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Annals of Medicine Dec 2023Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard therapies.
OBJECTIVE
This study aimed to assess the efficacy and safety of VEN-based treatments in RR MM patients.
MATERIALS AND METHODS
Comprehensive studies were searched in PubMed, Embase, Web of Science and Cochrane library. Efficacy was assessed by overall response rate (ORR), strict complete response rate (sCR), complete response rate (CR), very good partial response rate (VGPR) and partial response rate (PR).
RESULTS
Seven studies containing 482 subjests were included. The pooled ORR, ≥ CR (sCR + CR), VGPR and PR were 68% (51%-85%), 24% (13%-35%), 25% (17%-34%) and 17% (11%-24%) respectively. Multi-drug treatments were superior to VEN ± dexamethasone (Dex) treatments in ORR (82% vs 42%, = .003) and ≥ CR (36% vs 7%, < 0.00001). Subgroup analysis indicated patients achieve higher ORR who harboring t(11;14) translocation or containing high BCL-2 expression.
CONCLUSIONS
VEN-containing regimens could be suggested as effective and safe treatments to RR MM patients with t(11;14) or high BCL-2 levels.
Topics: Humans; Multiple Myeloma; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 36911885
DOI: 10.1080/07853890.2023.2186480 -
Journal of Medical Internet Research Aug 2023The internet is a primary source of health information for patients, supplementing physician care. Google Trends (GT), a popular tool, allows the exploration of public... (Review)
Review
BACKGROUND
The internet is a primary source of health information for patients, supplementing physician care. Google Trends (GT), a popular tool, allows the exploration of public interest in health-related phenomena. Despite the growing volume of GT studies, none have focused explicitly on oncology, creating a need for a systematic review to bridge this gap.
OBJECTIVE
We aimed to systematically characterize studies related to oncology using GT to describe its utilities and biases.
METHODS
We included all studies that used GT to analyze Google searches related to malignancies. We excluded studies written in languages other than English. The search was performed using the PubMed engine on August 1, 2022. We used the following search input: "Google trends" AND ("oncology" OR "cancer" or "malignancy" OR "tumor" OR "lymphoma" OR "multiple myeloma" OR "leukemia"). We analyzed sources of bias that included using search terms instead of topics, lack of confrontation of GT statistics with real-world data, and absence of sensitivity analysis. We performed descriptive statistics.
RESULTS
A total of 85 articles were included. The first study using GT for oncology research was published in 2013, and since then, the number of publications has increased annually. The studies were categorized as follows: 22% (19/85) were related to prophylaxis, 20% (17/85) pertained to awareness events, 11% (9/85) were celebrity-related, 13% (11/85) were related to COVID-19, and 47% (40/85) fell into other categories. The most frequently analyzed cancers were breast (n=28), prostate (n=26), lung (n=18), and colorectal cancers (n=18). We discovered that of the 85 studies, 17 (20%) acknowledged using GT topics instead of search terms, 79 (93%) disclosed all search input details necessary for replicating their results, and 34 (40%) compared GT statistics with real-world data. The most prevalent methods for analyzing the GT data were correlation analysis (55/85, 65%) and peak analysis (43/85, 51%). The authors of only 11% (9/85) of the studies performed a sensitivity analysis.
CONCLUSIONS
The number of studies related to oncology using GT data has increased annually. The studies included in this systematic review demonstrate a variety of concerning topics, search strategies, and statistical methodologies. The most frequently analyzed cancers were breast, prostate, lung, colorectal, skin, and cervical cancers, potentially reflecting their prevalence in the population or public interest. Although most researchers provided reproducible search inputs, only one-fifth used GT topics instead of search terms, and many studies lacked a sensitivity analysis. Scientists using GT for medical research should ensure the quality of studies by providing a transparent search strategy to reproduce results, preferring to use topics over search terms, and performing robust statistical calculations coupled with sensitivity analysis.
Topics: Female; Humans; Male; Bias; Biomedical Research; COVID-19; Internet; Search Engine; Neoplasms
PubMed: 37540544
DOI: 10.2196/47582 -
Cureus Sep 2021Multiple myeloma (MM) is an indolent B-cell malignancy, where treatment is aimed at preventing organ dysfunction from light chain accumulation (slowing disease... (Review)
Review
Multiple myeloma (MM) is an indolent B-cell malignancy, where treatment is aimed at preventing organ dysfunction from light chain accumulation (slowing disease progression) and inducing remission. Allogeneic stem cell transplant (allo-SCT), through graft versus myeloma (GVM) effects, has the potential to induce remission to a potentially curative-like state. In this systematic review, we aimed to understand this relationship to the risks and severity of disease in categorized patients and gain an updated comprehension of the future of allo-SCT in MM treatment. We conducted this review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched the PubMed database to obtain the specified literature with both the use of keywords and Medical Subject Headings (MeSH). A total of 16 relevant articles were included for discussion after the quality appraisal was completed, as appropriate, by either the Cochrane tool or Newcastle-Ottawa checklist. Our review concludes that while allo-SCT may benefit high-risk patients, successful procedures may incorporate a tandem autologous hematopoietic stem cell transplant approach in combination with novel pharmacologic contributions for which there is an observed synergy in the modulation of the immunologic microenvironment. Furthermore, tailored patient selection by evaluating pre-transplant factors including high-risk cytogenetics, age, and pre-salvage International Staging System (ISS) can predict post-transplantation success including non-relapse mortality. Successive research should continue to revise and update treatment options as the evolving therapeutic drug regimens may change over the course of indolent disease.
PubMed: 34725596
DOI: 10.7759/cureus.18334 -
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 -
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 -
BMC Endocrine Disorders Jan 2022Adipocytes and their products, adipocytokines, play important roles in the generation and development of multiple myeloma (MM). Studies have demonstrated some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adipocytes and their products, adipocytokines, play important roles in the generation and development of multiple myeloma (MM). Studies have demonstrated some adipocytokines to be associated with MM, although those results are controversial. Therefore, we conducted a meta-analysis to verify the association of adipocytokines with MM.
METHODS
We performed a systematic retrieval of literature published prior to 26 October 2021. Standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated to evaluate pooled effects. Subgroup analysis and meta-regression analysis were conducted to detect sources of heterogeneity. Sensitivity analysis was performed to evaluate the stability of the study. Publication bias was assessed by funnel plots and Egger's linear regression test.
RESULTS
Ten eligible studies with 1269 MM patients and 2158 controls were included. The pooled analyses indicated that circulating leptin levels of MM patients were significantly higher than control levels (SMD= 0.87, 95%CI: 0.33 to 1.41), while the circulating adiponectin levels in MM patients were significantly lower than controls with a pooled SMD of -0.49 (95%CI: -0.78 to -0.20). The difference of circulating resistin levels were not significant between MM patients and controls (SMD= -0.08, 95%CI: -0.55 to 0.39). Subgroup analysis and meta-regression analysis found that sample size, age, and sex were possible sources of heterogeneity. Sensitivity analysis demonstrated our pooled results to be stable.
CONCLUSION
Decreased circulating adiponectin and increased leptin levels were associated with the occurrence and development of MM. Adiponectin and leptin may be potential biomarkers and therapeutic targets for MM.
Topics: Adipokines; Biomarkers, Tumor; Case-Control Studies; Humans; Multiple Myeloma
PubMed: 35073877
DOI: 10.1186/s12902-022-00939-2 -
Medicine Nov 2016Renal insufficiency is a common and severe complication of patients with multiple myeloma. The aim of this study was to evaluate bortezomib-based treatment for multiple... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Renal insufficiency is a common and severe complication of patients with multiple myeloma. The aim of this study was to evaluate bortezomib-based treatment for multiple myeloma patients with renal insufficiency.
METHODS
The Cochrane Library, Embase, PubMed, ISI, China National Knowledge Infrastructure, Chinese Biomedical Literature Service System, Chongqing VIP Database, and Wan Fang Data were systematically searched to identify observational studies from January 1, 2001, to December 31, 2015. Myeloma response rate and renal remission rate were pooled by using risk ratio and 95% confidence interval (CI). The Cochran Q and I statistics were used to assess heterogeneity. Sensitivity analysis was performed to test the feasibility of pooled results. Publication bias was conducted when included studies were ≥9. Furthermore, grades of evidence were performed to evaluate study quality.
RESULTS
Eleven retrospective cohort studies were included in the final analysis. The number of available studies and risk ratios (95% CI) were, respectively, 10 and 1.48 (95% CI: 1.28-1.71) for myeloma overall response, 6 and 3.69 (95% CI: 2.22-6.13) for myeloma complete response, 9 and 1.47 (95% CI: 1.28-1.69) for renal overall remission, and 8 and 1.49 (95% CI: 1.26-1.75) for renal complete remission. No significant publication bias was observed and sensitivity analysis confirmed the stability of results. The overall qualities of evidence were high for myeloma complete response and medium for the other 3 outcomes based on the Grading of Recommendations, Assessment, Development and Evaluation system.
CONCLUSION
Current evidence indicated that bortezomib-based treatment could improve myeloma overall response (especially myeloma complete response) and renal overall remission (including renal complete remission).
Topics: Antineoplastic Agents; Bortezomib; Humans; Multiple Myeloma; Observational Studies as Topic; Remission Induction; Renal Insufficiency
PubMed: 27861343
DOI: 10.1097/MD.0000000000005202 -
Future Oncology (London, England) 2015Novel drugs such as immunomodulators and proteasome inhibitors have improved the survival of patients with multiple myeloma. Like all therapeutic agents, appropriate... (Review)
Review
Novel drugs such as immunomodulators and proteasome inhibitors have improved the survival of patients with multiple myeloma. Like all therapeutic agents, appropriate dosing based on metabolism and clearance is important to maintain efficacy while avoiding toxicity. Hepatic impairment (HI) in multiple myeloma patients is rare but well described either due to disease or therapy-related factors. However, limited data are available on the appropriate use and dosing of the novel agent therapeutics in myeloma patients with HI. Furthermore, data on HI secondary to the novel agent toxicity are also sparse. This systematic review highlights the evidence on the use of novel agents like thalidomide, lenalidomide, pomalidomide, bortezomib and carfilzomib in patients with HI as well as their associated hepatic toxicities.
Topics: Antineoplastic Agents; Humans; Immunologic Factors; Liver Diseases; Multiple Myeloma; Proteasome Inhibitors; Treatment Outcome
PubMed: 25675129
DOI: 10.2217/fon.14.270 -
Cancers Dec 2022Patient-reported outcomes (PROs) are becoming increasingly important in supporting clinical outcomes in clinical trials. In multiple myeloma (MM), PRO measurement is... (Review)
Review
BACKGROUND
Patient-reported outcomes (PROs) are becoming increasingly important in supporting clinical outcomes in clinical trials. In multiple myeloma (MM), PRO measurement is useful to reveal how treatment affects physical, psychosocial, and functional behaviour as well as symptoms and treatment-related adverse events to evaluate the benefit-risk ratio of a particular drug or drug combination. We report the types of PRO instruments used in MM, the frequency in which they are utilised in randomised controlled trials (RCTs), and the consistency of their reporting.
METHODS
The European Hematology Association (EHA) supports the development of guidelines for the use of PROs in adult patients with haematological malignancies. The first step is the present systematic review of the literature. MEDLINE and CENTRAL were searched for RCTs in MM between 2015 and 2020. Study design, characteristics of MM and its treatment, the primary outcomes, and the types of PRO instrument(s) were extracted using a predefined template. Additionally, in a stepwise approach, it was assessed whether the identified instruments had been validated for multiple myeloma patients, patients with haematological malignancies, or cancer patients.
RESULTS
Following screening for RCTs, 283 studies were included for review from 10,707 records retrieved, and 118 of these planned the use of PRO measures. Thirty-eight PRO instruments were reported. The most frequently used instrument (92 studies) was the EORTC QLQ-30. The EORTC-MY20 MM-specific questionnaire was the second most frequently used (50 studies), together with the EQ-5D (50 studies). Only 19 PRO instruments reported were consistent with the trial registry. Furthermore, in 58 publications, the information on PRO instruments differed between the publication and the trial registry. Further, information on PRO in HTA reports was available for 26 studies, of which 18 reports were consistent with the trial registries. Out of the 38 instruments used, six had been validated for patients with multiple myeloma (the most frequently used), six for patients with haematological malignancies, and 10 for cancer patients in general.
CONCLUSIONS
The findings indicate that the measurement of PROs in RCTs for MM is underutilised, underreported, and often inconsistent. Guidelines for the appropriate use of PROs in MM are needed to ensure standardisation in selection and reporting. Furthermore, not all PRO instruments identified have been validated for myeloma patients or patients with haematological malignancies. Thus, guidelines for the appropriate use and reporting of PROs are needed in MM to ensure standardisation in the selection and reporting of PROs.
PubMed: 36497488
DOI: 10.3390/cancers14236007 -
Journal of Craniovertebral Junction &... 2023Multiple Myeloma is a B-cell malignancy which can cause variety of lesions of the spine and spinal cord. The management of patients with spinal cord compression (SCC),... (Review)
Review
BACKGROUND
Multiple Myeloma is a B-cell malignancy which can cause variety of lesions of the spine and spinal cord. The management of patients with spinal cord compression (SCC), and the efficacy and security of minimally invasive therapeutic approaches, are the main topics of discussion.
METHODS
To systematically review the scientific literature on neurosurgical aspects of MM spinal cord lesion management, a search was conducted among scientific papers in the databases ScienceDirect, Cochrane Library, and PubMed using keywords and Boolean operators. These comprise MM and lesions of the spine and spinal cord. Each database was searched from the earliest available article to January 2017.
RESULTS
According to the literature, low-dose radiotherapy, antimyeloma medications, and bisphosphonates comprise the mainstay management for symptomatic spinal lesions. The decision to operation is based on presence of myelopathy and degree of spinal cord compression.
CONCLUSIONS
As a result of the analysis, the following conclusions may be drawn: (1) surgery is a valuable option for MM patients with symptomatic spinal involvement who experience rapid neurological deterioration with SCC and/or mechanical instability and (2) it is important to ensure that the benefits of surgical treatment outweigh the risks, as patients with MM are susceptible to infections.
PubMed: 38268680
DOI: 10.4103/jcvjs.jcvjs_111_23