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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 -
Cancer Cell International Sep 2023In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the... (Review)
Review
BACKGROUND
In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients.
METHODS
PubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR).
RESULTS
Eleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively.
CONCLUSIONS
In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms.
PubMed: 37670301
DOI: 10.1186/s12935-023-03045-y -
Therapeutic Advances in Vaccines and... 2023Patients with plasma cell dyscrasia are at a higher risk of developing a severe Coronavirus-2019 (COVID-19) infection. Here we present a systematic review of clinical... (Review)
Review
BACKGROUND
Patients with plasma cell dyscrasia are at a higher risk of developing a severe Coronavirus-2019 (COVID-19) infection. Here we present a systematic review of clinical studies focusing on the immune response to the COVID-19 vaccination in patients with plasma cell dyscrasia.
OBJECTIVES
This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to utilize the results to improve day-to-day practice.
DESIGN
Systematic Review.
METHODS
Online databases (PubMed, CINAHL, Ovid, and Cochrane) were searched following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Only articles published in the English language were included. Out of 59 studies, nine articles (seven prospective and two retrospective studies) were included in this systematic review. Abstracts, case reports, and case series were excluded.
RESULTS
In all nine studies ( = 1429), seroconversion post-vaccination was the primary endpoint. Patients with plasma cell disorders had a lower seroconversion rate compared to healthy vaccinated individuals and the overall percentage of seroconversion ranged between 23% and 95.5%. Among patients on active therapy, lower seroconversion rates were seen on an anti-CD38 agent, ranging from 6.5 up to 100%. In addition, a significantly lower percentage was recorded in older patients, especially in those aged equal to or greater than 65 years and those who have been treated with multiple therapies previously. Only one study reported a statistically significant better humoral response rate with the mRNA vaccine compared to ADZ1222/Ad26.Cov.S.
CONCLUSION
Variable seropositive rates are seen in patients with plasma cell dyscrasia. Lower rates are reported in patients on active therapy, anti-CD38 therapy, and elderly patients. Hence, we propose patients with plasma cell dyscrasias should receive periodic boosters to maintain clinically significant levels of antibodies against COVID-19.
REGISTRATION
PROSPERO ID: CRD42023404989.
PubMed: 37645011
DOI: 10.1177/25151355231190497 -
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 -
Cancer Cell International Aug 2023Unlike improved treatment response in multiple myeloma (MM), the mortality rate in MM is still high. The study's aim is to investigate the potential role of circRNAs as... (Review)
Review
Unlike improved treatment response in multiple myeloma (MM), the mortality rate in MM is still high. The study's aim is to investigate the potential role of circRNAs as a new biomarker for diagnosis, prognosis, and clinicopathological features of MM. We identified studies through Web of Science, Scopus, PubMed and ProQuest databases, and Google Scholar to August 2022. The SEN, SPE, PLR, NLR, DOR, and AUC were combined to investigate the diagnostic performance of circRNAs in MM. Also, HR and RR were used for prognostic and clinicopathological indicators, respectively. 12 studies for prognosis, 9 studies about diagnosis, and 13 studies regarding clinicopathological features. The pooled SEN, SPE, DOR, and AUC were 0.82, 0.76, 14.70, and 0.86, respectively for the diagnostic performance of circRNAs. For the prognostic performance, oncogene circRNAs showed a poor prognosis for the patients (HR = 3.71) and tumor suppressor circRNAs indicated a good prognosis (HR = 0.31). Finally, we discovered that dysregulation of circRNAs is associated with poor clinical outcomes in beta-2-microglobulin (RR = 1.56), Durie-Salmon stage (RR = 1.36), and ISS stage (RR = 1.79). Furthermore, the presence of del(17p) and t(4;14) is associated with circRNA dysregulation (RR = 1.44 and 1.44, respectively). Our meta-analysis demonstrates that the expression analysis of circRNAs is valuable for MM's diagnosis and prognosis determination. Also, dysregulation of circRNAs is associated with poor clinicopathological features and can be used as the applicable biomarkers for evaluating treatment effectiveness.
PubMed: 37633891
DOI: 10.1186/s12935-023-03028-z -
EJHaem Aug 2023Long-term follow-up of multiple myeloma (MM) clinical trials are needed to assess long-term outcomes. We aimed to investigate the length of follow-up of all phase III MM...
Long-term follow-up of multiple myeloma (MM) clinical trials are needed to assess long-term outcomes. We aimed to investigate the length of follow-up of all phase III MM clinical trials. Median follow-up duration of clinical trials of newly diagnosed MM was longer when compared to relapsed/refractory MM clinical trials (42.7 vs. 20.5 months, respectively). The follow-up duration of phase III clinical trials in MM is relatively short when compared to the improved outcomes in the current era. Efforts should be made to facilitate long-term clinical trials follow-up and/or publication of results of updated results.
PubMed: 37601879
DOI: 10.1002/jha2.680 -
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 -
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 -
Cancer Medicine Sep 2023HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using HPV circulating tumor DNA (HPV ctDNA) can be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using HPV circulating tumor DNA (HPV ctDNA) can be used as a promising marker for predicting recurrence in HPV-related cancers remains to be validated. Here we conducted a systematic review and meta-analysis to assess its effectiveness in predicting treatment response.
METHODS
We conducted a systematic literature search of online databases, including PubMed, Embase, Scopus, and the Cochrane Library, up to December 2022. The goal was to identify survival studies that evaluated the potential of plasma HPV ctDNA at baseline and end-of-treatment (EoT) in predicting recurrence of related cancers. Hazard ratios were estimated directly from models or extracted from Kaplan-Meier plots.
RESULTS
The pooled effect of HPV ctDNA presence on disease recurrence was estimated to be HR = 7.97 (95% CI: [3.74, 17.01]). Subgroup analysis showed that the risk of recurrence was HR = 2.17 (95% CI: [1.07, 4.41]) for baseline-positive cases and HR = 13.21 (95% CI: [6.62, 26.36]) for EoT-positive cases. Significant associations were also observed between recurrence of oropharyngeal squamous cell carcinoma (HR = 12.25 (95% CI: [2.62, 57.36])) and cervical cancer (HR = 4.60 (95% CI: [2.08, 10.17])) in plasma HPV ctDNA-positive patients.
CONCLUSIONS
The study found that HPV ctDNA detection can predict the rate of relapse or recurrence after treatment, with post-treatment measurement being more effective than baseline assessment. HPV ctDNA could be used as a surrogate or incorporated with other methods for detecting residual disease.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Circulating Tumor DNA; Neoplasm Recurrence, Local; Head and Neck Neoplasms
PubMed: 37492996
DOI: 10.1002/cam4.6377 -
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