Bilateral Vocal Cord Paralysis Due to an Immune-related Adverse Event of Nivolumab: A Case Report
Summary:
Nivolumab is an anti-programmed death-1 inhibitor used in the treatment of cancer. Nivolumab has recently been approved as an adjuvant treatment for patients with stage IIIB, IIIC, and completely resected stage IV melanoma in the Netherlands. Despite the promising results of nivolumab, there is a wide variation in toxic side effects. A nivolumab-induced bilateral vocal cord paralysis (BVCP) was not reported. In this case, we present a nivolumab-induced BVCP. A 75-year-old man received nivolumab as adjuvant therapy for stage III melanoma. After the first cycle of nivolumab, this patient developed immune-related h...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Combination Therapy of Ipilimumab and Nivolumab-associated Toxic Epidermal Necrolysis (TEN) in a Patient With Metastatic Melanoma: A Case Report and Literature Review
Ipilimumab and nivolumab are immune checkpoint inhibitors used in the treatment of metastatic melanoma. The authors report the case of a 62-year-old white male individual with metastatic choroidal melanoma who had commenced adjuvant systemic treatment with combination checkpoint inhibitor therapy of intravenous ipilimumab (anti-cytotoxic T-lymphocyte antigen-4) and nivolumab (anti-programmed cell death-1) at 3-week cycle intervals. On day 4 after the second cycle, he developed an acute widespread rash. On examination there was confluent erythema with bullae and epidermal loss over 60% of the body surface area, with severe ...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Generation of Antitumor T Cells For Adoptive Cell Therapy With Artificial Antigen Presenting Cells
Adoptive cell therapy with ex vivo expanded tumor infiltrating lymphocytes or gene engineering T cells expressing chimeric antigen receptors (CAR) is a promising treatment for cancer patients. This production utilizes T-cell activation and transduction with activation beads and RetroNectin, respectively. However, the high cost of production is an obstacle for the broad clinical application of novel immunotherapeutic cell products. To facilitate production we refined our approach by using artificial antigen presenting cells (aAPCs) with receptors that ligate CD3, CD28, and the CD137 ligand (CD137L or 41BBL), as well as expr...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Basic Study Source Type: research
Sarcoid-like Reaction Discovered on EBUS-TBNA of Intrathoracic Lymph Nodes During Immunotherapy for Metastatic Melanoma
The use of immune checkpoint inhibitors has dramatically improved outcomes for patients with advanced melanoma and other malignancies. Checkpoint inhibitors are associated with a unique set of toxicities collectively known as immune-related adverse events, the incidence of which is rising in parallel with their increasing use in clinical practice. Immune-related adverse events are widely variable in their presentation and can affect virtually any organ system in the body. Sarcoid-like reactions in patients being treated with immune checkpoint inhibitors are rare and are typically multisystemic in nature with isolated pulmo...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Immune-related Neutropenia Following Treatment With Immune Checkpoint Inhibitors
The existing data with regard to immune-related neutropenia (irN), a rare (incidence—1%) immune-related adverse event of immune checkpoint inhibitors, are scarce. Eight patients with irN were identified through internal databases of 3 participating Israeli cancer centers. In addition, 11 original articles focusing on the clinical course of 24 patients with irN were selected during the PubMed search. Descriptive analysis of clinical and pathologic factors related to irN was performed (n=32); the effect of these on the irN outcomes was assessed. An algorithm for irN evaluation and treatment was proposed. The median time-to...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Blood Immune Cell Biomarkers in Patient With Lung Cancer Undergoing Treatment With Checkpoint Blockade
Characterization of host immune cell parameters before and during immunotherapy is expected to identify predictive biomarkers for clinical outcome. We prospectively monitored blood immune cells from 35 patients with advanced non–small cell lung cancer undergoing checkpoint inhibitor monotherapy. The aim was to identify parameters correlating with better/worse outcome. Peripheral blood was serially collected before each infusion at the onset and at cycle 3 and 5 of immunotherapy. A complete leukocyte blood count, the lymphocytic subpopulations and the percentages of both HLA-DRlow monocytes and dendritic cells (DC) were m...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Applicability of Routine Targeted Next-generation Sequencing to Estimate Tumor Mutational Burden (TMB) in Patients Treated With Immune Checkpoint Inhibitor Therapy
It remains unclear whether targeted next-generation sequencing (tNGS) conveys a reliable estimate of tumor mutational burden (TMB). We sequenced 79 archival samples of immune checkpoint inhibitors (ICPIs) recipients (57% lung cancer, 43% melanoma) using Ion Ampliseq Cancer Hotspot Panel. Employing multiple cutoff values, we verified that TMB by tNGS did not correlate with response or survival following ICPI. We found enrichment of ATM mutations in ICPI-refractory tumors (P=0.01) to correlate with worse survival (4.2 vs. 10 mo, P=0.03). Limited-coverage tNGS delivers an imprecise estimate of patients’ TMB but may aid id...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
An IgG1 Version of the Anti-transferrin Receptor 1 Antibody ch128.1 Shows Significant Antitumor Activity Against Different Xenograft Models of Multiple Myeloma: A Brief Communication
The transferrin receptor 1 (TfR1) is a meaningful target for antibody-based cancer therapy given its overexpression on malignant cells and its central role in cancer pathology. We previously developed a mouse/human chimeric IgG3 targeting human TfR1 (ch128.1), which exhibits significant antitumor activity against multiple myeloma (MM) in xenograft models of SCID-Beige mice bearing disseminated ARH-77 or KMS-11 tumors. This activity is observed in early and late disease stages of disseminated KMS-11 tumors and, in this model, the mechanism of antitumor activity is Fc-mediated, involving macrophages. As human IgG1 is the iso...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Identification of Different Form Tim-3 Proteins by a Unique Set of Tim-3 Monoclonal Antibodies
In this study, we have successfully developed a unique set of Tim-3 antibodies that are able to detect different molecular weights (by Western blot mobility) of Tim-3 proteins ectopically expressed in the same CHO cells. Some of the antibody clones detect only 33 or 55 kDa bands, the rest can recognize both 33 and 55 kDa bands on polyacrylamide gel electrophoresis gel. Antibody clones with 55 kDa specificity uniquely bind to the membrane form of Tim-3 on macrophage, which colocalizes with the CD68, and could be used as a specific marker for tumor-associated macrophage, whereas other clones showed cytoplasmic staining...
Source: Journal of Immunotherapy - February 1, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Nivolumab-induced Adrenal Insufficiency in Patients With Renal Cell Carcinoma
In conclusion, we described, for the first time, a case series of nivolumab-induced adrenal insufficiency in patients with mRCC. Our findings may be useful for the accurate diagnosis and the prompt treatment of this condition. In addition, there is a possibility that adrenal insufficiency may be associated with a favorable response to nivolumab in patients with mRCC. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Radiation Priming Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma With High Tumor Burden
This study demonstrates that radiotherapy is an optimal debulking regimen to managing R/R DLBCL patients before CAR-T therapy and a promising alternative salvage therapy for patients who suffer a relapse after CAR-T therapy by fuelling CAR-T copies. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Severe Acute Kidney Injury Due to Nivolumab/Ipilimumab-induced Granulomatosis and Fibrinoid Vascular Necrosis
Immune-checkpoint inhibitors have revolutionized the treatment of cancers in recent years. Four drugs have obtained FDA approval in a variety of cancer types. Immune-related adverse events are common and occur in up to 60% of treated patients. Common manifestations of immune-related adverse events include rash, colitis, hepatitis, and hypophysitis. Most cases are mild to moderate in grade; however, severe manifestations with lethal outcomes have been described. Acute kidney injury is reported as a rare complication. In this case report, we present a patient with metastatic melanoma undergoing combined immune-checkpoint inh...
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
CAIX-specific CAR-T Cells and Sunitinib Show Synergistic Effects Against Metastatic Renal Cancer Models
Treatment with chimeric antigen receptor-modified T cell (CAR-T) has demonstrated promising therapeutic efficacy in hematologic malignancies. However, the therapeutic efficacy is still very limited for solid tumors. An immunosuppressive microenvironment is one of the main reasons for the limited efficacy. Some chemotherapeutic agents exhibit immune microenvironment modulation. Therefore, combination with chemotherapeutic agents may be one of the promising strategies to enhance the therapeutic efficacy of CAR-T against solid tumors. Sunitinib modulates the antitumor immune response by improving T-cell infiltration and funct...
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Basic Study Source Type: research
Association of Insurance Status With Presentation, Treatment, and Survival in Melanoma in the Era of Immune Checkpoint Inhibitors
The effect of health insurance on management and outcomes in melanoma is unclear. Using the National Cancer Database (NCDB), we evaluated the effect of insurance on (1) stage at diagnosis, (2) receipt of immunotherapy, and (3) overall survival (OS) among patients with melanoma. We included patients with stage I–IV melanoma diagnosed from 2011 to 2015. Patients were stratified by age (below 65 vs. 65 y or above) and insurance (commercial, Medicare, Medicaid and uninsured). We evaluated the association between insurance and (1) stage at diagnosis (stage I–III vs. IV) and (2) receipt of immunotherapy (stage IV) using mu...
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Review Articles Source Type: research
Immune-related Adverse Events and Survival in Solid Tumors Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Immune-related adverse events (irAEs) are autoimmune-toxic effects associated with immune checkpoint inhibitors (ICIs) used for the treatment of advanced solid tumors. We performed a systematic review and meta-analysis of the published literature to assess the outcome for cancer patients treated with ICIs who develop irAEs. Two independent reviewers selected prospective or retrospective studies from PubMed, EMBASE, and the Cochrane Library database from their inception to November 2018. Data were pooled using hazard ratios (HRs) for overall survival or progression-free survival or odds ratio for overall response rate of ir...
Source: Journal of Immunotherapy - December 9, 2019 Category: Allergy & Immunology Tags: Review Articles Source Type: research
