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Journal of Thoracic Oncology : Official... Jan 2024Dual immune checkpoint blockers regimen represents a standard first-line therapy in unresectable pleural mesothelioma (PM). Novel combination strategies, including... (Meta-Analysis)
Meta-Analysis
Meta-Analysis on the Combination of Chemotherapy With Programmed Death-Ligand 1 and Programmed Cell Death Protein 1 Blockade as First-Line Treatment for Unresectable Pleural Mesothelioma.
INTRODUCTION
Dual immune checkpoint blockers regimen represents a standard first-line therapy in unresectable pleural mesothelioma (PM). Novel combination strategies, including immune checkpoint blockers and antiangiogenic drugs, are currently under investigation in this setting. We aimed to assess the efficacy of the chemoimmunotherapy combination by reference to literature evidence.
METHODS
A systematic review and meta-analysis of trials with first-line platinum-based chemotherapy associated with programmed death-ligand 1 and programmed cell death protein 1 agent in unresectable PM. We estimated the weighted summary proportion of disease response, along with the landmark probability of survival outcomes.
RESULTS
A total of 349 patients with unresectable PM from four trials (DREAM, PrE0505, JME-001, and IND.227) were included, 79% (n = 274) with epithelioid and 21% (n = 75) with nonepithelioid histologic type. In aggregate, the objective response rate was 59.2% (95% confidence interval [CI]: 50.3%-67.9%) and disease control rate was 92.2% (95% CI: 89.2%-94.8%). Comparing epithelioid versus nonepithelioid tumors, the objective response rate was 64.5% versus 46.4%, (p < 0.001) and the disease control rate was 92.3% versus 80.0%, (p = 0.043), with an OR of 2.56 (95% CI: 1.51-4.32) for disease response and of 3.37 (95% CI: 0.99-11.47) for disease control. The aggregated estimated probability of progression-free survival was 63% (95% CI: 53%-71%) at 6 months and 25% (95% CI: 21%-31%) at 12 months, whereas the 6-, 12- and 24-month overall survival rates were 88% (95% CI: 81%-93%), 71% (95% CI: 61%-79%) and 39% (95% CI: 34%-45%), respectively.
CONCLUSIONS
According to our analysis, first-line chemoimmunotherapy holds promise as a new treatment approach for PM, exhibiting encouraging survival outcomes and an enhanced response rate, including for the epithelioid subtype. Ongoing studies are necessary to establish its precise placement within the treatment algorithm.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Immune Checkpoint Inhibitors; Ligands; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 37567387
DOI: 10.1016/j.jtho.2023.08.004 -
Leukemia & Lymphoma 2023Relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) is a challenging disease with low rates of remission and survival in adult patients. Anti-CD19... (Meta-Analysis)
Meta-Analysis
Differences in efficacy and safety among CAR-Ts anti-CD19/CD22, anti-CD19, and anti-CD22, in adult patients with relapse/refractory B-cell acute lymphoblastic leukemia: a meta-analysis and systematic review.
Relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) is a challenging disease with low rates of remission and survival in adult patients. Anti-CD19 Chimeric Antigen Receptor T-cells (CAR-Ts) therapies have been approved for these patients. Dual-target CAR-Ts against CD19 and CD22 have recently been developed to improve the efficacy of the single-target therapy; however, extent of the improvement using this dual-target therapy has yet to be determined. We performed a meta-analysis of the outcome and safety of CAR-Ts, comparing anti-CD19 vs anti-CD22 vs dual-target anti-CD19/CD22 CAR-Ts, to elucidate the differences and limitations of these therapies in adult patients with R/R B-ALL. our results suggest that anti-CD19/CD22 CAR-Ts generate lower incidence of relapse and neurotoxicity, but similar results were obtained regarding complete remission, minimal residual disease, overall survival, and cytokine release syndrome compared with single-target anti-CD19 and anti-CD22 CAR-Ts.
Topics: Humans; Adult; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Lymphoma, B-Cell; Antigens, CD19; Acute Disease; Sialic Acid Binding Ig-like Lectin 2
PubMed: 37548560
DOI: 10.1080/10428194.2023.2243357 -
Frontiers in Immunology 2023The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Network Meta-Analysis; Neoplasms; Paclitaxel; Hypothyroidism; Pneumonia
PubMed: 37520574
DOI: 10.3389/fimmu.2023.1175809 -
International Journal of Molecular... Jul 2023In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options... (Review)
Review
In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies. While the mechanism of action of ICIs seems promising, the lack of a robust response limits their widespread use. Although the expression levels of programmed death ligand 1 (PD-L1) on tumor cells are used to predict ICI response, identifying new biomarkers, particularly those associated with the tumor microenvironment (TME), is crucial to address this unmet need. Recently, inflammatory cytokines such as interleukin-1 beta (IL-1β) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1β inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations. Recent advancements in our understanding of the intricate relationship between inflammation and oncogenesis, particularly involving the IL-1β/PD-1/PD-L1 pathway, have shed light on their application in lung cancer development and clinical outcomes of patients. Targeting these pathways in cancers like NSCLC holds immense potential to revolutionize cancer treatment, particularly for patients lacking targetable genetic mutations. However, despite these promising prospects, there remain certain aspects of this pathway that require further investigation, particularly regarding treatment resistance. Therefore, the objective of this review is to delve into the role of IL-1β in NSCLC, its participation in inflammatory pathways, and its intricate crosstalk with the PD-1/PD-L1 pathway. Additionally, we aim to explore the potential of IL-1β as a therapeutic target for NSCLC treatment.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immunotherapy; Lung Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Interleukin-1beta
PubMed: 37511306
DOI: 10.3390/ijms241411547 -
Critical Reviews in Oncology/hematology Sep 2023
Meta-Analysis
Comment on "A systematic review and meta-analysis of PD-1/PD-L1 inhibitors in specific patient subgroups with advanced gastro-oesophageal junction and gastric adenocarcinoma".
Topics: Humans; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Stomach Neoplasms; Adenocarcinoma
PubMed: 37487968
DOI: 10.1016/j.critrevonc.2023.104069 -
Oral Oncology Oct 2023HNSCC is one of the most common types of cancer worldwide and immune checkpoint inhibitor has shown favorable therapeutic effect in R/M HNSC. However, the application of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HNSCC is one of the most common types of cancer worldwide and immune checkpoint inhibitor has shown favorable therapeutic effect in R/M HNSC. However, the application of immunotherapy in untreated HNSCC still needs to be discovered since most R/M HNSCC patients have been treated before and their drug susceptibility and immune tumor microenvironment have changed. This meta-analysis tries to compare immunotherapy and immunochemotherapy in untreated HNSCC and give a reference for clinic application.
METHODS
Electronic databases, including PubMed, Embase, and Web of Science, were systematically searched from inception through August 31, 2022. The primary outcomes were efficacy, evaluated by objective response rate, 1-year OS and 1-year PFS, and safety, evaluated by grade 3-4 adverse reaction rate.
RESULTS
A total of 1092 patients from twenty-four studies were included, 282 (25.8%) of which had ORR reported. The average ORR was 37% (95%CI = 26%-49%). Immunochemotherapy could have higher ORR than immunotherapy patients (ORR: 61% vs 22%), and favorable 1-year overall survival from PD-L1 inhibitor (OS = 84%, 95%CI 76%-93%). Radiotherapy after neoadjuvant immunotherapy was equal with the other treatments like chemotherapy and surgery (84% vs 88%, subgroup df p = 0.7). There was no apparent difference between immunotherapy and immunochemotherapy (32% vs 42%, subgroup df p = 0.60).
CONCLUSION
HNSCC patients could benefit more from neoadjuvant immunochemotherapy.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Neoadjuvant Therapy; Immunotherapy; Head and Neck Neoplasms; B7-H1 Antigen; Lung Neoplasms; Tumor Microenvironment
PubMed: 37478574
DOI: 10.1016/j.oraloncology.2023.106479 -
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 -
Expert Review of Anticancer Therapy 2023Which patients may benefit more from immune checkpoint inhibitors (ICIs) is still an important question. The present study aimed to investigate the role of the PD-L1... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Which patients may benefit more from immune checkpoint inhibitors (ICIs) is still an important question. The present study aimed to investigate the role of the PD-L1 molecule in predicting the effectiveness of PD-1/PD-L1 inhibitors in gastric cancer patients.
METHOD
We searched PubMed, Scopus, Web of Science, and EMBASE databases as of 25 March 202225 March 2022.
RESULTS
Ten articles were included. When we used the TPS method for PD-L1 expression, none of the patients in tumor proportion score (TPS)≥1% and TPS < 1% groups took advantage of ICI therapy in terms of OS and PFS. However, gastric cancer patients with combined-positive score (CPS)≥1, CPS ≥ 5, and CPS ≥ 10 tumors represented superior OS for ICIs over the control agents, while their counterparts (i.e. patients with CPS < 1, CPS < 5, and CPS < 10 tumors) did not. In the subgroup analysis when patients with CPS ≥ 1 were selected, Nivolumab improved the OS and PFS remarkably by 26% and 25% when compared with control agents, respectively. However, Pembrolizumab significantly increased the rate of disease progression by 47% relative to the control medications.
CONCLUSION
Among patients suffering from gastric cancer, considering PD-L1 CPS thresholds seems to be a more reliable predictive factor than TPS threshold for lower rate of mortality when PD-1/PD-L1 inhibitors are administered.
Topics: Humans; Stomach Neoplasms; Immune Checkpoint Inhibitors; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Nivolumab
PubMed: 37466449
DOI: 10.1080/14737140.2023.2238896 -
Frontiers in Immunology 2023PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized controlled trials in accordance with the study and carried out meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors in mTNBC.
AIM
To systematically evaluate the efficacy and safety of PD-1/PD-L1 ICIs (hereinafter referred to as ICIs) in the treatment of mTNBC.
METHODS
As of 2023.2.5, Medline, PubMed, Embase, Cochrane library database and Web of Science were searched to determine the study in accordance with the trial of ICIs in the treatment of mTNBC. The assessment endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Meta-analysis of the included studies was performed using Revman 5.4.
RESULTS
A total of six trials with 3172 patients were included in this meta-analysis. The ORR of ICIs combined with chemotherapy was significantly improved compared with chemotherapy (HR=0.88, 95%CI: 0.81-0.94, I= 0%). For PFS, the experimental group were better than the control group in both intention-to-treat (ITT) population and PD-L1 positive population, showing statistical significance (ITT: HR=0.81, 95%CI: 0.74-0.89, P<0.05, I= 0%; PD-L1 positive: HR=0.72, 95%CI: 0.63-0.82, P<0.05, I= 18%); For OS, in the ITT population, no statistical difference was observed in either ICIs combined with chemotherapy(HR=0.92, 95%CI: 0.83-1.02, P=0.10)or immune monotherapy(HR=0.78, 95%CI: 0.44-1.36, P=0.37), in the PD-L1 positive population, ICIs group had better OS than chemotherapy group (HR=0.83, 95%CI: 0.74-0.93, P < 0.05); In safety, serious adverse event (SAE) was no statistically significant difference between the ICIs group and the chemotherapy group; however, the incidence of immune-related adverse event (irAE) was significantly higher in the ICIs group than in the chemotherapy group (HR=2.15, 95%CI: 1.45-3.19, P < 0.05).
CONCLUSION
ICIs combined with chemotherapy significantly improved the PFS of mTNBC, however, ICIs only improved the OS in PD-L1 positive people, and no statistical difference was observed in ITT population; while benefiting from ICIs, we found that irAE in ICIs group increased significantly, and its high rate of adverse events still needs to be taken seriously.
Topics: Humans; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Triple Negative Breast Neoplasms; B7-H1 Antigen; Control Groups
PubMed: 37377959
DOI: 10.3389/fimmu.2023.1206689 -
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