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JAMA Pediatrics Aug 2022Neonatal early-onset sepsis (EOS) is a severe disease, particularly in preterm infants. Timely diagnosis can be challenging owing to unspecific presentation and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Neonatal early-onset sepsis (EOS) is a severe disease, particularly in preterm infants. Timely diagnosis can be challenging owing to unspecific presentation and questionable performance of the common markers of infection. Presepsin was recently proven to be a promising biomarker for the diagnosis of EOS.
OBJECTIVE
To assess presepsin accuracy for the diagnosis of EOS.
DATA SOURCES
PubMed Medline, EMBASE, Web of Science, and Google Scholar. No publication date restrictions were applied. The literature search was limited to the English language. Articles were checked for duplication.
STUDY SELECTION
Inclusion criteria were studies that (1) included term or preterm newborns (defined as newborns with gestational age ≥37 weeks or <37 weeks, respectively); (2) included a diagnosis of EOS, defined as culture-proven sepsis for primary analysis and as either clinical or culture-proven sepsis for secondary analysis; and (3) assessed presepsin values during the initial workup for suspected EOS. Exclusion criteria were studies that (1) did not include EOS cases; (2) lacked data on presepsin sensitivity and/or specificity; and (3) were case reports, commentaries, or reviews. Two independent reviewers performed the study selection.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers performed data extraction and quality assessment. Quality assessment was performed using the Quality Assessment for Studies of Diagnostic Accuracy 2 tool, and data were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
The outcomes of interest for both the primary and secondary analyses were presepsin sensitivity, specificity, and diagnostic odds ratio for the diagnosis of EOS.
RESULTS
A total of 12 studies of 245 (4.9%) met inclusion criteria for the primary analysis. Twenty-three studies of 245 (9.4%) met the inclusion criteria for the secondary analysis. In the primary analysis, among 12 studies and 828 newborns of any gestational age, pooled sensitivity and specificity were 0.93 (95% CI, 0.86-0.95) and 0.91 (95% CI, 0.85-0.95), respectively; pooled diagnostic odds ratio was 131.69 (95% CI, 54.93-310.94). Subgroup analysis showed that presepsin specificity was associated with the inclusion of only EOS or all neonatal sepsis. Presepsin accuracy was not associated with gestational age, measurement with chemiluminescence enzyme immunoassay or enzyme-linked immunosorbent assay testing, country where the study was performed, or risk of bias judgment. In the secondary analysis, among 23 studies and 1866 newborns, accuracy was significantly associated with only test type.
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that presepsin was an accurate biomarker of EOS. Clinical trials are warranted to assess its usefulness and safety to reduce early antibiotic exposure, particularly in preterm newborns.
Topics: Biomarkers; Humans; Infant; Infant, Newborn; Infant, Premature; Lipopolysaccharide Receptors; Neonatal Sepsis; Peptide Fragments; Sepsis
PubMed: 35639395
DOI: 10.1001/jamapediatrics.2022.1647 -
Chest Aug 2017Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are... (Meta-Analysis)
Meta-Analysis Review
Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials.
BACKGROUND
Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use.
METHODS
MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors and between treatment naive and previously treated patients.
RESULTS
Nineteen trials (12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%; 95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P = .001). PD-1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs 2.8%; 95% CI, 1.7%- 4%; P = .03).
CONCLUSIONS
There was a higher incidence of pneumonitis with use of PD-1 inhibitors compared with PD-L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients.
Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Humans; Immunotherapy; Lung Neoplasms; Male; Middle Aged; Nivolumab; Pneumonia; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 28499515
DOI: 10.1016/j.chest.2017.04.177 -
The Lancet. Oncology Sep 2021Numerous ongoing trials are testing anti-PD-1-based or anti-PD-L1-based cancer treatment combinations. Understanding the toxicity profiles of treatment-related adverse... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous ongoing trials are testing anti-PD-1-based or anti-PD-L1-based cancer treatment combinations. Understanding the toxicity profiles of treatment-related adverse events is essential. The aim of this study was to comprehensively investigate the incidences and profiles of treatment-related adverse events across different combination therapies.
METHODS
We did a systematic review and meta-analysis comparing different chemotherapy, targeted therapy, immunotherapy, and radiotherapy combinations with PD-1 or PD-L1 inhibitors. We searched Pubmed, Embase, and Cochrane databases for articles published in English between Jan 1, 2000, and May 21, 2020, investigating globally approved PD-1 or PD-L1 inhibitor-based combination therapies. Only prospective trials reporting overall incidence or tabulated data of treatment-related adverse events were included. Trials investigating sequential therapies, comprising three or more classes of therapies, and enrolling less than ten patients were excluded. The primary outcomes were overall incidences and profiles for all-grade and grade 3 or higher treatment-related adverse events by random-effect models. Heterogeneity between studies was assessed with I statistics. The summary measures for main outcomes are incidences (95% CI). The 95% CI were calculated together with the incidence through a random-effects model with a logit transformation. The protocol is registered with PROSPERO (CRD42020189617).
FINDINGS
We identified 2540 records, of which 161 studies (17 197 patients) met the inclusion criteria. The overall incidence of treatment-related adverse events in the chemotherapy combination was 97·7% (95% CI 96·4-98·5; I=75%) for all-grade adverse events and 68·3% (60·7-75·0; I=93%) for grade 3 or higher adverse events; in the targeted therapy combination was 94·5% (90·7-96·8; I=86%) for all-grade adverse events and 47·3% (37·3-57·5; I=93%) for grade 3 or higher adverse events; in the immunotherapy combination was 86·8% (80·9-91·1; I=94%) for all-grade adverse events and 35·9% (29·5-42·9; I=92%) for grade 3 or higher adverse events; and in the radiotherapy combination was 89·4% (69·0-96·9; I=74%) for all-grade adverse events and 12·4% (4·4-30·6; I=73%) for grade 3 or higher adverse events. For these four combination therapies, the most common all-grade adverse events were anaemia (45.4% [95% CI 32·4-59·1]), fatigue (34·3% [27·5-41·9]), fatigue (26·4% [19·2-35·2]), and dysphagia (30·0% [18·7-44·5]), respectively, and the most common grade 3 or higher adverse events were neutropenia (19·6% [13·5-27·7]), hypertension (9·3% [5·7-14·9]), lipase increased (7·2% [5·2-9·9]), and lymphopenia (10·3% [4·5-21·8]). All included randomised controlled trials had a low risk of bias.
INTERPRETATION
Our study provides comprehensive data on treatment-related adverse events of different PD-1 or PD-L1 inhibitor-based combination therapies. Our results provide an essential reference of toxicity profiles of PD-1 or PD-L1 inhibitor-based combination therapies for clinicians in routine practice of cancer care.
FUNDING
National Key Research and Development Programme, National Natural Science Foundation of China key program, National Natural Science Foundation of China general program, Chinese Academy of Medical Sciences Initiative for Innovative Medicine, Beijing Municipal Science and Technology Commission, Non-profit Central Research Institute Fund.
Topics: B7-H1 Antigen; Clinical Trials as Topic; Combined Modality Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Incidence; Programmed Cell Death 1 Receptor
PubMed: 34391508
DOI: 10.1016/S1470-2045(21)00333-8 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2021Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis of CD19-Specific CAR-T Cell Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia in the Pediatric and Young Adult Population: Safety and Efficacy Outcomes.
Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of relapsed/refractory (RR) ALL remains a challenge. Even after stem-cell transplantation and intensive chemotherapy, the prognosis of RR-ALL remains grave. The advent of chimeric antigen receptors has demonstrated promising results in RR-ALL. Chimeric antigen receptor-modified T cells (CAR-T) and engineered T cells are used to target cancer cells. In 2017, the US Food and Drug Administration approved CD19-specific CAR-T (tisagenlecleucel) therapy for RR-B-cell ALL in patients under 25 years old. In this systematic review, we discuss the efficacy and safety of CD19-specific CAR-T therapy in RR-B-cell ALL in the pediatric and young adult population. We searched the PubMed, Embase, Web of Science, Cochrane Library, and clinical trials databases. A total of 448 patients received a CD19-specific CAR-T product, and 446 patients had evaluable data. The age range was 0 to 30 years. The incidence rate of complete remission was 82%. The cumulative incidence of relapse after CD19-specific CAR-T therapy is 36%. Similarly, the incidence rate of grade 3 or higher adverse events of neutropenia, thrombocytopenia, neurotoxicity, infections, and cytokine release syndrome were 38%, 23%, 18%, 29%, and 19%, respectively. Our subgroup analysis shows the incidence rate of minimal residual negative complete remission was 69% with the CD28z costimulatory domain, 81% with the 4-1BB domain, and 77% with fourth-generation CD19-specific CAR-T therapy.
Topics: Adolescent; Antigens, CD19; Child; Cytokine Release Syndrome; Drug Resistance, Neoplasm; Humans; Immunotherapy, Adoptive; Neoplasm Recurrence, Local; Neurotoxicity Syndromes; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Remission Induction; Thrombocytopenia; Young Adult
PubMed: 33573914
DOI: 10.1016/j.clml.2020.12.010 -
Cancer Medicine Feb 2021A combination of programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors and radiotherapy (RT) is increasingly being used to treat... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A combination of programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non-small-cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta-analysis to summarize the related research.
METHODS
We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta-analysis.
RESULTS
The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non-combination therapy, combination therapy using PD-1/PD-L1 inhibitors and RT was associated with prolonged overall survival (OS) (1-year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35-2.33, p = 0.000; 2-year OS: OR 1.77, 95% CI 1.35-2.33, p = 0.000) and progression-free survival (PFS) (0.5-year PFS: OR 1.83, 95% CI 1.13-2.98, p = 0.014; 1-year PFS: OR 2.09, 95% CI 1.29-3.38, p = 0.003; 2-year PFS: OR 2.47, 95% CI 1.13-5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06-7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21-2.68, p = 0.004). This meta-analysis showed that compared with non-combination therapy, combination therapy using PD-1/PD-L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1-2 immune-related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD-1/PD-L1 inhibitors followed RT outperformed in which concurrent PD-1/PD-L1 inhibitor and RT followed PD-1/PD-L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD-1/PD-L1 inhibitors may be more effective than a combination of conventional RT with PD-1/PD-L1 inhibitors in patients with advanced NSCLC.
CONCLUSION
Combination therapy using PD-1/PD-L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis.
Topics: B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Combined Modality Therapy; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Programmed Cell Death 1 Receptor; Radiosurgery; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 33465302
DOI: 10.1002/cam4.3718 -
Critical Care (London, England) Nov 2018Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential.
METHOD
Our aim was to compare the diagnostic accuracy of procalcitonin (PCT), C-reactive protein (CRP), procalcitonin combined with C-reactive protein (PCT + CRP) and presepsin in the diagnosis of neonatal sepsis. We searched seven databases to identify studies that met the inclusion criteria. Two independent reviewers performed data extraction. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), and corresponding 95% credible interval (95% CI) were calculated by true positive (TP), false positive (FP), false negative (FN), and true negative (TN) classification using a bivariate regression model in STATA 14.0 software. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, and corresponding 95% CI were the primary outcomes. Secondary outcomes included the sensitivity and specificity in multiple subgroup analyses.
RESULTS
A total of 28 studies enrolling 2661 patients were included in our meta-analysis. The pooled sensitivity of CRP (0.71 (0.63, 0.78)) was weaker than that of PCT (0.85 (0.79, 0.89)), PCT + CRP (0.91 (0.84, 0.95)) and presepsin (0.94 (0.80, 0.99)) and the pooled NLR of presepsin (0.06 (0.02, 0.23)) and PCT + CRP (0.10 (0.05, 0.19)) were less than CRP (0.33 (0.26, 0.42)), and the AUC for presepsin (0.99 (0.98, 1.00)) was greater than PCT + CRP (0.96 (0.93, 0.97)), CRP (0.85 (0.82, 0.88)) and PCT (0.91 (0.89, 0.94)). The results of the subgroup analysis showed that 0.5-2 ng/mL may be the appropriate cutoff interval for PCT. A cut-off value > 10 mg/L for CRP had high sensitivity and specificity.
CONCLUSIONS
The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis. However, further studies are required to confirm these findings.
Topics: Area Under Curve; Biomarkers; C-Reactive Protein; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lipopolysaccharide Receptors; Neonatal Sepsis; Odds Ratio; Pediatrics; Peptide Fragments; Procalcitonin; ROC Curve
PubMed: 30463590
DOI: 10.1186/s13054-018-2236-1 -
Transfusion Medicine Reviews Apr 2019Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize... (Meta-Analysis)
Meta-Analysis
Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize the efficacy and safety of CAR-T cell therapy in patients with relapsed or refractory hematologic or solid malignancies. MEDLINE, Embase, and the Cochrane Register of Controlled Trials (inception - November 21, 2017). Interventional studies investigating CAR-T cell therapy in patients with malignancies were included. Our primary outcome of interest was complete response (defined as the absence of detectable cancer). Two independent reviewers extracted relevant data, assessed risk of bias, and graded the quality of evidence using established methods. A total of 42 hematological malignancy studies and 18 solid tumor studies met were included (913 participants). Of 486 evaluable hematologic patients, 54.4% [95% CI, 42.5%-65.9%] experienced complete response in 27 CD19 CAR-T cell therapy studies. Of 65 evaluable hematologic patients, 24.4% [95% CI, 9.4%-50.3%] experienced complete response in seven non-CD19 CAR-T cell therapy studies. Cytokine release syndrome was experienced by 55.3% [95% CI, 40.3%-69.4%] of patients and neurotoxicity 37.2% [95% CI, 28.6%-46.8%] of patients with hematologic malignancies. Of 86 evaluable solid tumor patients, 4.1% [95% CI, 1.6%-10.6%] experienced complete response in eight CAR-T cell therapy studies. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. There was a strong signal for efficacy of CAR-T cell therapy in patients with CD19+ hematologic malignancies and no overall signal in solid tumor trials published to date. These results will help inform patients, physicians, and other stakeholders of the benefits and risks associated with CAR-T cell therapy.
Topics: Antigens, CD19; Hematologic Neoplasms; Humans; Immunotherapy; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Risk Assessment; T-Lymphocytes; Treatment Outcome
PubMed: 30948292
DOI: 10.1016/j.tmrv.2019.01.005 -
JAMA Oncology Mar 2020Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice.
OBJECTIVE
To assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types.
DATA SOURCES
Systematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to March 1, 2019. In addition, abstracts and presentations from all major conference proceedings were reviewed.
STUDY SELECTION
All randomized clinical trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with cancer were selected as candidates. Retrospective studies, single-arm phase 1/2 studies, and trials comparing anti-PD-1 and anti-PD-L1 with other immunotherapies were excluded. Studies of anti-PD-1 and anti-PD-L1 therapy were screened and paired by the matching of clinical characteristics as mirror groups.
DATA EXTRACTION AND SYNTHESIS
Three investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Trial names, first author, year of publication, study design, National Clinical Trial identifier number, blinding status, study phase, pathologic characteristics, number of patients, patients' age and sex distribution, Eastern Cooperative Oncology Group Performance Status, lines of treatment, study drugs, biomarker status, follow-up time, incidence of adverse events, and hazard ratios (HRs) with 95% CIs for overall survival and progression-free survival were extracted. A random-effects model was applied for data analysis.
MAIN OUTCOMES AND MEASURES
Differences in OS between anti-PD-1 and anti-PD-L1 across different cancer types were assessed. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model.
RESULTS
Nineteen randomized clinical trials involving 11 379 patients were included in the meta-analysis. Overall, anti-PD-1 exhibited superior overall survival (HR, 0.75; 95% CI, 0.65-0.86; P < .001) and progression-free survival (HR, 0.73; 95% CI, 0.56-0.96; P = .02) compared with anti-PD-L1. No significant difference was observed in their safety profiles. Sensitivity analysis presented consistency in the overall estimates across these analyses. Consistent results were observed through frequentist and bayesian approaches with the same studies.
CONCLUSIONS AND RELEVANCE
Comprehensive analysis suggests that anti-PD-1 exhibited favorable survival outcomes and a safety profile comparable to that of anti-PD-L1, which may provide a useful guide for clinicians.
Topics: Antineoplastic Agents, Immunological; B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 31876895
DOI: 10.1001/jamaoncol.2019.5367 -
Blood Advances Jan 2023Relapsed/refractory primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) are associated with short survival and... (Meta-Analysis)
Meta-Analysis
Relapsed/refractory primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. Anti-CD19 chimeric antigen receptor (CAR) T cells, effective in systemic large B-cell lymphoma (LBCL), have shown responses in PCNSL and SCNSL in early reports, but with limited sample size. We, therefore, performed a comprehensive systematic review and meta-analysis of all published data describing CAR T-cell use in PCNSL and SCNSL. This identified 128 patients with PCNSL (30) and SCNSL (98). Our primary objectives were to evaluate CAR T-cell specific toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS] and cytokine release syndrome [CRS]) as well as response rates in these 2 populations. Seventy percent of patients with PCNSL had CRS of any grade (13% grade 3-4) and 53% had ICANS of any grade (18% grade 3-4). Comparatively, 72% of the SCNSL cohort experienced CRS of any grade (11% grade 3-4) and 48% had ICANS of any grade (26% grade 3-4). Of the patients with PCNSL, 56% achieved a complete remission (CR) with 37% remaining in remission at 6 months. Similarly, 47% of patients with SCNSL had a CR, with 37% in remission at 6 months. In a large meta-analysis of central nervous system (CNS) lymphomas, toxicity of anti-CD19-CAR T-cell therapy was similar to that of registrational studies in systemic LBCL with no increased signal of neurotoxicity observed. Encouraging efficacy was demonstrated in patients with CNS lymphoma with no discernible differences between PCNSL and SCNSL.
Topics: Humans; Antigens, CD19; Central Nervous System Neoplasms; Cytokine Release Syndrome; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms, Second Primary; Neurotoxicity Syndromes
PubMed: 36260735
DOI: 10.1182/bloodadvances.2022008525 -
Cells Aug 2023Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC.
METHODS
Prisma guidelines were followed for this systematic review and meta-analysis. Eligible studies were searched on PubMed. Studies published between 2017 and 2022, reporting data on PD-1/PD-L1 expression and other immune-related biomarkers in patients with BTC, were considered eligible.
RESULTS
A total of 61 eligible studies were identified. Despite the great heterogeneity between 39 studies reporting data on PD-L1 expression, we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs. The mean expression percentages of PD-L1 were 27.3%, 21.3%, and 27.4% in intrahepatic cholangiocarcinomas (iCCAs-15 studies), perihilar-distal CCAs (p/dCCAs-7 studies), and gallbladder cancer (GBC-5 studies), respectively. Furthermore, 4.6% (95% CI 2.38 to 6.97) and 2.5% (95% CI 1.75 to 3.34) of BTCs could be classified as TMB-H and MSI/MMRd tumors, respectively.
CONCLUSION
From our analysis, PD-L1 expression was found to occur approximately in 26% of BTC patients, with minimal differences based on anatomical location. TMB-H and MSI molecular phenotypes occurred less frequently. We still lack a reliable biomarker, especially in patients with mismatch-proficient tumors, and we must need to make an effort to conceive new prospective biomarker discovery studies.
Topics: Humans; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Biliary Tract Neoplasms; Immunotherapy; Biomarkers; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37626908
DOI: 10.3390/cells12162098