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Efficacy and safety of canakinumab treatment in schnitzler syndrome: A systematic literature review.Seminars in Arthritis and Rheumatism Aug 2020Schnitzler syndrome is a rare autoinflammatory disorder characterized by chronic urticarial rash and a monoclonal gammopathy, accompanied by intermittent fever, bone... (Review)
Review
BACKGROUND
Schnitzler syndrome is a rare autoinflammatory disorder characterized by chronic urticarial rash and a monoclonal gammopathy, accompanied by intermittent fever, bone pain, and arthralgia or arthritis. Canakinumab is a fully human monoclonal anti-interleukin-1β (IL-1β) antibody proven to be effective in IL-1 driven autoinflammatory disorders.
METHODS
We systematically searched PubMed and Embase to include all types of studies on canakinumab treatment in Schnitzler syndrome published until March 16, 2020.
RESULTS
Since 2011, 7 publications have been reported on canakinumab treatment in 34 patients with Schnitzler syndrome. The cumulative follow-up was 253 months, and 5 studies had a follow-up duration of 12 months or more. A complete response during treatment was reported in 58.6% of patients; all other patients had a partial response. Two hundred and seven adverse events were reported in 23 patients. Infection (n = 79) was the most common adverse event. One patient died from sepsis due to atypical mycobacterial infection.
CONCLUSION
Based on the results of the current systematic review, canakinumab is an effective long-term treatment with a favorable safety profile in patients with Schnitzler syndrome.
Topics: Antibodies, Monoclonal, Humanized; Female; Humans; Male; Schnitzler Syndrome; Treatment Outcome
PubMed: 32502728
DOI: 10.1016/j.semarthrit.2020.05.002 -
Journal of Bone and Mineral Metabolism Jan 2018Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in the elderly. A number of studies have investigated the relationship between MGUS and... (Meta-Analysis)
Meta-Analysis Review
Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in the elderly. A number of studies have investigated the relationship between MGUS and bone health outcomes including bone mineral density (BMD), osteoporosis and fractures, but no meta-analysis exists. We conducted a systematic review and exploratory meta-analysis comparing bone health outcomes in patients with MGUS. Two independent authors searched PubMed and Scopus from inception until 19 October 2016. A meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD was conducted. Standardised mean differences (SMD) ± 95% confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures. Of 174 initial hits, 10 studies of moderate methodological quality were eligible, including 8711 individuals with MGUS vs. 52,865 controls. Compared to controls, subjects with MGUS showed significantly lower values for radial cortical volumetric BMD (1 study; SMD = -5.45, 95% CI: -7.24 to -3.66), but not at the lumbar spine, femoral neck or hip. The incidence of fractures was higher in people with MGUS (n = 7466) vs. controls (n = 52,304) (RR = 1.36, 95% CI 1.28-1.44, I = 0%) over a median of 12.5-year follow-up. The incidence of vertebral fractures was particularly elevated (RR = 2.50, 95% CI 1.53-4.06) although limited to two studies. In conclusion, although with limitations, our preliminary meta-analysis suggests that patients with MGUS are at higher risk of fractures despite evidence for differences in BMD being equivocal. Future longitudinal research is required to confirm our findings and determine if fracture prevention interventions are warranted in people with MGUS.
Topics: Aged; Bone Density; Bone and Bones; Case-Control Studies; Cross-Sectional Studies; Female; Fractures, Bone; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Monoclonal Gammopathy of Undetermined Significance; Odds Ratio; Prevalence
PubMed: 28243796
DOI: 10.1007/s00774-017-0817-8 -
Hematology (Amsterdam, Netherlands) Dec 2022Despite conspicuous advances in innovating novel drugs and combination regimens in multiple myeloma (MM) in recent decades, the most appropriate maintenance regimens... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite conspicuous advances in innovating novel drugs and combination regimens in multiple myeloma (MM) in recent decades, the most appropriate maintenance regimens after inductive therapy are still controversial and opaque.
OBJECTIVE
We aimed to identify the most effective maintenance treatment for newly diagnosed multiple myeloma (NDMM) patients via network meta-analysis.
METHOD
We searched PubMed, Embase, Cochrane Library, Scopus, and Google Scholars from inception to April, 2022. Odds ratios (ORs) were generated for dichotomous variants. The primary endpoint was overall survival (OS).
RESULTS
Eventually a total of 19 trials, including 11 treatments and 8337 patients, were included in this analysis. For OS, lenalidomide (OR ranged from 1.61 to 1.99) and daratumumab (OR ranged from 1.83 to 2.41) showed significant efficacy over placebo. Maintenance therapy comprising lenalidomide-carfilzomib (OR ranged from 3.19 to 6.95), lenalidomide-prednisone (OR ranged from 2.62 to 4.44), bortezomib-thalidomide (OR ranged from 2.48 to 3.64), daratumumab (OR ranged from 2.0 to 2.98), lenalidomide (OR ranged from 1.4 to 3.19), ixazomib (OR ranged from 1.36 to 2.05), thalidomide (OR ranged from 1.5 to 1.86) demonstrated significant effects in prolongin PFS compared with placebo; Among the efficient therapies, lenalidomide-carfilzomib was significantly superior to lenalidomide (OR ranged from 2.18 to 2.20), daratumumab (OR ranged from 1.49 to 2.66) and ixazomib (OR ranged from 2.75 to 3.57).
CONCLUSION
Considering OS and PFS, lenalidomide-carfilzomib should be recommended as the best therapy. In clinical practice, this must be weighed against the increased risk of adverse events and financial burden. However, more head-to-head studies are needed to confirm these findings.
Topics: Antineoplastic Combined Chemotherapy Protocols; Boron Compounds; Bortezomib; Glycine; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Prednisone; Thalidomide
PubMed: 36125238
DOI: 10.1080/16078454.2022.2121900 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2022Tumor necrosis factor alpha (TNF-α) is a cytokine with a key role in proinflammation and multiple diseases, including cancer. The gene encoding TNF-α is located within... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Tumor necrosis factor alpha (TNF-α) is a cytokine with a key role in proinflammation and multiple diseases, including cancer. The gene encoding TNF-α is located within a highly polymorphic region on chromosome 6p21.3; two polymorphisms -308G/A (rs1800629) and -238G/A (rs361525) have been associated with occurrence of human diseases. There is a debate in recent meta-analyses that reached discrepant conclusions regarding the potential role of TNF-α polymorphisms in multiple myeloma (MM) risk. The aim of this systematic review and meta-analysis is to investigate the association between the aforementioned two polymorphisms with the risk and survival of MM.
MATERIALS AND METHODS
Eligible articles were identified through an extensive search in PubMed database (end of search: June 18, 2020). The pooled effect estimates were calculated following the random-effects models by Der Simonian and Laird. Separate analyses were conducted by ethnicity. Between-study heterogeneity was quantified, and the deviation of genotype frequencies in controls from the Hardy-Weinberg equilibrium was evaluated.
RESULTS
Eighteen studies (2934 cases, 4291 controls) have been included in the quantitative synthesis examining risk and 5 studies for survival (557 cases). No association was found between -308G/A and -238G/A TNF-α polymorphisms and MM susceptibility in all genetic models for both Caucasian and East Asian populations. There was no association between -308G/A and -238G/A TNF-α polymorphisms and survival (overall or progression-free) of MM.
CONCLUSION
This systematic review and meta-analysis did not reveal a significant effect of -308G/A and -238G/A TNF-α polymorphisms upon risk or survival of MM.
Topics: Asian People; Case-Control Studies; Genetic Predisposition to Disease; Humans; Multiple Myeloma; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha
PubMed: 34642126
DOI: 10.1016/j.clml.2021.08.010 -
Leukemia & Lymphoma Jan 2017In newly diagnosed multiple myeloma (MM), patients ineligible for front-line autologous stem cell transplantation (ASCT), melphalan and prednisone (MP) with thalidomide... (Meta-Analysis)
Meta-Analysis Review
In newly diagnosed multiple myeloma (MM), patients ineligible for front-line autologous stem cell transplantation (ASCT), melphalan and prednisone (MP) with thalidomide (MPT) or bortezomib (VMP) are standard first-line therapeutic options. Despite new treatment regimens incorporating bortezomib or lenalidomide, MM remains incurable. The FIRST study demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) for the combination of lenalidomide and low-dose dexamethasone (Rd) until progression vs. MPT in transplant-ineligible ndMM patients. However, to date no head-to-head randomized controlled trials (RCTs) have compared Rd or MPT versus VMP. We conducted a network meta-analysis using RCTs identified through a systematic literature review to evaluate the relative efficacy of Rd versus other regimens on survival endpoints in previously untreated MM patients ineligible for ASCT. In this analysis, Rd was associated with a significant PFS and survival advantage versus other first-line treatments (VMP, MPT, MP), challenging the role of alkylators in this setting.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Multiple Myeloma; Neoplasm Staging; Publication Bias; Survival Analysis; Treatment Outcome
PubMed: 27124703
DOI: 10.1080/10428194.2016.1177772 -
Current Oncology (Toronto, Ont.) May 2023Multiple myeloma usually affects older adults. However, younger patients constitute a significant subset as approximately 10% of cases occur in subjects younger than 50... (Review)
Review
Multiple myeloma usually affects older adults. However, younger patients constitute a significant subset as approximately 10% of cases occur in subjects younger than 50 years old. Young patients, who are underrepresented in the literature, are diagnosed during their most productive years of life, urging the need for tailored treatment approaches. This literature review aims to report recent studies specifically addressing young patients with a focus on characteristics at diagnosis, cytogenetics, treatments, and outcomes. We searched PubMed for studies involving young patients with multiple myeloma ≤50 years old. The time span of our literature review search was from 1 January 2010 to 31 December 2022. Overall, 16 retrospective studies were analyzed for this review. Young patients with multiple myeloma tend to have less advanced disease, more frequent light chain subtypes, and survive longer compared to their older counterparts. However, available studies included a limited number of patients; the newest revised international staging system was not used to stratify patients, cytogenetics varied from one cohort to another, and most patients did not receive contemporary triplet/quadruplet treatments. This review emphasizes the need to perform contemporary, large-scale retrospective studies to improve knowledge regarding the presentation and outcomes of young myeloma patients in the era of modern treatments.
Topics: Humans; Aged; Middle Aged; Multiple Myeloma; Retrospective Studies
PubMed: 37366879
DOI: 10.3390/curroncol30060396 -
Health Technology Assessment... Dec 2011Multiple myeloma (MM) is the second most common haematological cancer in the UK. MM is not curable but can be treated with a combination of supportive measures and... (Review)
Review
The clinical effectiveness and cost-effectiveness of bortezomib and thalidomide in combination regimens with an alkylating agent and a corticosteroid for the first-line treatment of multiple myeloma: a systematic review and economic evaluation.
BACKGROUND
Multiple myeloma (MM) is the second most common haematological cancer in the UK. MM is not curable but can be treated with a combination of supportive measures and chemotherapy that aim to extend the duration and quality of survival. The majority of patients are not able to withstand intensive treatment, such as high-dose chemotherapy with autologous stem cell transplantation (SCT), and so they are offered single-agent or combination chemotherapy. Combination therapies typically include chemotherapy with an alkylating agent and a corticosteroid. More recently, combination therapies have incorporated drugs such as thalidomide (Thalidomide Celgene®, Celgene) and bortezomib (Velcade®, Janssen-Cilag).
OBJECTIVE
To assess the clinical effectiveness and cost-effectiveness of bortezomib or thalidomide in combination chemotherapy regimens with an alkylating agent and a corticosteroid for the first-line treatment of MM.
DATA SOURCES
Electronic bibliographic databases, including MEDLINE, EMBASE and The Cochrane Library, were searched from 1999 to 2009 for English-language articles. Bibliographies of articles, grey literature sources and manufacturers' submissions were also searched. Experts in the field were asked to identify additional published and unpublished references.
REVIEW METHODS
Titles and abstracts were screened for eligibility by two reviewers independently. The inclusion criteria specified in the protocol were applied to the full text of retrieved papers by one reviewer and checked independently by a second reviewer. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Differences in opinion were resolved through discussion at each stage. A cost-utility decision-analytic model was used to compare the cost-effectiveness estimates of bortezomib in combination with melphalan and prednisolone/prednisone (VMP), thalidomide in combination with cyclophosphamide and attenuated dexamethasone (CTDa), and thalidomide in combination with melphalan and prednisolone/prednisone (MPT) versus melphalan and prednisolone/prednisone (MP).
RESULTS
A total of 1436 records were screened and 40 references were retrieved for the systematic review of clinical effectiveness. Five randomised controlled trials (RCTs) met the inclusion criteria for the review: one RCT evaluated VMP, three evaluated MPT and one evaluated CTDa. The comparator in all of the included trials was MP. The review found that VMP and MPT can both be considered more clinically effective than MP for the first-line treatment of MM in people for whom high-dose therapy and SCT would not be appropriate. CTDa was more effective than MP in terms of complete response but data on survival outcomes did not meet the inclusion criteria. Cost-effectiveness analysis indicated that MPT has a greater probability of being cost-effective than either VMP or CTDa.
LIMITATIONS
For most RCTs, details needed to judge study quality were incompletely reported. All studies stated that the analyses followed intention-to-treat principles but none adequately reported data censoring. Only one RCT contributed data on VMP and the published peer-reviewed follow-up data were immature. For MPT, overall survival data from two trials were eligible for inclusion but the doses of thalidomide differed between the trials and the treatment period was not reflective of current UK practice so the generalisability of the findings was uncertain. Two RCTs had a maintenance phase with thalidomide that did not meet the inclusion criteria so some of these results were not eligible for the review. Limited evidence on health-related quality of life (HRQoL) was provided by the single trial of VMP versus MP.
CONCLUSIONS
Service provision is unlikely to change greatly. As uncertainties remain, further research is needed regarding the use of bortezomib- and thalidomide-containing combination regimens. Head-to-head trials of bortezomib- and thalidomide-containing combination regimes are required, including assessments of patient HRQoL in response to treatment.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adrenal Cortex Hormones; Alkylating Agents; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Cost-Benefit Analysis; Cyclophosphamide; Humans; Immunosuppressive Agents; Melphalan; Multiple Myeloma; Pyrazines; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Survival Analysis; Thalidomide
PubMed: 22146234
DOI: 10.3310/hta15410 -
Scientific Reports Jun 2016During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer... (Meta-Analysis)
Meta-Analysis Review
During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer relapsing. Thus, novel therapeutic agents are needed. We aimed to assess the efficacy and safety of a novel agent panobinostat for patients with relapsed or/and refractory MM. A systematic literature review identified studies for clinical trials about panobinostat in patients with relapsed or/and refractory MM. We searched studies published between January 2000 and December 2015 in Pubmed, Ovid, EBSCO and the Cochrane library. Random-effect pooled estimates were calculated for overall response rate and rates of common adverse effects. The results showed 11 clinical trials including 700 patients with relapsed or/and refractory MM treated with panobinostat were identified. The ORR varied between 0.08 and 0.67. Pooled analyses showed the results that the ORR was 0.45 (95% CI: 0.31-0.59, I(2) = 90.5%, P = 0.000) for panobinostat combined with any other kind of drugs. The most common Grade3/4 adverse effects were thrombocytopenia, neutropenia, lymphopenia, anemia, diarrhea, fatigue, nausea and so on. In conclusion, based on our analyses, the regimen of panobinostat combining with other agents seems to be well tolerated and efficacious in patients with relapsed or/and refractory MM.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Hydroxamic Acids; Indoles; Multiple Myeloma; Panobinostat; Recurrence; Treatment Outcome
PubMed: 27270478
DOI: 10.1038/srep27361 -
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 -
Leukemia & Lymphoma Sep 2014The purpose of this pooled analysis was to synthesize all available data so as to evaluate the efficacy and safety of lenalidomide in patients with POEMS syndrome.... (Meta-Analysis)
Meta-Analysis Review
The purpose of this pooled analysis was to synthesize all available data so as to evaluate the efficacy and safety of lenalidomide in patients with POEMS syndrome. Eligible articles were identified by a search in MEDLINE and ClinicalTrials.gov databases using a predefined combination. Eligible cases of patients treated in our department were additionally included. Overall, 51 patients were included. The median age of patients was 54.5 years (range: 32-79 years). Lenalidomide was given as first- or second-line treatment in 28.6% and 47.6% of patients, respectively. Hematological responses included complete response in 18.6%, very good partial response in 39.5% and partial response in 37.2% of cases. Vascular endothelial growth factor (VEGF) reduction was reported in all cases. Neuropathy improved in 92.0% of cases and stabilized in 8%. The progression-free survival (PFS) estimate at 12 months was 93.9%. Lenalidomide can represent a safe and effective option for the treatment of patients with POEMS.
Topics: Adult; Aged; Angiogenesis Inhibitors; Humans; Immunologic Factors; Lenalidomide; Middle Aged; POEMS Syndrome; Thalidomide; Treatment Outcome
PubMed: 24295131
DOI: 10.3109/10428194.2013.869329