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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 -
Transplantation and Cellular Therapy Jan 2024Chimeric antigen receptor T cell (CAR-T) therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), are innovative treatments for patients... (Meta-Analysis)
Meta-Analysis
Chimeric antigen receptor T cell (CAR-T) therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), are innovative treatments for patients with relapsed or refractory (r/r) large B cell lymphoma (LBCL). Following initial regulatory approvals, real-world evidence (RWE) of clinical outcomes with these therapies has been accumulating rapidly. Notably, several large registry studies have been published recently. Here we comprehensively describe clinical outcomes with approved CAR-T therapies in patients with r/r LBCL using available RWE. We systematically searched Embase, MEDLINE, and 15 conference proceedings to identify studies published between 2017 and July 2022 that included ≥10 patients with r/r LBCL treated with commercially available CAR-T therapies. Eligible study designs were retrospective or prospective observational studies. Key outcomes of interest were objective response rate (ORR), complete response (CR) rate, overall survival (OS), progression-free survival (PFS), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Random-effects meta-analyses were used to compare real-world outcomes with those of pivotal clinical trials and to compare clinical outcomes associated with axi-cel and tisa-cel. Study cohort mapping was conducted to avoid including patients more than once. Of 76 cohorts we identified, 46 reported patients treated specifically with either axi-cel or tisa-cel, with 39 cohorts (n = 2754 patients) including axi-cel and 20 (n = 1649) including tisa-cel. No studies of liso-cel that met the inclusion criteria were identified during the search period. One-half of the tisa-cel cohorts were European, compared with 33% of the axi-cel cohorts. Among studies with available data, axi-cel had a significantly shorter median time from apheresis to CAR-T infusion than tisa-cel. Despite including broader patient populations, real-world effectiveness and safety of both axi-cel and tisa-cel were consistent with data from the pivotal clinical trials. Comparative meta-analysis of axi-cel versus tisa-cel demonstrated adjusted hazard ratios for OS and PFS of .60 (95% confidence interval [CI], .47 to .77) and .67 (95% CI, .57 to .78), respectively, both in favor of axi-cel. Odds ratios (ORs) for ORR and CR rate, both favoring axi-cel over tisa-cel, were 2.05 (95% CI, 1.76 to 2.40) and 1.70 (95% CI, 1.46 to 1.96), respectively. The probability of grade ≥3 CRS was comparable with axi-cel and tisa-cel, whereas axi-cel was associated with a higher incidence of grade ≥3 ICANS (OR, 3.95; 95% CI, 3.05 to 5.11). Our meta-analysis indicates that CAR-T therapies have manageable safety profiles and are effective in a wide range of patients with r/r LBCL, and that axi-cel is associated with improved OS and PFS and increased risk of grade ≥3 ICANS compared with tisa-cel. Limitations of this study include nonrandomized treatments, potential unknown prognostic factors, and the lack of available real-world data for liso-cel.
Topics: Humans; Cytokine Release Syndrome; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Neurotoxicity Syndromes; Observational Studies as Topic; Pathologic Complete Response; Receptors, Chimeric Antigen; Retrospective Studies; T-Lymphocytes
PubMed: 37890589
DOI: 10.1016/j.jtct.2023.10.017 -
Archives of Dermatological Research Feb 2024Psoriasis is a chronic, inflammatory skin disorder characterized by well-demarcated erythematous lesions with surface scaling. The disease is underpinned by a... (Meta-Analysis)
Meta-Analysis Review
Psoriasis is a chronic, inflammatory skin disorder characterized by well-demarcated erythematous lesions with surface scaling. The disease is underpinned by a dysregulated immune response with a shift in the balance of neutrophils, lymphocytes and platelets. We sought to evaluate the novel systemic inflammatory markers, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as psoriatic indicators. Pubmed, Web of Science and Scopus were systematically searched for relevant studies. Twenty-four studies consisting of a total of 2,275 psoriatic patients (1,301 males and 974 females) and 2,334 healthy controls (1,401 males and 933 females) were identified for inclusion in the quantitative analysis. The NLR and PLR were found to be significantly increased in psoriatic patients [standardized mean difference (SMD) = 0.68, 95% CI 0.56-0.80, p < 0.01, and SMD = 0.37, 95% CI 0.14-0.60, p < 0.01, respectively]. However, no association between the NLR and PLR with psoriasis severity was detected (p = 0.93, and p = 0.83, respectively). In conclusion, the NLR and PLR are simple and cost-effective markers of psoriatic presence, but their value as severity markers requires further study.
Topics: Humans; Female; Male; Neutrophils; Psoriasis; Skin; Lymphocytes
PubMed: 38329632
DOI: 10.1007/s00403-024-02823-6 -
Asian Pacific Journal of Cancer... Dec 2023Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be...
INTRODUCTION
Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management.
METHOD
We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies.
RESULTS
A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue.
CONCLUSION
The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.
Topics: Adult; Humans; Child; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; B-Lymphocytes; Fatigue
PubMed: 38156834
DOI: 10.31557/APJCP.2023.24.12.4025 -
Reviews in Endocrine & Metabolic... Dec 2023Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid tumors. However, the role of inflammation markers in differentiated thyroid carcinoma (DTC) is still uncertain.
OBJECTIVE
This meta-analysis aimed to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with DTC.
METHODS
Studies investigating the association between survival and preoperative circulating inflammatory markers in DTC patients were included. The primary outcome was disease-free survival (DFS). Cumulative logarithms of the hazard ratio (log-HRs) with 95% CI were calculated through the inverse variance method using a random-effects model.
RESULTS
A total of 7599 patients with a mean age of 48.89 (95% CI 44.16-53.63) were included. The estimated pooled log-HRs for DFS were 0.07 for NLR (95% CI -0.12-0.26; p = 0.43), -0.58 for LMR (95% CI -1.21-0.05; p = 0.06), and 0.01 (95% CI 0-0.01; p = 0.21) for PLR.
CONCLUSIONS
Our meta-analysis showed no association between NLR, PLR, LMR and DFS in DTC; however, more prospective data are needed to better define the association between inflammatory status and prognosis of DTC.
Topics: Humans; Middle Aged; Prognosis; Prospective Studies; Lymphocytes; Inflammation; Thyroid Neoplasms
PubMed: 37828383
DOI: 10.1007/s11154-023-09845-x -
Inflammation Research : Official... May 2024γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells,... (Review)
Review
OBJECTIVE
γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells, thereby modulating immune responses. As the first line of host defense, γδ T cells are essential for mucosal homeostasis and immune surveillance. When abnormally activated or impaired, γδ T cells can contribute to pathogenic processes. Accumulating evidence has revealed substantial impacts of γδ T cells on the pathogenesis of cancers, infections, and immune-inflammatory diseases. γδ T cells exhibit dual roles in cancers, promoting or inhibiting tumor growth, depending on their phenotypes and the clinical stage of cancers. During infections, γδ T cells exert high cytotoxic activity in infectious diseases, which is essential for combating bacterial and viral infections by recognizing foreign antigens and activating other immune cells. γδ T cells are also implicated in the onset and progression of immune-inflammatory diseases. However, the specific involvement and underlying mechanisms of γδ T cells in oral diseases have not been systematically discussed.
METHODS
We conducted a systematic literature review using the PubMed/MEDLINE databases to identify and analyze relevant literature on the roles of γδ T cells in oral diseases.
RESULTS
The literature review revealed that γδ T cells play a pivotal role in maintaining oral mucosal homeostasis and are involved in the pathogenesis of oral cancers, periodontal diseases, graft-versus-host disease (GVHD), oral lichen planus (OLP), and oral candidiasis. γδ T cells mainly influence various pathophysiological processes, such as anti-tumor activity, eradication of infection, and immune response regulation.
CONCLUSION
This review focuses on the involvement of γδ T cells in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which γδ T cells influence the pathogenesis and progression of these conditions. This review underscores the potential of γδ T cells as therapeutic targets in managing oral health issues.
Topics: Humans; Mouth Diseases; Animals; Receptors, Antigen, T-Cell, gamma-delta; Intraepithelial Lymphocytes; Graft vs Host Disease; T-Lymphocytes
PubMed: 38563967
DOI: 10.1007/s00011-024-01870-z -
BMC Infectious Diseases Nov 2023The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis.
METHODS
PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022.
RESULTS
Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14-2.48, P-value < 0.001) in either prospective (SMD = 2.38, 95% CI = 1.40-3.35, P-value < 0.001) or retrospective studies (SMD = 0.87, 95% CI = 0.63-1.12, P-value < 0.001) with a pooled sensitivity of 79% (95% CI = 62-90%), and a pooled specificity of 91% (95% CI = 73-97%). Also, we found that NLR is higher in neonates with sepsis compared to those who were suspected of sepsis but eventually had negative blood cultures (SMD =1.99, 95% CI = 0.76-3.22, P-value = 0.002) with a pooled sensitivity of 0.79% (95% CI = 0.69-0.86%), and a pooled specificity of 73% (95% CI = 54-85%). In addition, neonates with sepsis had elevated levels of NLR compared to other ICU admitted neonates (SMD = 0.73, 95% CI = 0.63-0.84, P < 0.001). The pooled sensitivity was 0.65 (95% CI, 0.55-0.80), and the pooled specificity was 0.80 (95% CI, 0.68-0.88).
CONCLUSION
Our findings support NLR as a promising biomarker that can be readily integrated into clinical settings to aid in diagnosing neonatal sepsis. As evidenced by our results, restoring balance to the innate and adaptive immune system may serve as attractive therapeutic targets. Theoretically, a reduction in NLR values could be used to measure therapeutic efficacy, reflecting the restoration of balance within these systems.
Topics: Infant, Newborn; Humans; Neutrophils; Neonatal Sepsis; Retrospective Studies; Prospective Studies; Lymphocytes; Biomarkers; Sepsis
PubMed: 38012554
DOI: 10.1186/s12879-023-08800-0 -
Clinical Biochemistry Nov 2023Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of more than 30 dB in less than 72 h. SSNHL is a frequent complaint and an emergency in... (Meta-Analysis)
Meta-Analysis Review
Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of more than 30 dB in less than 72 h. SSNHL is a frequent complaint and an emergency in otolaryngology. Various biomarkers have been used to determine the prognosis of SSNHL. This systematic review and meta-analysis aims to evaluate the relationship between the different biomarkers and the prognosis of SSNHL. We searched English-language literature up to October 2022 in four databases, including PubMed, Google Scholar, Cochrane, and Science Direct. This search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study was reported in the International Prospective Register of Systematic Reviews (PROSPERO) database (ID = CRD42022369538). All studies examining the role of neutrophil to lymphocyte ratio (NLR) concluded that higher NLR is associated with a worse prognosis. The results of studies regarding the relationship between platelet to lymphocyte ratio (PLR) and tumor necrosis factor (TNF) are controversial. Other factors shown to be associated with SSNHL include Glycated hemoglobin (HbA1C), blood glucose, iron levels, serum endocan, salusin-beta, and bone turnover biomarkers. This meta-analysis showed that PLR, NLR, and neutrophils were significantly different between recovered and non-recovered patients. PLR, NLR, and neutrophil count are reliable tools to assess the prognosis of patients with SSNHL.
Topics: Humans; Biomarkers; Hearing Loss, Sensorineural; Hearing Loss, Sudden; Lymphocytes; Neutrophils; Prognosis
PubMed: 37944628
DOI: 10.1016/j.clinbiochem.2023.110684 -
Frontiers in Immunology 2023Endometriosis is a chronic disease affecting 6-10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood...
BACKGROUND
Endometriosis is a chronic disease affecting 6-10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in lesion clearance in other pathologies, yet their function in endometriosis is unknown. We systematically evaluated the literature on the CD8 T in peripheral blood and endometriosis-associated tissues to determine the current understanding of their pathophysiological and clinical relevance in the disease and associated conditions (e.g. infertility and pelvic pain).
METHODS
Four databases were searched (MEDLINE, EMBASE, Web of Science, CINAHL), from database inception until September 2022, for papers written in the English language with database-specific relevant terms/free-text terms from two categories: CD8 T cells and endometriosis. We included peer-reviewed papers investigating CD8 T cells in peripheral blood and endometriosis-associated tissues of patients with surgically confirmed endometriosis between menarche and menopause, and animal models with oestrous cycles. Studies enrolling participants with other gynaecological pathologies (except uterine fibroids and tubal factor infertility used as controls), cancer, immune diseases, or taking immune or hormonal therapy were excluded.
RESULTS
28 published case-control studies and gene set analyses investigating CD8 T cells in endometriosis were included. Data consistently indicate that CD8 T cells are enriched in endometriotic lesions in comparison to eutopic endometrium, with no differences in peripheral blood CD8 T populations between patients and healthy controls. Evidence on CD8 T cells in peritoneal fluid and eutopic endometrium is conflicting. CD8 T cell cytotoxicity was increased in the menstrual effluent of patients, and genomic analyses have shown a clear trend of enriched CD8 T effector memory cells in the eutopic endometrium of patients.
CONCLUSION
Literature on CD8 T cells in endometriosis-associated tissues is inconsistent. Increased CD8 T levels are found in endometriotic lesions, however, their activation potential is understudied in all relevant tissues. Future research should focus on identifying clinically relevant phenotypes to support the development of non-invasive diagnostic and treatment strategies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier CRD42021233304.
Topics: Humans; Animals; Female; Endometriosis; Endometrium; CD8-Positive T-Lymphocytes; Infertility; Pelvic Pain
PubMed: 37497226
DOI: 10.3389/fimmu.2023.1225639 -
Clinical and Experimental Medicine Oct 2023As a novel anticancer therapy, chimeric antigen receptor T (CAR T) cell therapy may lead to cardiotoxic reactions. However, the exact incidence remains unclear. Our... (Meta-Analysis)
Meta-Analysis Review
As a novel anticancer therapy, chimeric antigen receptor T (CAR T) cell therapy may lead to cardiotoxic reactions. However, the exact incidence remains unclear. Our study aimed to preliminarily assess the prevalence of cardiotoxicity after CAR T cell treatment using a systematic review and meta-analysis. PubMed, Embase, Web of Science, and Cochrane databases were searched for potentially relevant studies. All types of relevant clinical studies were screened and assessed for risk bias. In most instances, random-effect models were used for data analysis, and heterogeneity between studies was evaluated. Standard quality assessment tools were used to assess quality. The study was registered with PROSPERO (CRD42022304611). Eight eligible studies comprising 3567 patients, including seven observational studies and one controlled study, were identified. The incidence of cardiovascular events was 16.7% [95% confidence interval (CI) 0.138-0.200, P < 0.01)]. Arrhythmia was the most common disorder, with an incidence of 6.5% (95% CI 0.029-0.115, P < 0.01). The occurrence of cardiotoxicity was associated with cytokine release syndrome (CRS), with a prevalence of 18.7% (95% CI 0.107-0.315, P < 0.01). Moreover, such adverse reactions were more common when CRS > 2 (OR = 0.07, 95% CI 0.02-0.29, P < 0.01). The risk of cardiotoxicity was not notably higher in patients receiving CAR T cell therapy than in those receiving traditional anticancer treatment. However, sufficient attention should be paid to this. And further evidence from large-scale clinical trials are needed.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Cardiotoxicity; T-Lymphocytes; Cytokine Release Syndrome; Cell- and Tissue-Based Therapy
PubMed: 36930381
DOI: 10.1007/s10238-023-01042-z