Immunotherapy Utilization Among Patients With Metastatic NSCLC: Impact of Comorbidities
In patients with metastatic non–small cell lung cancer (mNSCLC), the extent to which immunotherapy utilization rate varies by comorbidities is unclear. Using the National Cancer Database from 2015 to 2016, we assessed the association between levels of comorbidity and immunotherapy utilization among mNSCLC patients. Burden of comorbidities was ascertained based on the modified Charlson-Deyo score and categorized as an ordinal variable (0, 1, and ≥2). Immunotherapy utilization was determined based on registry data. Multivariable logistic regressions were used to estimate adjusted odds ratios (aOR) and 95% confidence inte...
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Sudden Otovestibular Dysfunction in 3 Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibitors
We describe detailed diagnostic work-up and therapeutic interventions and discuss possible pathogenic mechanisms of this rare and disabling event. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Baseline Plasma Inflammatory Profile Is Associated With Response to Neoadjuvant Chemotherapy in Patients With Pancreatic Adenocarcinoma
Despite its increased application in pancreatic ductal adenocarcinoma (PDAC), complete response to neoadjuvant therapy (NAT) is rare. Given the critical role of host immunity in regulating cancer, we sought to correlate baseline inflammatory profiles to significant response to NAT. PDAC patients receiving NAT were classified as responders (R) or nonresponders (NR) by carbohydrate antigen 19-9 response, pathologic tumor size, and lymph node status in the resected specimen. Baseline (treatment-naive) plasma was analyzed to determine levels of 27 inflammatory mediators. Logistic regression was used to correlate individual med...
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Cancer Therapeutics–related Cardiac Dysfunction in Patients Treated With Immune Checkpoint Inhibitors: An Understudied Manifestation
The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an ab...
Source: Journal of Immunotherapy - May 20, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
A Multicentre Retrospective Analysis of Toxicity in 6-weekly Versus 3-weekly Pembrolizumab
We present real-world comparative toxicity data. Patients receiving pembrolizumab for any indication between March and December 2019 were included across 3 regional centers. Toxicity data were collected retrospectively using Common Terminology Criteria for Adverse Events, v5.0. Clinically significant immune-related adverse events (CSirAE) were defined as immune-related events and grade ≥3 rash. Data were analyzed using incidence (Poisson distribution) and incidence ratio. Overall, 63 patients started on q6w and 110 patients received q3w. There were 3 (q6w) and 8 (q3w) grade 3–5 CSirAE and 13 (q6w) and 31 (q3w) grade 1...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Impact of Baseline Corticosteroids on Immunotherapy Efficacy in Patients With Advanced Melanoma
This is a 2-center, retrospective study which aimed to evaluate the effect of baseline corticosteroid use on immunotherapy efficacy in patients with advanced melanoma. We included all patients with advanced unresectable and metastatic melanoma on single-agent programmed cell death protein 1 (PD-1) inhibitors at the Cancer Centre of Southeastern Ontario and London Regional Cancer Program. We defined baseline corticosteroid use as prednisone-equivalent of ≥10 mg within 30 days of immunotherapy initiation. Our study had 166 patients in total, and 25 were taking corticosteroids at the initiation of the PD-1 inhibitor. Base...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Anti-PD1 Immunotherapy for Metastatic Renal Cancer Boosted Humoral Immunity In a Hemodialysis Patient
Immune checkpoint inhibitors by blocking specific inhibitory pathways induce T-cell-mediated tumor lysis. However, many remain to be elucidated about their effect on human humoral immunity. We evaluated the effect of the PD1 inhibitor nivolumab on humoral immunity by following the levels of antibodies against hepatitis B surface antigen (anti-HBs) in a hemodialysis patient successfully vaccinated against hepatitis B virus 5 years ago and now starting nivolumab for renal cell carcinoma lung metastases. Anti-HBs kinetics after administration of an extra vaccine dose were also evaluated. Nivolumab increased anti-HBs and facil...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Cardiac Troponin I and T in Checkpoint Inhibitor–associated Myositis and Myocarditis
Checkpoint inhibitor–associated myocarditis (ir-myocarditis) and myositis (ir-myositis) may occur concurrently among patients on checkpoint inhibitor immunotherapy. While cardiac-specific troponin I (cTnI) and troponin T (cTnT) are regarded to have similar sensitivities and specificities in conditions such as acute coronary syndrome, the cardiac specificity of cTnT has been challenged following observation that patients with neuromuscular diseases, including myositis, may have elevated cTnT without apparent clinical evidence of myocardial injury. Consequently, in the context of concurrent ir-myositis, cTnI may be a more ...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Branched Multipeptide-combined Adjuvants Potentially Improve the Antitumor Effects on Glioblastoma
The promising immunotherapy effects of a multiple antigenic peptide on glioblastoma (GBM) in a previous study encourage the use of adjuvants to enhance its therapeutic efficacy. Among adjuvants, pan HLA-DR-binding epitope (PADRE) and anti-programmed cell death protein 1 (anti-PD1) have potentially been tested for cancer immunotherapy. Therefore, here we evaluated the ability of PADRE and anti-PD1 to enhance the function of the branched multipeptide against GBM. The potential utility of tumor-associated antigens (ErbB-2 and WT-1) targeting GBM with HLA-A24 was confirmed and a branched multipeptide was constructed from these...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Identification of HLA-A*0201-restricted CTL Epitopes for MLAA-34-specific Immunotherapy for Acute Monocytic Leukemia
Our previous research has shown that monocytic leukemia–associated antigen-34 (MLAA-34) was a novel antiapoptotic molecule with unique expression in acute monocytic leukemia (M5), making it an ideal target for T-cell–based immunotherapy. Here, we sought to identify HLA-A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope of MLAA-34 by reverse immunology. In all, 10 HLA-A*0201 restricted epitopes of MLAA-34 were predicted by bioinformatics. MLAA-34324–332, MLAA-34293–301, and MLAA-34236–244 showed the strongest HLA-A*0201-binding affinity. The percentages of HLA-A*0201-MLAA-34236–244 tetramer+ CD8+ T cells in ...
Source: Journal of Immunotherapy - April 16, 2021 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors
There have been unique adverse events reported with targeted blockade of programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA4), including immune mediated toxicities. Recently, there have been reports of hepatitis B reactivation (HBVr) occurring with PD-1/PD-L1 inhibitors, which may result in treatment delays, interruptions, or discontinuation. This retrospective literature review and analysis of the Food and Drug Administration’s (FDA) Adverse Events Reporting System (FAERS) queried reported cases of “Hepatitis B reactivation” reported with the PD-1/PD-L...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Incidence and Prediction of Immune Checkpoint Inhibitor-related Nephrotoxicity
Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events that can affect any organ system, including the kidneys. Our study aimed to better characterize the incidence of and predictive factors for immune-related acute kidney injury (irAKI) and evaluate steroid responsiveness. An institutional database (Carolina Data Warehouse) was queried for patients who received ICIs and subsequently had substantial AKI, defined as a doubling of baseline creatinine. A retrospective chart review was performed to determine the cause of AKI. AKI events determined to be immune-related were further analyzed. A total of 1766...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Carpal Tunnel Syndrome: A New Adverse Effect of Immune Checkpoint Inhibitors, 11 Cases
This study aims at reporting 11 cases of carpal tunnel syndrome (CTS) occurring in patients on immunotherapy. The increasing use of immune checkpoint inhibitors in oncodermatology is associated with the appearance of immunologic adverse effects linked to nonspecific stimulation of the immune system. CTS has not been reported in this context. A retrospective multicenter review was performed on CTSs occurring on immunotherapy and confirmed with electroneuromyography. Data were collated from patients’ files. Most of the time, CTS was severe, bilateral, with a motor deficit and confirmed axonal damage on electroneuromyograph...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Checkpoint Inhibitor-associated Cutaneous Small Vessel Vasculitis: A Review of the Literature
Checkpoint inhibitor therapy is an established cancer treatment option often complicated by the development of immune-related adverse events. Vasculitis has been reported with a broad spectrum of both cutaneous and systemic manifestations and can be complicated by delayed diagnosis. The authors report 2 histologically proven cases of cutaneous leucocytoclastic vasculitis induced by programmed cell-death 1 inhibitor inhibitor nivolumab. As physicians, including medical oncologists and dermatologists, we need to be aware of this clinical entity and the importance of clinicopathological confirmation in this setting to confirm...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Immune Checkpoint Inhibitor-induced Bilateral Vestibulopathy
We present a severe case of CPI-related ongoing and most likely irreversible bilateral vestibular affection. A 59-year-old male melanoma patient with brain metastasis undergoing immunotherapy with anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death-1 antibodies developed severe debilitating rotatory vertigo. Bilateral vestibulopathy was diagnosed as a result of the CPI therapy after a thorough analysis including magnetic resonance imaging, laboratory tests of blood and cerebrospinal fluid as well as neurological and otorhinolaryngology examinations. The vertigo improved slightly during a 10-day course of steroi...
Source: Journal of Immunotherapy - March 18, 2021 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
