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Cytotherapy Sep 2022The existing evidence about the impact of bridging therapy (BT) on chimeric antigen receptor (CAR)-T cell therapy in patients with large B cell lymphoma (LBCL) is... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis of the association between bridging therapy and outcomes of chimeric antigen receptor T cell therapy in patients with large B cell lymphoma.
BACKGROUND
The existing evidence about the impact of bridging therapy (BT) on chimeric antigen receptor (CAR)-T cell therapy in patients with large B cell lymphoma (LBCL) is conflicting. Therefore, we reviewed all available evidence to examine the association between BT and CAR-T therapy outcomes by systematic review and meta-analysis approach.
METHODS
Two reviewers independently searched Embase, PubMed, Web of Science, and Cochrane library to identify all records that described BT for LBCL treated with CAR-T. We then applied a fixed- or random-effects meta-analysis to estimate the pooled hazard ratios (HRs) and rate ratio (RRs) for efficacy and safety endpoints and assessed differences across various BT modalities. The Newcastle-Ottawa Scale was used to evaluate study quality.
RESULTS
Twenty-six reports from 24 studies involving 2014 patients were included in the analysis. Pooled results showed that patients requiring BT had significantly worse 1-year overall survival rate (RR = 0.76, 95% confidence interval [CI] 0.68-0.85, P < 0.001), 1-year progression-free survival rate (RR = 0.71, 95% CI 0.60-0.85, P < 0.001), progression-free survival (HR = 1.35, 95% CI 1.07-1.69, P = 0.01), overall response rate (RR = 0.88, 95% CI 0.81-0.95, P = 0.001), complete response rate (RR = 0.78, 95% CI 0.65-0.93, P = 0.005), and grade ≥3 immune effector cell-associated neurotoxicity syndrome (RR = 1.43, 95% CI 1.10-1.87, P = 0.007), and tended to have poorer overall survival (HR = 1.42, 95% CI 0.99-2.02, P = 0.056) and grade ≥3 cytokine release syndrome (RR = 1.59, 95% CI 0.92-2.75, P = 0.096). Prolonged cytopenias were the common toxicity event associated with BT. Radiotherapy may serve as a promising BT option that can provide safe and effective disease control for patients with LBCL before CAR-T infusion. The inconsistency of patient baselines in the current study hindered further comparisons between different BT modalities. Most of the available evidence was rated as low quality because of concerns over low comparability.
CONCLUSION
BT appears to be associated with comparatively poor efficacy and safety outcomes after CAR-T infusion. However, due to the considerable heterogeneity between the BT and non-BT cohorts at disease baseline, no definitive conclusions can be made for the true impact of BT on CAR-T until further randomized studies are conducted.
Topics: Cell- and Tissue-Based Therapy; Cytokine Release Syndrome; Humans; Immunotherapy, Adoptive; Lymphoma, B-Cell; Progression-Free Survival; Receptors, Chimeric Antigen; Treatment Outcome
PubMed: 35568624
DOI: 10.1016/j.jcyt.2022.03.009 -
Journal For Immunotherapy of Cancer Apr 2023The number of clinical studies evaluating the benefit of cytokine-induced killer cell (CIK) therapy, an adoptive immunotherapy, for colorectal cancer (CRC) is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The number of clinical studies evaluating the benefit of cytokine-induced killer cell (CIK) therapy, an adoptive immunotherapy, for colorectal cancer (CRC) is increasing. In many of these trials, CIK therapy was coadministered with conventional cancer therapy. The aim of this review is to systematically assess the available literature, in which the majority were only in Chinese, on CIK therapy for the management of CRC using meta-analysis and to identify parameters associated with successful CIK therapy implementation.
METHODS
Prospective and retrospective clinical studies which compared CIK therapy to non-CIK therapy in patients with CRC were searched for electronically on MEDLINE, Embase, China National Knowledge Infrastructure, and Wanfang Data databases. The clinical endpoints of overall survival (OS), progression-free survival (PFS), OS and PFS rates, overall response rate (ORR), and toxicity were meta-analyzed using HR and relative ratio (RR), and subgroup analyses were performed using chi-square (χ) test and I-squared (I) statistics for study design, disease stage, cotherapy type, and timing of administration.
RESULTS
In total, 70 studies involving 6743 patients were analyzed. CIK therapy was favored over non-CIK therapy for OS (HR=0.59, 95% CI: 0.53 to 0.65), PFS (HR=0.55, 95% CI: 0.47 to 0.63), and ORR (RR=0.65, 95% CI: 0.57 to 0.74) without increasing toxicity (HR=0.59, 95% CI: 0.16 to 2.25). Subgroup analyses on OS and PFS by study design (randomized vs non-randomized study design), disease stage (Stage I-III vs Stage IV), cotreatment with dendritic cells (DCs) (CIK vs DC-CIK therapy), or timing of therapy administration (concurrent vs sequential with coadministered anticancer therapy) also showed that the clinical benefit of CIK therapy was robust in any subgroup analysis. Furthermore, cotreatment with DCs did not improve clinical outcomes over CIK therapy alone.
CONCLUSION
Compared with standard therapy, patients who received additional CIK cell therapy had favorable outcomes without increased toxicity, warranting further investigation into CIK therapy for the treatment of CRC.
Topics: Humans; Colorectal Neoplasms; Cytokine-Induced Killer Cells; Immunotherapy, Adoptive; Prospective Studies; Retrospective Studies; Clinical Trials as Topic
PubMed: 37117007
DOI: 10.1136/jitc-2023-006764 -
Applied Bionics and Biomechanics 2022To explore the differential efficacy of chemoradiotherapy combined with adoptive immunotherapy and radiochemotherapy alone in patients with non-small-cell lung cancer...
The Combined Clinical Efficacy and Safety Analysis of Adoptive Immunotherapy with Radiotherapy and Chemotherapy in Non-Small-Cell Lung Cancer: Systematic Review and Meta-Analysis.
OBJECTIVE
To explore the differential efficacy of chemoradiotherapy combined with adoptive immunotherapy and radiochemotherapy alone in patients with non-small-cell lung cancer (NSCLC).
METHODS
Qualified randomized controlled trial (randomized controlled trial, RCT), or nonrandomized concurrent controlled trial (NRCCT), published in various databases, including PubMed, EMBASE, Chinese journal full-text database, Medline, Cochrane database, and VIP Chinese database, and the Revman5. 0 software performed the data analysis.
RESULTS
We found the significantly different curative effect between the experimental and control groups (OR = 1.94, 95% CI (1.46, 2.58), < 0.001, = 0%, = 4.59), effect of adoptive immunotherapy on the progression of disease (OR = 1.80, 95% CI (1.38, 2.35), < 0.001, = 0%, = 4.33), adoptive immunotherapy on overall survival (OR = 2.19, 95% CI (1.60, 2.99), < 0.001, = 0%, = 4.91), and adverse effects of adoptive immunotherapy (OR = 1.76, 95% CI (1.25, 2.48), = 0.001, = 0%, = 3.26).
CONCLUSION
Adoptive immunotherapy combined with microradiotherapy can decrease the recurrence of NSCLC and improve patient survival, as well as early patients can be benefited more significantly from immunotherapy.
PubMed: 35706510
DOI: 10.1155/2022/2731744 -
The Oncologist Jun 2023T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma.
METHODS
We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). We conducted logistic regression analyses to identify potential predictive factors for tumor response.
RESULTS
From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38% (95% CI, 27%-50%). Median PFS was 2, 9 months (95% CI, 1.4-3.1). A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03). In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007).
CONCLUSION
TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported for TILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011).
Topics: Male; Humans; Melanoma; Skin Neoplasms; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Melanoma, Cutaneous Malignant
PubMed: 37036865
DOI: 10.1093/oncolo/oyad078 -
International Journal of Molecular... Nov 2021The unprecedented successes of immunotherapies (IOs) including immune checkpoint blockers (ICBs) and adoptive T-cell therapy (ACT) in patients with late-stage cancer...
The unprecedented successes of immunotherapies (IOs) including immune checkpoint blockers (ICBs) and adoptive T-cell therapy (ACT) in patients with late-stage cancer provide proof-of-principle evidence that harnessing the immune system, in particular T cells, can be an effective approach to eradicate cancer. This instills strong interests in understanding the immunomodulatory effects of radiotherapy (RT), an area that was actually investigated more than a century ago but had been largely ignored for many decades. With the "newly" discovered immunogenic responses from RT, numerous endeavors have been undertaken to combine RT with IOs, in order to bolster anti-tumor immunity. However, the underlying mechanisms are not well defined, which is a subject of much investigation. We therefore conducted a systematic literature search on the molecular underpinnings of RT-induced immunomodulation and IOs, which identified the IFN-JAK-STAT pathway as a major regulator. Our further analysis of relevant studies revealed that the signaling strength and duration of this pathway in response to RT and IOs may determine eventual immunological outcomes. We propose that strategic targeting of this axis can boost the immunostimulatory effects of RT and radiosensitizing effects of IOs, thereby promoting the efficacy of combination therapy of RT and IOs.
Topics: Combined Modality Therapy; Humans; Immunotherapy; Interferons; Janus Kinases; Neoplasms; Radiotherapy; STAT Transcription Factors; Signal Transduction; T-Lymphocytes
PubMed: 34830176
DOI: 10.3390/ijms222212295 -
Journal of Clinical Oncology : Official... Mar 2015Vitiligo-like depigmentation in patients with melanoma may be associated with more favorable clinical outcome. We conducted a systematic review of patients with stage... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Vitiligo-like depigmentation in patients with melanoma may be associated with more favorable clinical outcome. We conducted a systematic review of patients with stage III to IV melanoma treated with immunotherapy to determine the cumulative incidence of vitiligo-like depigmentation and the prognostic value of vitiligo development on survival.
METHODS
We systemically searched and selected all studies on melanoma immunotherapy that reported on autoimmune toxicity and/or vitiligo between 1995 and 2013. Methodologic quality of each study was appraised using adapted criteria for systematic reviews in prognostic studies. Random-effect models were used to calculate summary estimates of the cumulative incidence of vitiligo-like depigmentation across studies. The prognostic value of vitiligo-like depigmentation on survival outcome was assessed using random-effects Cox regression survival analyses.
RESULTS
One hundred thirty-seven studies were identified comprising 139 treatment arms (11 general immune stimulation, 84 vaccine, 28 antibody-based, and 16 adoptive transfer) including a total of 5,737 patients. The overall cumulative incidence of vitiligo was 3.4% (95% CI, 2.5% to 4.5%). In 27 studies reporting individual patient data, vitiligo development was significantly associated with both progression-free-survival (hazard ratio [HR], 0.51; 95% CI, 0.32 to 0.82; P < .005) and overall survival (HR, 0.25; 95% CI, 0.10 to 0.61; P < .003), indicating that these patients have two to four times less risk of disease progression and death, respectively, compared with patients without vitiligo development.
CONCLUSION
Although vitiligo occurs only in a low percentage of patients with melanoma treated with immunotherapy, our findings suggest clear survival benefit in these patients. Awareness of vitiligo induction in patients with melanoma is important as an indicator of robust antimelanoma immunity and associated improved survival.
Topics: Disease-Free Survival; Humans; Hypopigmentation; Immunotherapy; Incidence; Kaplan-Meier Estimate; Melanoma; Neoplasm Staging; Odds Ratio; Prognosis; Skin Neoplasms; Vitiligo; Melanoma, Cutaneous Malignant
PubMed: 25605840
DOI: 10.1200/JCO.2014.57.4756 -
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 -
Cureus Sep 2021Osteosarcoma (OS) is the most common primary bone cancer affecting children and young adults, most often occurring at the metaphysis of long bones. At present, treatment... (Review)
Review
Osteosarcoma (OS) is the most common primary bone cancer affecting children and young adults, most often occurring at the metaphysis of long bones. At present, treatment with combinations of surgery and chemotherapy for the localized OS has only brought minuscule improvements in prognosis. In comparison, the advanced, metastatic, or recurrent forms of OS are often non-responsive to chemotherapy, adding to the dire need to develop new and efficient therapies. The question of interest investigated in this systematic review is whether immunotherapy can play a meaningful role in improving the clinical outcomes of children with OS. This article aims to summarize the preclinical and clinical research conducted thus far on potential therapeutic avenues for pediatric OS using immunotherapy, including methods like checkpoint inhibition, adoptive cellular therapy with T-cells, chimeric antigen receptor T (CAR-T), and natural killer (NK) cells. It also highlights the influence of the innate and adaptive immune system on the tumor microenvironment, allowing for OS progression and metastasis. This systematic review contains 27 articles and analyses of multiple clinical trials employing immunotherapeutic drugs to 785 osteosarcoma participants and over 243 pediatric patients. The articles were obtained through PubMed, PubMed Central, and ClinicalTrials.gov and individually assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist and the Cochrane risk-of-bias tool. The reviews reveal that immunotherapy's most significant impact on pediatric OS includes combining immune checkpoint blockers with traditional chemotherapy and surgery. However, due to the bimodal distribution of this aggressive malignancy, these studies cannot precisely estimate the overall effect and any potential life-threatening adverse events following therapy in children. Further research is required to fully assess the impact of these immunotherapies, including more extensive multinational clinical trials to focus on the pediatric population.
PubMed: 34725602
DOI: 10.7759/cureus.18349 -
Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796 -
The Indian Journal of Medical Research May 2016The effectiveness of interleukin-2 (IL-2) and induced killer cells for non-small cell lung cancer (NSCLC) is controversial. This study evaluates the efficacy and safety... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & OBJECTIVES
The effectiveness of interleukin-2 (IL-2) and induced killer cells for non-small cell lung cancer (NSCLC) is controversial. This study evaluates the efficacy and safety of interleukin-2 and induced killer cells on NSCLC, so as to provide references for further clinical practice and research.
METHODS
Relevant randomized controlled trials (RCTs) were searched in Cochrane library (Issue 2, 2013), Web of Science (1980-March 2013), PubMed (1966-March 2013), China Knowledge Resource Integrated database (CNKI) (1994-March 2013), China Biology Medicine database (CBM) (1978-March 2013), VIP (1989-March 2013), and Wan Fang databases (1997-March 2013). There were no language restrictions. After independent quality assessment and data extraction by two authors, meta-analysis was conducted by RevMan 5.1 software.
RESULTS
Ten RCTs were included. Odds ratio (OR), 95% confidence intervals (CI), P value expressed as test group (interleukin-2 or induced killer cells combined chemotherapy) versus control group (chemotherapy alone), was 2.02 (1.24, 3.29; P=0.004) for disease control rate. Hazard ratios (HR) (95% CI; P value), expressed as test group (interleukin-2 or induced killer cells) versus control group, were 0.60 (0.46, 0.79; P=0.0003) for overall survival of postoperative treatment, and 0.77 (0.60, 0.99; P =0.04) for overall survival of combination with chemotherapy. Mean differences (MD) (95% CI; P value), expressed as test group (interleukin-2 or induced killer cells) versus control group (after treatment), were 11.32 (6.32, 16.33; P=0.00001) for NK cells, 11.79 (2.71, 20.86; P=0.01) for CD3+ cells, 14.63 (2.62, 26.64; P=0.02) for CD4+ cells, and -4.49 (-7.80, 1.18; P=0.008) for CD8+ cells.
INTERPRETATION & CONCLUSIONS
The meta-analysis showed that IL-2 or induced killer cells combination therapy was efficacious in treating NSCLC and improved overall survival. Further analysis of trials having adequate information and data need to be done to confirm these findings.
Topics: Carcinoma, Non-Small-Cell Lung; Cell- and Tissue-Based Therapy; Cytokine-Induced Killer Cells; Humans; Immunotherapy, Adoptive; Interleukin-2; Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 27748271
DOI: 10.4103/0971-5916.191738