the US, published between January 1, 2015 and October 25, 2021, and reporting OS for Black and White patients with MM. Records were reviewed by 2 independent researchers. OS data were extracted as hazard ratios (HR), median survival, or %, with methods of adjustment, as reported. Evidence quality was assessed by data source, population, and variables for which HRs for risk of death were adjusted. We included 33 US studies comprising 410,086 patients (21.5% Black; 78.5% White) with MM. Receipt of treatment varied; however, most studies reported that patients either underwent stem cell transplant and/or received systemic therapy. HRs from 9 studies were considered "high quality" by comparing nationally representative, generalizable cohorts and adjusting for key prognostic, treatment, and/or socioeconomic factors. After adjustment, these data suggested that Black patients exhibit similar or superior survival outcomes compared with their White counterparts. When data are adjusted for important confounders, Black patients exhibit better or equal survival to White patients, indicating that similarities in patient populations and equal access to treatment can bridge the disparity in patient outcomes between races.
Topics: Humans; Healthcare Disparities; Multiple Myeloma; Proportional Hazards Models; Racial Groups; Black or African American; White; Survival Rate
PubMed: 37923653
DOI: 10.1016/j.clml.2023.09.009 -
Cancers Sep 2023The presence of a serum paraprotein (PP) is usually associated with plasma-cell dyscrasias, Waldenstrom Macroglobulinemia/lymphoplasmacytic lymphoma, and... (Review)
Review
The presence of a serum paraprotein (PP) is usually associated with plasma-cell dyscrasias, Waldenstrom Macroglobulinemia/lymphoplasmacytic lymphoma, and cryoglobulinemia. However, PP is also often reported in other high- and low-grade B-cell malignancies. As these reports are sparse and heterogeneous, an overall view on this topic is lacking, Therefore, we carried out a complete literature review to detail the characteristics, and highlight differences and similarities among lymphoma entities associated with PP. In these settings, IgM and IgG are the prevalent PP subtypes, and their serum concentration is often low or even undetectable without immunofixation. The relevance of paraproteinemia and its prevalence, as well as the impact of IgG vs. IgM PP, seems to differ within B-NHL subtypes and CLL. Nonetheless, paraproteinemia is almost always associated with advanced disease, as well as with immunophenotypic, genetic, and clinical features, impacting prognosis. In fact, PP is reported as an independent prognostic marker of poor outcome. All the above call for implementing clinical practice, with the assessment of paraproteinemia, in patients' work-up. Indeed, more studies are needed to shed light on the biological mechanism causing more aggressive disease. Furthermore, the significance of paraproteinemia, in the era of targeted therapies, should be assessed in prospective trials.
PubMed: 37760410
DOI: 10.3390/cancers15184440 -
Critical Reviews in Oncology/hematology Dec 2023A registered (PROSPERO - CRD42022346462) systematic review and meta-analysis was conducted of all-grade infections amongst adult patients receiving CAR-T therapy for... (Meta-Analysis)
Meta-Analysis Review
A registered (PROSPERO - CRD42022346462) systematic review and meta-analysis was conducted of all-grade infections amongst adult patients receiving CAR-T therapy for haematological malignancy. Meta-analysis of pooled incidence, using random effects model, was conducted. Cochran's Q test examined heterogeneity. 2678 patients across 33 studies were included in the primary outcome. Forty-percent of patients (95% CI: 0.33 - 0.48) experienced an infection of any grade. Twenty-five percent of infection events (95% CI: 0.16 - 0.34) were severe. Late infections were as common as early infections (IRR = 0.86, 95% CI: 0.38 - 1.98). All-grade infections, bacterial and viral infections were highest in myeloma patients at 57%, 37% and 28% respectively. Patients with NHL more commonly experienced late infections. Pooled rate of invasive candidiasis/yeast infections was 2% in studies utilizing anti-yeast prophylaxis. This review identified a high rate of all-grade infections, moderate rate of severe infections, and myeloma as a high-risk haematological group.
Topics: Adult; Humans; Multiple Myeloma; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Hematologic Neoplasms; Hematology
PubMed: 37739146
DOI: 10.1016/j.critrevonc.2023.104134 -
JPMA. the Journal of the Pakistan... Aug 2023To review biochemical parameters, clinical characteristics, demographics, radiological and histopathological findings, treatment modalities and outcomes used to examine...
OBJECTIVE
To review biochemical parameters, clinical characteristics, demographics, radiological and histopathological findings, treatment modalities and outcomes used to examine patients with coexisting multiple myeloma and prostate adencocarcinoma.
METHODS
The systematic review comprised search on PubMed, Google Scholar, Science Direct and the Directory of Open Access Journal databases for case reports published till June 1, 2022. The search was done in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using appropriate key words. Case reports included were those dealing exclusively with human subjects, were published in the English language and had free, full-text, public access. Quality assessment was done using Joanna Briggs Institute's Critical Appraisal Checklist for Case Reports. Data was extracted and the case reports were evaluated for demographic, diagnostic and treatment parameters.
RESULTS
Of the 515 studies initially identified, 5(0.97%) were analysed; all males with mean age 68.6±10.78 years. The most common symptom reported at presentation was low back pain 3(60%), Osteolytic lesions were seen in 4(80%) patients on imaging with elevated prostate surface antigen levels. Anaemia was found in 3(60%) patients and 2(40%) had thrombocytopenia.
CONCLUSION
Multiple myeloma and prostate adenocarcinoma can coexist although it is rare. Awareness regarding the possible coexistence of the two prominent cancer types may further help clinicians during their practice in considering multiple myeloma as a differential diagnosis when encountered with patients having osteolytic bony lesions along with elevated levels of prostate-specific antigen.
PROSPERO REGISTRATION NUMBER
CRD42022334906.
Topics: Male; Humans; Middle Aged; Aged; Multiple Myeloma; Prostate; Prostatic Neoplasms; Prostate-Specific Antigen; Adenocarcinoma
PubMed: 37697762
DOI: 10.47391/JPMA.8068 -
Blood Cancer Journal Sep 2023Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an... (Meta-Analysis)
Meta-Analysis
Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.
Topics: Humans; Waldenstrom Macroglobulinemia; Rituximab; Bortezomib; Clinical Protocols; Cyclophosphamide
PubMed: 37679351
DOI: 10.1038/s41408-023-00916-5 -
BMJ Open Aug 2023To systematically review and meta-analyse the evidence for effect modification by refractory status and number of treatment lines in relapsed/refractory multiple myeloma... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically review and meta-analyse the evidence for effect modification by refractory status and number of treatment lines in relapsed/refractory multiple myeloma (RRMM); and to assess whether effect modification is likely to invalidate network meta-analyses (NMA) that assume negligible modification.
DESIGN
Systematic review, meta-analysis and simulation.
DATA SOURCES
We systematically searched the literature (e.g., OVID Medline) to identify eligible publications in February 2020 and regularly updated the search until January 2022. We also contacted project stakeholders (including industry) ELIGIBILITY CRITERIA: Phase 2 and 3 randomised controlled trials reporting stratified estimates for comparisons with at least one of a prespecified set of treatments relevant for use in Norwegian RRMM patients.
OUTCOMES
We used meta-analysis to estimate relative HRs (RHRs) for overall survival (OS) and progression-free survival (PFS) with respect to refractory status and number of treatment lines. We used the estimated RHRs in simulations to estimate the percentage of NMA results expected to differ significantly in the presence versus absence of effect modification.
RESULTS
Among the 42 included publications, stratified estimates were published by and extracted from up to 18 (43%) publications and on as many as 8364 patients. Within-study evidence for effect modification is very weak (p>0.05 for 47 of 49 sets of stratified estimates). The largest RHR estimated was 1.32 (95% CI 1.18 to 1.49) for the modifying effect of refractory status on HR for PFS. Simulations suggest that, in the worst case, this would result in only 4.48% (95% CI 4.42% to 4.54%) of NMA estimates differing statistically significantly in the presence versus absence of effect modification.
CONCLUSIONS
Based on the available evidence, effect modification appears to be sufficiently small that it can be neglected in adequately performed NMAs. NMAs can probably be relied on to provide estimates of HRs for OS and PFS in RRMM, subject to caveats discussed herein.
Topics: Humans; Multiple Myeloma; Network Meta-Analysis; Computer Simulation; Industry; MEDLINE
PubMed: 37643851
DOI: 10.1136/bmjopen-2022-067966 -
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 Immunology 2023Data on non-infectious cryoglobulinemic vasculitis (NICV) is scarce, especially concerning the management of relapses, which are troublesome. We aimed to investigate...
BACKGROUND
Data on non-infectious cryoglobulinemic vasculitis (NICV) is scarce, especially concerning the management of relapses, which are troublesome. We aimed to investigate risk factors for relapse in NICV.
METHODS
A systematic literature search of CINAHL, Embase, MEDLINE, Scopus, and the Web of Science databases was implemented until April 2023. Eligible studies included randomized control trials, observational studies, and case series with ≥4 patients. Two reviewers independently extracted data and assessed the quality of the eligible studies.
RESULTS
A total of 3,724 articles were retrieved from a database search, with 27 studies meeting the inclusion criteria for review. Most studies (n = 23) detailed relapses, with the time to relapse varying between 1 and 80 months. The relapse rate was reported at 28% in Type I NICV and ranged from 22% to 60% in mixed NICV. Risk factors for relapse in NICV were identified based on the cryoglobulin subtype and correlated with clinical and immunological responses to varying treatment regimens. Type I NICV with an associated lymphoproliferative disorder exhibited a response-relapse pattern. Cutaneous and articular involvement and incomplete clinical and immunological responses to treatment, particularly corticosteroid monotherapy and occasionally rituximab, influence the risk of relapse in Type II and Type III NICV.
CONCLUSION
Our findings underscore the significance of attaining both clinical and immunological responses and identifying risk factors for relapse in NICV. Appropriate risk stratification for NICV patients is essential for the successful implementation of effective treatment strategies.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023408140.
Topics: Humans; Cryoglobulinemia; Vasculitis; Rituximab; Treatment Outcome; Recurrence
PubMed: 37483620
DOI: 10.3389/fimmu.2023.1215345 -
Blood Advances Oct 2023Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell... (Meta-Analysis)
Meta-Analysis
Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein-coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks. A literature search used MEDLINE, EMBASE, and Cochrane to identify relevant studies between inception and February 10, 2023, including major conference presentations. Phase 1b-3 clinical trials and observational studies were included. Sixteen clinical trials comprising 1666 patients were included. Median follow-up was 7.6 months and 38% of the cohort had penta-drug refractory disease. Pooled prevalence of all-grade infections was 56%, whereas the prevalence of grade ≥3 infections was 24%. Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs 20%). Similarly, patients treated with bispecifics in combination with other agents had significantly higher rate of all-grade infection than those receiving monotherapy (71% vs 52%). In observational studies (n = 293), excluded from the primary analysis to ensure no overlap with patients in clinical trials, several infections classically associated with T-cell depletion were identified. This systematic review identifies BCMA-targeted bispecifics and bispecific combination therapy as having higher infection risk, requiring vigilant infection screening and prophylaxis strategies.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; B-Cell Maturation Antigen; Immunotherapy; T-Lymphocytes; CD3 Complex
PubMed: 37467036
DOI: 10.1182/bloodadvances.2023010539 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2023Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common...
BACKGROUND
Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common affected site, usually causing macroglossia. Biopsy is essential for the diagnosis and the occurrence of its systemic form is mandatory to be investigated. This systematic review evaluated the existing information in the literature on Amyloidosis in the oral cavity to allow a more comprehensive and updated analysis of its clinicopathological characteristics, as well as to explore the main forms of treatment and prognostic factors.
MATERIAL AND METHODS
Electronic searches were undertaken in five databases supplemented by manual scrutiny.
RESULTS
A total of 111 studies were included with 158 individuals.
CONCLUSIONS
The disease had a higher prevalence in women, the tongue was the most affected site, as well as the systemic form of the disease. The worst prognosis was for cases of systemic amyloidosis associated with multiple myeloma.
Topics: Humans; Female; Amyloidosis; Macroglossia; Multiple Myeloma; Tongue Diseases; Tongue
PubMed: 37330968
DOI: 10.4317/medoral.25761