Prognostic Effect of the Controlling Nutritional Status Score in Patients With Esophageal Cancer Treated With Immune Checkpoint Inhibitor
In recent years, a growing number of clinical studies have shown that immune checkpoint inhibitor (ICI) can increase the remission rate and improve the prognosis of patients with esophageal cancer. The Controlling Nutritional Status (CONUT) score is a novel nutritional indicator that can predict the prognosis of certain malignancies. We retrospectively analyzed the clinical data of 69 patients with advanced esophageal cancer treated with ICI and assessed the relationship between clinicopathological factors including CONUT score, systemic immune-inflammatory index (SII), and neutrophil-to-lymphocyte ratio and the prognosis....
Source: Journal of Immunotherapy - October 6, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

First-line Immune Checkpoint Inhibitor Versus Immune Checkpoint Inhibitor With Chemotherapy for Cisplatin-ineligible Metastatic Urothelial Carcinoma: Evidence From a Real-world, Multicenter Analysis
Immune checkpoint inhibitors (ICIs) are widely used for first-line cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC). However, whether to use ICIs as monotherapy or in combination with chemotherapy is still uncertain. We retrospectively analyzed cisplatin-ineligible patients with mUC who underwent first-line ICI monotherapy or ICI plus chemotherapy at 2 medical centers in Taiwan from 2016 to 2021. We calculated the objective response rate, progression-free survival, and overall survival (OS) using the Kaplan-Meier method and Cox regression model for multivariable analysis. In total, 130 patients were...
Source: Journal of Immunotherapy - October 6, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Humanized CD19-directed CAR-T Cell Therapy in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia With CNSL or Neurological Comorbidity
Chimeric antigen receptor T cell (CAR-T) therapy has breakthrough potential for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). However, because of the risk for neurotoxicity, trials usually exclude patients with central nervous system leukemia (CNSL) or active neurological comorbidities (NC). Here, we evaluated the efficacy and neurotoxicity of humanized CD19-directed CAR-T therapy for R/R ALL with CNSL or NC. Of 12 enrolled patients, 4 had CNSL with bone marrow (BM) or testicular recurrence, 3 had BM relapses with NC, and 5 had BM relapse without NC. Bridging chemotherapy was performed for high tumor burden...
Source: Journal of Immunotherapy - October 6, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

A Single Center Retrospective Study of the Impact of COVID-19 Infection on Immune-related Adverse Events in Cancer Patients Receiving Immune Checkpoint Inhibitors
Immune checkpoint inhibitors (ICIs) can cause a variety of immune-related adverse events (irAEs). The coronavirus disease 2019 (COVID-19) is associated with increased amounts of pro-inflammatory cytokines, which may affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Hence, in this study, we retrospectively analyzed ICI-treated adult patients with malignant solid tumors at a single institution between August 2020 and August 2021. Patients who had the most recent ICI treatment over 1-month before or after the positive COVID-19 test were excluded from the st...
Source: Journal of Immunotherapy - October 6, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

An Extended PD-L2 Cytoplasmic Domain Results From Alternative Splicing in NSCLC Cells
Antibody–based immunotherapy targeting the interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 has shown impressive clinical outcomes in various cancer types, including nonsmall cell lung cancer (NSCLC). However, regulatory mechanisms in this immune checkpoint pathway still needs clarification. PD-L2 is structurally homologous to PD-L1 and is a second PD-1 ligand. Alternative mRNA splicing from the CD274 and PDCD1LG2 genes holds the potential to generate PD-L1 and PD-L2 isoforms, respectively, with novel functionality in regulation of the PD-1 immune checkpoint pathway. Here, we describe alternative s...
Source: Journal of Immunotherapy - October 6, 2022 Category: Allergy & Immunology Tags: Basic Study Source Type: research

Immune Checkpoint Inhibitors Have Clinical Activity in Patients With Recurrent Chordoma
The aim of this study is to evaluate the outcomes and tolerance of immune checkpoint inhibitors (ICIs) for patients with recurrent chordoma. We reviewed the records of 17 patients with recurrent chordomas who received ICIs for progressing disease as part of their treatment between 2016 and 2020. Response was assessed using response evaluation criteria in solid tumors 1.1 criteria. The Kaplan-Meier method was used to estimate the duration of response, progression-free survival (PFS), and overall survival (OS). Clinical benefit was defined as having stable disease (SD), a partial response, or a complete response. The median ...
Source: Journal of Immunotherapy - September 10, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Nivolumab-associated Nasal Polyposis and Eosinophilic Asthma Responsive to Benralizumab, An Anti-IL5R Biologic
We present a case report of nivolumab-aggravated treatment-resistant chronic rhinosinusitis with nasal polyposis with asthma, suggestive of aspirin-exacerbated respiratory disease, normalized with the IL-5R antagonist benralizumab. For patients experiencing symptomatic complications of immunotherapy-associated eosinophilia, this case suggests anti-IL-5(R) biologics may durably resolve nasal polyposis and asthma symptoms, permitting continuity of checkpoint inhibitor therapy and sparing of systemic corticosteroids. Postulated mechanisms of checkpoint inhibition favoring eosinophilia and polyposis, and the uncertain effect o...
Source: Journal of Immunotherapy - September 10, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Clinical Characteristics and Outcomes of Gastritis Associated With Immune Checkpoint Inhibitors: Scoping Review
Among immune-related adverse events associated with immune checkpoint inhibitors, immune-mediated gastritis (IMG) has been rarely described in the literature and has not yet been well characterized. This scoping review aimed to characterize IMG in terms of precipitating agents, clinical presentations, and prognosis. After the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including “gastritis,” “immune checkpoint inhibitor,” and “immune-related adverse event” from their inception to De...
Source: Journal of Immunotherapy - September 10, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Serial Circulating Tumor DNA in Monitoring the Effect of Neoadjuvant and Adjuvant Immunotherapy in Patients With Colon Cancer: Case Series and Review of the Literature
This report summarizes clinical and molecular details for 3 patients with locally advanced or recurrent dMMR/MSI-H/polymerase epsilon (POLE) mutation-positive tumors treated with neoadjuvant/adjuvant immunotherapy. One stage IV recurrent colon cancer patient diagnosed with Lynch syndrome received adjuvant sintilimab monotherapy and had a progression-free survival (PFS) over 16 months, one stage Ⅲc colon cancer patient with MSI-H/high tumor mutation burden received neoadjuvant toripalimab monotherapy, was assessed as clinical complete response before surgery, continued with adjuvant sintilimab monotherapy and had a PFS ov...
Source: Journal of Immunotherapy - September 10, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Prognostic Potential of Metabolic Activity on 18F-FDG Accumulation in Advanced NSCLC Receiving Combining Chemotherapy Plus PD-1 Blockade
The objective response rate, median progression-free survival, and overall survival were 51.2%, 206 days, and 681 days, respectively. High SUVmax, TLG, and MTV significantly correlated with age and performance status (PS), C-reactive protein (CRP), and PS, CRP, albumin, and baseline tumor size, respectively. Univariate analysis identified albumin, TLG and MTV as significant predictors of progression-free survival, and CRP, albumin, TLG and MTV as significant factors for predicting overall survival. High TLG was confirmed as an independent factor associated with poor prognosis in multivariate analysis. In particular, TLG is...
Source: Journal of Immunotherapy - September 10, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

The Multi-Kinase Inhibitor Lucitanib Enhances the Antitumor Activity of Coinhibitory and Costimulatory Immune Pathway Modulators in Syngeneic Models
Lucitanib is a multi-tyrosine kinase inhibitor whose targets are associated with angiogenesis and other key cancer and immune pathways. Its antiangiogenic properties are understood, but lucitanib’s immunomodulatory activity is heretofore unknown. Lucitanib exhibited such activity in vivo, increasing CD3+, CD8+, and CD4+ T cells and decreasing dendritic cells and monocyte-derived suppressor cells in mouse spleens. Depletion of CD8+ T cells from syngeneic MC38 colon tumor-bearing mice reduced the antitumor efficacy of lucitanib and revealed a CD8+ T-cell-dependent component of lucitanib’s activity. The combination of luc...
Source: Journal of Immunotherapy - September 10, 2022 Category: Allergy & Immunology Tags: Basic Study Source Type: research

CTLA4, PD-1, PD-L1, PD-L2, TIM-3, TIGIT, and LAG3 DNA Methylation Is Associated With BAP1-Aberrancy, Transcriptional Activity, and Overall Survival in Uveal Melanoma
Uveal melanoma (UM) is an aggressive disease with poor response to oncological treatment, including immunotherapy. Loss of the epigenetic modifier BRCA1-associated protein 1 (BAP1) function drives UM oncogenesis and is associated with an immune-suppressive tumor microenvironment, poor prognosis, and a distinct DNA methylation and gene expression profile. Our study aimed to analyze comprehensively the DNA methylation status of the immune checkpoint genes PD-1, PD-L1, PD-L2, CTLA4, TIM-3 (HAVCR2), TIGIT, and LAG3 and its association with mRNA expression, BAP1-aberrancy, and patients’ survival. We analyzed the DNA methylati...
Source: Journal of Immunotherapy - August 15, 2022 Category: Allergy & Immunology Tags: Brief Communication Source Type: research

Pembrolizumab-Induced Acquired Amegakaryocytic Thrombocytopenia and Successful Combination Treatment With Eltrombopag, Romiplostim and Cyclosporine: A Brief Communication
Pembrolizumab is a humanized antibody directed against the programmed death-1 receptor on the cell surface, resulting in a T-cell-mediated immune response against tumor cells that can be complicated by immune-related adverse events. Here we present a novel case of pembrolizumab-induced acquired amegakaryocytic thrombocytopenia (AAT) in a patient with metastatic nasopharyngeal carcinoma. AAT is an incredibly rare and challenging entity for which there is no standardized treatment. We discuss our therapeutic approach using a calcineurin inhibitor and thrombopoietin receptor agonists for successful treatment of AAT and resump...
Source: Journal of Immunotherapy - August 15, 2022 Category: Allergy & Immunology Tags: Brief Communication Source Type: research

Lack of Efficacy of Immune Checkpoint Inhibitors in Cancer Patients Older Than 75?
This research was designed to compare the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients among different age groups. Electronic databases were searched to identify relevant trials. Randomized-controlled trials (RCTs) with ICIs and RCTs that conducted subgroup analysis of overall survival (OS) and/or progression-free survival (PFS) based on age were included. Summary hazard ratio (HR) and 95% confidence interval (CI) were available. Totally, 35,777 individuals from 59 RCTs were recruited. ICIs can ameliorate OS and PFS of cancer patients in groups of below 65 year and 65–75 years. Conversely, patients ...
Source: Journal of Immunotherapy - August 15, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research

Brief Communication on the Impact of β-blockers on Outcomes in Patients Receiving Cancer Immunotherapy
This study is a systematic review and meta-analysis of clinical studies. A comprehensive literature search was performed up to May 2022. Studies were included if they reported hazard ratios (HRs) of overall survival (OS), all-cause mortality or progression-free survival (PFS) associated with BBs in patients with solid organ cancer treated with immunotherapy. Study-specific HRs and 95% confidence intervals were pooled in random effects meta-analyses. Nine studies involving over 6350 patients with melanoma, lung, renal, urothelial, or other solid cancers treated with a range of immunotherapies met the inclusion criteria. Acr...
Source: Journal of Immunotherapy - August 15, 2022 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research