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Expert Review of Hematology 2024This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab.
METHODS
PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies.
RESULTS
The pooled complete remission (CR) rate and minimal residual disease (MRD) negative rate were 48%, 31% for blinatumomab, and 86% and 80% for CAR T-cell therapy.
CONCLUSIONS
The CAR T-cell therapy group exhibited a higher likelihood of CR rate than the blinatumomab group in every analysis regardless of adjustment subgroups. CAR T-cell therapy was associated with a significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with blinatumomab (2-year OS 55% vs 25%; 2-year RFS 40% vs 22%). CAR T-cell therapy was more effective for achieving CR and bridging to allogeneic hematopoietic stem cell transplantation (allo-SCT) than blinatumomab (2-year OS 75% vs. 57%). An emerging role for blinatumomab is as a bridging agent pre-SCT, and for patients who achieve an MRD-negative state pre-SCT, post-SCT outcomes are expected to be the same as CAR-T. For adverse effects (AEs), blinatumomab was associated with a lower rate of grade ≥3 hematological toxicity, CRS, and neurological events.
Topics: Humans; Immunotherapy, Adoptive; Hematopoietic Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antibodies, Bispecific; Recurrence; Antigens, CD19
PubMed: 38135295
DOI: 10.1080/17474086.2023.2298732 -
Journal For Immunotherapy of Cancer Oct 2022The addition of cetuximab significantly increased the antitumor effect of programmed cell death protein 1 (PD-1) inhibitors in recurrent or metastatic head and neck... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The addition of cetuximab significantly increased the antitumor effect of programmed cell death protein 1 (PD-1) inhibitors in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, preliminary analyses suggested that human papillomavirus (HPV)-positive disease benefited less than HPV-negative disease. Therefore, we conducted a meta-analysis to assess whether the efficacy of the combination therapy varied according to HPV status in HNSCC.
METHODS
We identified clinical trials of patients with recurrent or metastatic HNSCC who received PD-1 inhibitor monotherapy or the combination therapy of cetuximab plus a PD-1 inhibitor. The participants were divided into four groups based on the type of therapy (combination vs monotherapy) and HPV status (positive vs negative). We focused on three comparisons (monotherapy vs combination therapy by HPV status and HPV-positive vs HPV-negative disease in combination therapy). The primary and secondary endpoints were objective response rate (ORR) and 1-year overall survival (OS) rate, respectively. The ORR and 1-year OS rate were pooled using random-effects models for each group and were compared for the different comparisons.
RESULTS
Overall, 802 patients from seven trials were eligible for the ORR assessment; of which, 684 patients received PD-1 inhibitor monotherapy and 118 patients underwent the combination therapy. Compared with PD-1 inhibitor monotherapy, the addition of cetuximab improved the ORR in HPV-negative disease (pooled ORR in monotherapy vs combination therapy: 15% vs 46%, p<0.001) but not in HPV-positive disease (17% vs 18%, p=0.686). The efficacy of adding cetuximab was consistent for the 1-year OS rate in HPV-negative disease (pooled 1-year OS rate in monotherapy vs combination therapy: 36% vs 59%, p<0.001) and in HPV-positive disease (40% vs 55%, p=0.252). After the combination therapy, HPV-positive disease had a significantly lower ORR than HPV-negative disease (odds ratio: 0.29, p=0.004), but no differences were shown in the 1-year OS rate.
CONCLUSIONS
Our meta-analysis suggests that the addition of cetuximab to a PD-1 inhibitor is more effective compared with PD-1 inhibitor monotherapy only in patients with HPV-negative HNSCC. Despite the retrospective nature of this meta-analysis, these findings should help in designing relevant clinical trials rationally.
Topics: Cetuximab; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Papillomaviridae; Papillomavirus Infections; Programmed Cell Death 1 Receptor; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 36253001
DOI: 10.1136/jitc-2022-005158 -
Clinical Genitourinary Cancer Oct 2022Nivolumab, a PD-1 ICI has been recently approved for the adjuvant treatment of high-risk MIUC patients. However, conflicting data from another randomized controlled... (Meta-Analysis)
Meta-Analysis Review
A Systematic Review and Meta-Analysis of the Role of Immune Checkpoint Inhibitors (ICI) as Adjuvant Treatment for Localized High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC).
Nivolumab, a PD-1 ICI has been recently approved for the adjuvant treatment of high-risk MIUC patients. However, conflicting data from another randomized controlled trial (RCT) with atezolizumab makes the benefit of this treatment uncertain. We performed a systematic review and study-level meta-analysis to evaluate the benefit in terms of disease-free survival (DFS) with ICI adjuvant treatment for patients with high-risk MIUC. Considering the Preferred Reporting Items for Systematic Review statement, a systematic search was performed in PUBMED/MEDLINE, Scopus and EMBASE up to October 30, 2021. The statistical analysis was performed by RevMan 5.4 software in intention-to-treat (ITT) population and in predetermined subgroups. Two RCTRCT, with a total of 1518 patients, met the inclusion criteria. Systemic immunotherapy was atezolizumab for 406 patients and nivolumab for 353 patients. In the ITT population there was a nonsignificant benefit with the systemic adjuvant immunotherapy (HR:0.79, 95% CI 0.62-1.00; z = 2.00) but with high heterogeneity (I = 65%). Regarding the subgroups, there was no benefit in PD-L1 negative (HR:0.81, 95% CI 0.70-1.00; z = 1.96, I = 0%) and in non-neoadjuvant chemotherapy (HR:0.95, 95% CI 0.78-1.15; z = 0.56, I = 0%). Adjuvant treatment with ICI to patients with high-risk MIUC reveals a nonsignificant impact in DFS. The lack of clinical benefit was demonstrated in all subgroups. These data reinforce the need for a careful selection of patients before offering this approach in daily practice.
Topics: B7-H1 Antigen; Carcinoma, Transitional Cell; Humans; Immune Checkpoint Inhibitors; Muscles; Nivolumab; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 35595632
DOI: 10.1016/j.clgc.2022.04.008 -
BMC Cancer May 2023Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, worldwide. The predominant causative factor for HCC is hepatitis B virus (HBV)... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the unresectable hepatocellular carcinoma and the benefit for hepatitis B virus etiology subgroup: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, worldwide. The predominant causative factor for HCC is hepatitis B virus (HBV) infection. We conducted a meta-analysis to estimate the efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the first-line treatment of the unresectable HCC and to evaluate the benefits of different geographic regions and etiology stratifications.
METHODS
Randomized clinical trials published up to 12th November 2022 were searched by online databases. Moreover, effects of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were extracted from included studies. Pooled odds ratio (OR) and 95% CI for objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) were calculated.
RESULTS
A total of 3057 patients from five phase III randomized clinical trials were collected and reviewed for this meta-analysis. The pooled HR of OS (HR = 0.71; 95% CI: 0.60-0.85) and PFS (HR = 0.64; 95% CI: 0.53-0.77) demonstrated significantly better benefit in PD-1/PD-L1 inhibitors combination group than targeted monotherapy to treat unresectable HCC. In addition, combination therapy showed better ORR and DCR, with ORs of 3.29 (95% CI: 1.92-5.62) and 1.88 (95% CI: 1.35-2.61), respectively. The subgroup analysis indicated that PD-1/PD-L1 inhibitors combination therapy was significantly superior to anti-angiogenic monotherapy for HBV-related HCC in terms of OS (HR = 0.64; 95% CI: 0.55-0.74) and PFS (HR = 0.53; 95% CI:0.47-0.59), while there was no significant difference in patients with HCV (OS, HR = 0.81, p = 0.1) or non-viral (OS, HR = 0.91, p = 0.37; PFS, HR = 0.77, p = 0.05).
CONCLUSIONS
Meta-analysis revealed for the first-time that PD-1/PD-L1 inhibitors combination therapy for unresectable HCC was associated with better clinical outcomes than anti-angiogenic monotherapy, especially for HBV infection and Asian population.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B; Hepatitis B virus; Immune Checkpoint Inhibitors; Liver Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 37226111
DOI: 10.1186/s12885-023-10960-w -
Frontiers in Immunology 2021IKAROS and CTLA4 deficiencies are inborn errors of immunity and show similar clinical phenotypes, including hypogammaglobulinemia and autoimmune diseases (ADs). However,...
IKAROS and CTLA4 deficiencies are inborn errors of immunity and show similar clinical phenotypes, including hypogammaglobulinemia and autoimmune diseases (ADs). However, the differences in clinical features and pathogenesis of these are not fully understood. Therefore, we performed systematic literature reviews for IKAROS and CTLA4 deficiencies. The reviews suggested that patients with IKAROS deficiency develop AD earlier than hypogammaglobulinemia. However, no study assessed the detailed changes in clinical manifestations over time; this was likely due to the cross-sectional nature of the studies. Therefore, we conducted a retrospective longitudinal study on IKAROS and CTLA4 deficiencies in our cohort to evaluate the clinical course over time. In patients with IKAROS deficiency, AD and hypogammaglobulinemia often develop in that order, and AD often resolves before the onset of hypogammaglobulinemia; these observations were not found in patients with CTLA4 deficiency. Understanding this difference in the clinical course helps in the clinical management of both. Furthermore, our results suggest B- and T-cell-mediated ADs in patients with IKAROS and CTLA4 deficiencies, respectively.
Topics: Autoimmune Diseases; CTLA-4 Antigen; Humans; Ikaros Transcription Factor; Longitudinal Studies; Metabolism, Inborn Errors; Primary Immunodeficiency Diseases; Retrospective Studies
PubMed: 35087518
DOI: 10.3389/fimmu.2021.784901 -
Journal of Immunotherapy (Hagerstown,... Sep 2023Programmed death 1 (PD-1) inhibitors have emerged as the new standard of care for the second-line treatment of advanced esophageal squamous cell carcinoma. There have... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety Profile of PD-1 Inhibitors Versus Chemotherapy in the Second-Line Treatment of Advanced Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Programmed death 1 (PD-1) inhibitors have emerged as the new standard of care for the second-line treatment of advanced esophageal squamous cell carcinoma. There have been lots of research lately concerning the topic. A comprehensive assessment of the efficacy and safety profile between PD-1 inhibitors and chemotherapy is warranted. Hence, we carried out a systematic review and meta-analysis to illustrate this issue. Pubmed, Embase, Cochrane Library, and Embase were searched systematically until May 1, 2022. We extracted data on efficacy and safety and calculated the pooled hazard ratios (HRs) and relative ratios (RRs) with 95% CI using randomized-effect or fixed-effect models. A subgroup analysis was applied to explore the factors modifying the response to PD-1 inhibitors. Ultimately, a total of 5 studies involving 1970 patients were included in our meta-analysis. PD-1 inhibitors group could attain greater overall survival (OS) benefit (HR = 0.73, 95% CI: 0.66-0.81, P < 0.001) and nearly favorable progression-free survival (HR = 0.89, 0.76-1.04, P = 0.13). Treatment-related adverse events (RR = 0.76, 95% CI: 0.64-0.91, P = 0.004) and level 3-5 treatment-related adverse events (RR = 0.40, 95% CI: 0.32-0.49, P < 0.001) were significantly diminished in PD-1 inhibitors groups. Among all modifying factors, programmed death ligand 1 combined positive score was positively associated with the patient's OS. The analysis suggests that PD-1 inhibitors exhibited better survival outcomes and safety profiles than standard-of-care chemotherapy. High levels of programmed death ligand 1 combined positive scores were associated with an enhanced response to PD-1 immunotherapies concerning OS.
Topics: Humans; Immune Checkpoint Inhibitors; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic; B7-H1 Antigen; Lung Neoplasms
PubMed: 37338278
DOI: 10.1097/CJI.0000000000000479 -
Expert Review of Anticancer Therapy 2023Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of all studied ICIs.
METHODS
We conducted a comprehensive search to identify the relevant publications (PROSPERO registration ID: CRD42023470649). Then we performed a meta-analysis to evaluate the efficacy of different ICIs for metastatic melanoma. We used Cochrane's tool to assess the quality of studies. The outcome measures were overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS).
RESULTS
Twenty reports of RCTs entered our systematic review, 18 of which were included in our data analysis. ICIs showed improved survival compared with control group (hazard ratio (HR) = 0.57; 95% CI: 0.43-0.71; <0.001). Using a meta-regression, we found a significant relation between patients' mean age and their OS (<0.001, = 100.00%). Also, our analysis revealed greater HR for CTLA-4 inhibitors than PD-1/PD-L1 inhibitors (HR = 0.71, 95%CI: 0.63-0.79, <0.001 vs. HR = 0.63, 95%CI: 0.46-0.79, <0.001). The effect sizes of different types of PD-1/PD-L1 inhibitors were comparable.
CONCLUSION
Our results suggest that ICI-based immunotherapy is associated with enhanced OS, PFS, and RFS ( < 0.001) and will assist clinicians in choosing the optimal approach toward treating metastatic melanoma.
Topics: Humans; Melanoma; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Skin Neoplasms; CTLA-4 Antigen
PubMed: 37908134
DOI: 10.1080/14737140.2023.2278509 -
Critical Reviews in Oncology/hematology Apr 2022Advanced stage malignant mesothelioma (asMM) patients have poor prognosis. Several trials investigated the role of programmed cell death protein-1 (PD-1) and its ligand... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Advanced stage malignant mesothelioma (asMM) patients have poor prognosis. Several trials investigated the role of programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) in pre-treated asMM.
METHODS
A systematic review of the literature of clinical trials testing single-agent anti PD-1/PD-L1 ICIs in pre-treated asMM was performed. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) data were extracted. The predictive role of PD-L1 was assessed.
RESULTS
We selected 13 studies including 888 patients. ORR and DCR were 18.1% (95% confidence interval [CI] 13.9-22.8%) and 55.4% (95% CI: 48.1-62.5%), respectively. Median PFS and OS ranged from 2.1 to 5.9 and from 6.7 to 20.9 months, respectively. ORR according to PD-L1 was 27.0% (95% CI: 18.7-36.2%).
CONCLUSIONS
Anti-PD-(L)1 ICIs might be considered a treatment option for chemotherapy-resistant asMM, even if reliable predictive factors are still lacking.
Topics: B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Mesothelioma, Malignant; Programmed Cell Death 1 Receptor; Progression-Free Survival
PubMed: 35192932
DOI: 10.1016/j.critrevonc.2022.103639 -
Clinical Transplantation Aug 2021Although HLA matching is considered as a key genetic predictor of allo-HSCT outcomes, genetic polymorphisms in non-HLA genes, especially in genes encoding... (Meta-Analysis)
Meta-Analysis Review
Genetic Polymorphisms of Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and clinical outcomes post-allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis.
BACKGROUND AND OBJECTIVE
Although HLA matching is considered as a key genetic predictor of allo-HSCT outcomes, genetic polymorphisms in non-HLA genes, especially in genes encoding immunoregulatory proteins, have also been proposed as additional risk factors linked to the occurrence of transplant complications. This study aimed to carry out a systematic review and meta-analysis from all eligible cohort studies to determine the effect of CTLA-4 gene polymorphisms, including rs231775, rs3087243, rs4553808, rs5742909, and rs733618, on clinical outcomes in patients receiving an allo-HSCT.
METHODS
A systematic literature search in PubMed, Web of Science, and Scopus was performed to identify the relevant studies, and related information was extracted. The effect size (ES) and corresponding 95% confidence intervals (CIs) were calculated to estimate the association.
RESULTS
16 studies were eligible and included in the meta-analysis. The pooled results showed that only the dominant models of rs3087243 were significantly associated with chronic GVHD (cGVHD), while other SNPs were not significantly associated with overall survival, disease-free survival, relapse, and GVHD.
CONCLUSIONS
Our study represents, for the first time, a comprehensive meta-analysis on the role of CTLA-4 polymorphisms on outcomes after allo-HSCT. The results indicate that the CT60 CTLA-4 polymorphism could be a significant risk factor for cGVHD.
Topics: CTLA-4 Antigen; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 34008865
DOI: 10.1111/ctr.14364 -
Frontiers in Immunology 2022An influx of systematic reviews (SRs) of programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) checkpoint inhibitors in cancer treatment with or without... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An influx of systematic reviews (SRs) of programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) checkpoint inhibitors in cancer treatment with or without meta-analysis and with different methodological quality and inconsistent results have been published, confusing clinical decision making. The aim of this study was to comprehensively evaluate and summarize the current evidence of PD-(L)1 inhibitors in the treatment of cancer.
METHODS
A comprehensive search of SRs, which included meta-analyses of PD-(L)1 inhibitors on cancer, was performed on eight databases with a cutoff date of 1 January 2022. Two authors independently identified SRs, extracted data, assessed the report quality according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, evaluated the methodological quality by the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and appraised the quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).
RESULTS
A total of 172 SRs with meta-analysis met the inclusion criteria. The report quality of included SRs was quite good, with 128 (74.42%) SRs of high quality and 44 (25.58%) of moderate quality. The methodological quality was alarming, as only one (0.58%) SR had high quality, five (2.91%) SRs had low quality, and the other 166 (96.51%) SRs had critically low quality. For GRADE, 38 (3.77%) outcomes had high-quality evidence, 288 (28.57%) moderate, 545 (54.07%) low, and 137 (13.59%) critically low-quality evidence. Current evidence indicated that treatment with PD-(L)1 inhibitors were significantly effective in non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, malignant melanoma, renal cell carcinoma, and urothelial carcinoma, breast cancer, and head and neck squamous cell carcinoma with PD-L1 expression level≥1%, whereas the evidence in gastroesophageal and colorectal tumors is still controversial. Monotherapy with PD-(L)1 inhibitors was associated with a lower frequency of any grade and high-grade adverse events (AEs). The incidence of any grade and high-grade AEs caused by PD-(L)1 inhibitors in combination with other therapies was no lower than the controls. However, PD-(L)1 inhibitors were associated with a higher frequency of any grade and high-grade immune-related AEs.
CONCLUSIONS
PD-(L)1 inhibitors appeared to be effective and safe for cancer treatment, except for gastrointestinal tumors; however, the quality of the evidence is not convincing. Future studies should improve methodological quality and focus on the sequential trial analysis of subgroups and safety.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/prospero, identifier CRD42020194260.
Topics: Apoptosis; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Programmed Cell Death 1 Receptor; Urinary Bladder Neoplasms
PubMed: 35911744
DOI: 10.3389/fimmu.2022.953761