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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 -
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 -
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 -
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 -
Chest Jul 2023Monocyte distribution width (MDW) is an emerging biomarker for infection. It is available easily and quickly as part of the CBC count, which is performed routinely on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Monocyte distribution width (MDW) is an emerging biomarker for infection. It is available easily and quickly as part of the CBC count, which is performed routinely on hospital admission. The increasing availability and promising results of MDW as a biomarker in sepsis has prompted an expansion of its use to other infectious diseases.
RESEARCH QUESTION
What is the diagnostic performance of MDW across multiple infectious disease outcomes and care settings?
STUDY DESIGN AND METHODS
A systematic review of the diagnostic performance of MDW across multiple infectious disease outcomes was conducted by searching PubMed, Embase, Scopus, and Web of Science through February 4, 2022. Meta-analysis was performed for outcomes with three or more reports identified (sepsis and COVID-19). Diagnostic performance measures were calculated for individual studies with pooled estimates created by linear mixed-effects models.
RESULTS
We identified 29 studies meeting inclusion criteria. Most examined sepsis (19 studies) and COVID-19 (six studies). Pooled estimates of diagnostic performance for sepsis differed by reference standard (Second vs Third International Consensus Definitions for Sepsis and Septic Shock criteria) and tube anticoagulant used and ranged from an area under the receiver operating characteristic curve (AUC) of 0.74 to 0.94, with mean sensitivity of 0.69 to 0.79 and mean specificity of 0.57 to 0.86. For COVID-19, the pooled AUC of MDW was 0.76, mean sensitivity was 0.79, and mean specificity was 0.59.
INTERPRETATION
MDW exhibited good diagnostic performance for sepsis and COVID-19. Diagnostic thresholds for sepsis should be chosen with consideration of reference standard and tube type used.
TRIAL REGISTRY
Prospero; No.: CRD42020210074; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Monocytes; COVID-19; Sepsis; Biomarkers; Communicable Diseases; COVID-19 Testing
PubMed: 36681146
DOI: 10.1016/j.chest.2022.12.049 -
BMC Women's Health Nov 2023The purpose of this systematic review and meta-analysis was to compile existing evidence on the significance of the NLR in predicting endometriosis in order to aid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this systematic review and meta-analysis was to compile existing evidence on the significance of the NLR in predicting endometriosis in order to aid clinical decision-making and outcomes.
METHODS
We searched ProQuest, Web of Science, and PubMed for related studies published before January 2, 2023. Standardized mean difference (SMD) with a 95% confidence interval (CI) was reported for each outcome. Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used Newcastle-Ottawa Scale (NOS) for quality assessment.
RESULTS
Overall, 18 article with were included in the analysis. A random-effect model revealed that patients with endometriosis had elevated levels of NLR compared to healthy controls (SMD = 0.79, 95% CI = 0.33 to 1.25, P < 0.001). Patients with endometriosis had elevated levels of NLR compared to those with other benign tumors (SMD = 0.85, 95% CI = 0.17 to 1.53, P = 0.014). In addition, NLR level of patients with stage III and IV endometriosis was not different from that of patients with stage I and II endometrioma (SMD = 0.30, 95% CI = -0.14 to 0.74, P = 0.18). However, NLR level was not different between endometriosis patients with and without peritoneal lesions (SMD = -0.12, 95% CI = -0.34to 0.10, P = 0.28), between patients with and without endometrioma (SMD = 0.20, 95% CI = -0.15 to 0.55, P = 0.26) and between endometriosis patients with and without deep lesions (SMD = 0.04, 95% CI = -0.20 to 0.28, P = 0.72). The pooled sensitivity of NLR was 0.67 (95% CI = 0.60-0.73), and the pooled specificity was 0.68 (95% CI, 0.62-0.73).
CONCLUSIONS
NLR might be utilized in clinics as a possible predictor to help clinicians diagnose endometriosis in affected women.
Topics: Humans; Female; Endometriosis; Neutrophils; Lymphocytes; Peritoneal Diseases
PubMed: 37936116
DOI: 10.1186/s12905-023-02692-7 -
Frontiers in Immunology 2023Emerging evidence suggests a correlation between the lymphocyte-monocyte ratio (LMR) and the prognosis in patients with gastric cancer (GC) undergoing immune checkpoint... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Emerging evidence suggests a correlation between the lymphocyte-monocyte ratio (LMR) and the prognosis in patients with gastric cancer (GC) undergoing immune checkpoint inhibitor (ICI) therapy. Nevertheless, the existing findings remain contentious.
METHODS
A comprehensive search of literature was conducted in databases including PubMed, Embase, Web of Science, and the Cochrane Library, spanning from the inception of each database to August 30, 2023 to collect studies exploring the interplay between LMR and clinical outcomes. Eligible studies were selected following predefined inclusion and exclusion criteria. Primary outcomes encompassed progression-free survival (PFS) and overall survival (OS), which were estimated using hazard ratios (HR) and corresponding 95% confidence intervals (CI).
RESULTS
Our analysis incorporated eight cohort studies, involving 815 patients. Aggregate data revealed associations between an elevated LMR at baseline and prolonged PFS (HR=0.58; 95% CI: 0.47-0.71, p<0.00001) and improved OS (HR=0.51, 95% CI: 0.33-0.79; p=0.003). Furthermore, LMR exhibited a favorable association with PFS after treatment (HR=0.48; 95% CI: 0.29-0.79; p= 0.004), while such a correlation was not evident in the OS analysis. Importantly, a high level of LMR was associated with prolonged PFS across varying sample sizes, follow-up duration, treatment combinations, line of therapy, and cut-off values.
CONCLUSION
A high pre-treatment LMR is associated with improved OS and PFS in GC patients treated with ICIs. LMR emerges as a potent biomarker for prognostic assessment in these patients, offering valuable insights for informed treatment decisions within the domain of GC immunotherapy.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42021228512.
Topics: Humans; Prognosis; Monocytes; Immune Checkpoint Inhibitors; Stomach Neoplasms; Lymphocytes
PubMed: 38090560
DOI: 10.3389/fimmu.2023.1321584 -
The Journal of Maternal-fetal &... Dec 2023Using straightforward and accessible haematological parameters platelet/lymphocyte ratio (PLR) to diagnose preeclampsia (PE) early and precisely remains a challenge.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Using straightforward and accessible haematological parameters platelet/lymphocyte ratio (PLR) to diagnose preeclampsia (PE) early and precisely remains a challenge. Although several clinical studies suggested that PLR is able to diagnose PE, there has been no systematic evaluation of the diagnostic utility.
OBJECTIVES
To examine the diagnostic accuracy and potential applicability of PLR in the detection of PE.
STUDY DESIGN
Seven databases were searched using a combination of PLR and PE terms, and all potentially pertinent studies were systematically searched up to March 2023. All potentially relevant studies both prospective and retrospective were reviewed. To assess the diagnostic value of PLR for PE, pooled sensitivity (Sen), specificity (Spe), diagnostic odds ratio (DOR) and area under the summary receiver operating characteristic curve (SROC-AUC) were calculated.
RESULTS
Thirteen studies were enrolled in the meta-analysis. In the second and third trimesters, the PLR suggested a diagnostic value for PE with a pooled Sen of 54.7% [95% confidence interval (CI) (51.7, 57.6)], Spe of 77.8% [95% CI (75.5, 80.0)], + LR of 2.457 [95% CI (1.897, 3.182)], -LR of 0.584 [95% CI (0.491, 0.695)], DOR of 4.434 [95% CI (3.071, 6.402)], the SROC-AUC of 0.7296 and the standard error (SE) of 0.0370.
CONCLUSION
For the diagnosis of PE, PLR has a limited sensitivity but an acceptable specificity, and showed moderate accuracy. Further using complete blood count (CBC) indicators such as PLR alone or in combination to diagnose and predict PE could reduce healthcare costs and improve maternal and child prognosis.
Topics: Child; Female; Humans; Pregnancy; Lymphocytes; Pre-Eclampsia; Prospective Studies; Retrospective Studies; ROC Curve; Sensitivity and Specificity
PubMed: 37455131
DOI: 10.1080/14767058.2023.2234540 -
Cancer Medicine Sep 2023The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta-analysis to estimate their predictive significance.
METHODS
A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included.
RESULTS
Seventeen studies reporting sufficient data met the inclusion criteria for meta-analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD-L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD-L1 and CTLA-4 were not correlated to the treatment response.
CONCLUSION
This meta-analysis indicated that high-density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer.
Topics: Humans; B7-H1 Antigen; Neoadjuvant Therapy; CD8-Positive T-Lymphocytes; Biomarkers; Rectal Neoplasms; Biopsy; Lymphocytes, Tumor-Infiltrating; Prognosis
PubMed: 37537787
DOI: 10.1002/cam4.6423