Reader Comment Regarding "Cutaneous Immune-Related Adverse Events (irAEs) to Immune Checkpoint Inhibitors: A Dermatology Perspective on Management".
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ABSTRACT:
SUBMITTER: Sauder M
PROVIDER: S-EPMC8750150 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1/PD-L1) antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.
| S-EPMC5296331 | biostudies-literature
Project description:IntroductionCurrent epidemiologic literature of rheumatologic immune-related adverse events (rh-irAEs) consists of clinical trials, case reports, or smaller, single-center series. We evaluate the occurrence of rh-irAEs during immune checkpoint inhibitor (ICI) therapy from US commercial claims data.MethodsPatients newly initiating ICI therapy in commercial claims data were eligible for inclusion. Rh-irAEs were defined using ≥ 1 International Classification of Diseases (ICD)-9 or ICD-10-Clinical Modification (CM) claims for selected events, ranging from joint pain and myalgia to ankylosing spondylitis and psoriasis. The percentage of patients experiencing rh-irAEs after ICI initiation was determined.ResultsA total of 5722 patients initiating an ICI between January 1, 2012, and June 30, 2018, were included; 201 patients (3.5%) had a history of rheumatic disease. Among the 5521 patients without a history of rheumatic disease, 29.6% experienced ≥ 1 rh-irAE in follow-up, decreasing to 22.6% when assessing events for which there was no diagnostic history. Limiting to claims for rh-irAE with a rheumatologist provider, the proportion of patients experiencing an event decreased to 0.9%. Among patients with a history of rheumatic disease, 71.6% experienced ≥ 1 rh-irAE. Limiting to events for which the patient did not have a history during baseline, 35.3% experienced an event.ConclusionsOccurrence of rh-irAEs during ICI use is higher in patients with pre-existing rheumatic disease compared to those with no pre-existing rheumatic disease. However, the most common events were not definitive rheumatic diseases but rather symptoms, such as pain in joints. Occurrence of events associated with a rheumatologist provider was substantially lower, suggesting that either patients are not referred to a rheumatologist or referral does not result in confirmation of the diagnosis by the rheumatologist.
| S-EPMC8572292 | biostudies-literature
Project description:Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, 25 to ≤30, ≥30 kg/m2). The outcome of interest was irAEs after ICI initiation. A multivariable logistic regression model estimated the adjusted odds ratio (aOR) and 95% confidence interval (CI) of BMI. A total of 684 patients with stage III or IV cancer were included in the study (lung: 269, melanoma: 204, other: 211). The mean age at the first dose of ICI was 64.1 years (SD = 13.5), 394 patients (57.6%) were male, and over one-third (N = 260, 38.0%) were non-White. Overall, 52.9% of patients had BMI ≥ 25 kg/m2 (25 to ≤30: 217, ≥30: 145) and 288 (42.1%) had irAEs after ICI treatment. Patients with higher BMI tended to have a higher rate of irAEs (<25: 35.7%, 25 to ≤30: 47.0%, ≥30: 49.0%). The multivariable logistic regression yielded consistent results (BMI ≥ 30 vs. BMI < 25: aOR = 1.47, 95% CI = 0.96-2.23; 25 ≤ BMI < 30 vs. BMI < 25: aOR = 1.46, 95% CI = 1.02-2.11, p-trend = 0.04). In conclusion, among patients with advanced cancer receiving ICIs, the rate of irAEs appears to be higher among those with higher BMI.
| S-EPMC8657283 | biostudies-literature
Project description:As the incidence of cutaneous malignancies continues to rise and their treatment with immunotherapy expands, dermatologists and their patients are more likely to encounter immune checkpoint inhibitors. While the blockade of immune checkpoint target proteins (cytotoxic T-lymphocyte-associated protein-4, programmed cell death-1, and programmed cell death ligand-1) generates an antitumor response in a substantial fraction of patients, there is a critical need for reliable predictive biomarkers and approaches to address refractory disease. The first article of this Continuing Medical Education series reviews the indications, efficacy, safety profile, and evidence supporting checkpoint inhibition as therapeutics for metastatic melanoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Pivotal studies resulting in the approval of ipilimumab, pembrolizumab, nivolumab, cemiplimab, and avelumab by regulatory agencies for various cutaneous malignancies, as well as ongoing clinical research trials, are discussed.
| S-EPMC7572574 | biostudies-literature
Project description:BackgroundNonphysicians are expanding practice into specialty medicine. There are limited studies on patient and physician perspectives as well as safety outcomes regarding the nonphysician practice of cosmetic procedures.ObjectiveTo identify the patient (consumer) and physician perspective on preferences, adverse events, and outcomes following cosmetic dermatology procedures performed by physicians and nonphysicians.Materials and methodsInternet-based surveys were administered to consumers of cosmetic procedures and physician members of the American Society for Dermatologic Surgery. Descriptive statistics and graphical methods were used to assess responses. Comparisons between groups were based on contingency chi-square analyses and Fisher exact tests.ResultsTwo thousand one hundred sixteen commenced the patient survey with 401 having had a cosmetic procedure performed. Fifty adverse events were reported. A higher number of burns and discoloration occurred in the nonphysician-treated group and took place more often in a spa setting. Individuals seeing nonphysicians cited motivating factors such as level of licensure (type) of nonphysician, a referral from a friend, price, and the location of the practitioner. Improper technique by the nonphysician was cited most as a reason for the adverse event. Both groups agree that more regulation should be placed on who can perform cosmetic procedures. Recall bias associated with survey data.ConclusionPatients treated by nonphysicians experienced more burns and discoloration compared with physicians, and they are encountering these nonphysicians outside a traditional medical office, which are important from a patient safety and regulatory standpoint. Motivating factors for patients seeking cosmetic procedures may also factor into the choice of provider.Key pointsBoth patients and physicians think more regulation should be in place on who can perform cosmetic procedures. More adverse events such as burns and discolorations occurred with patients seeing nonphysicians compared with those seeing physicians. In addition, for those seeing nonphysicians, a majority of these encounters took place in spa settings. Patient safety is of utmost concern when it comes to elective cosmetic medical procedures. More adverse events and encounters occurring outside traditional medical settings when nonphysicians performed these procedures call into question the required training and oversight needed for such procedures.
| S-EPMC6450566 | biostudies-literature
Project description:Thymic carcinoma is a rare neoplasm with a dismal prognosis, and there are no established therapeutic regimens for metastatic or recurrent disease. Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, are widely approved in several human cancers, contributing to prolonging survival in thoracic tumors. Thymic carcinoma exhibits histologic properties of squamous cell carcinoma (SQC), and resembles the SQC of the lung. ICIs are not approved in thymic carcinoma. Thus, several clinical trials have been undertaken to demonstrate if they are therapeutically effective for patients with thymic carcinoma. In our review, three prospective phase II studies and several case series were discussed in thymic carcinoma. We found that the objective response rate, disease control rate, and progression-free survival in PD-1 blockade monotherapy were approximately 20%, 73%, and four months, respectively. Two exploratory investigations indicated that PD-L1 within tumor cells exhibits a possibility of the therapeutic prediction of PD-1 blockade in thymic carcinoma. Several case reports, alongside their treatment content, have also been reviewed. The therapeutic efficacy of PD-1 blockade monotherapy is still limited in patients with thymic carcinoma. Future perspectives focus on the therapeutic implication of tyrokinase inhibitors plus ICIs or new experimental agents plus ICIs alongside several ongoing experimental studies.
| S-EPMC7959131 | biostudies-literature
Project description:BackgroundThe incidence of cutaneous melanoma (CM) is increasing, and its prognosis is not optimistic. Although immune checkpoint (ICP) inhibitors are effective in the treatment of CM patients, they are not effective for all CM patients. There is an urgent need for a marker to predict both the prognosis and the immunotherapy effect in patients with CM.ApproachesTwo groups of patients with greatly different prognosis and response to immunotherapy were identified by unwatched cluster exploration of TCGA on the basis of 34 ICPs. The prognosis and immunotherapy effect of CM were predicted by developing a precise and given signature on the basis of ICPs, and a multivariate Cox risk regression model was established from the TCGA cohort consisting of 454 CM samples. The model was validated in 210 and 231 samples in the test and verification cohorts, respectively.ResultsThe prognosis in clinical subgroups was predicted by the classification system. High-risk patients had poorer responses to chemotherapy and immunotherapy. Finally, the signature was recognized as an independent prognostic factor. Based on checkpoint-based signature (ICPBS) and clinical characteristics, we constructed a nomogram for the prognosis in patients with CM, which was superior to ICPBS in efficacy than ICPBS alone.ConclusionAs a useful prognostic tool to further improve cancer immunotherapy, the signature can accurately predict recurrence and overall survival among patients with CM.
| S-EPMC8738081 | biostudies-literature
Project description:IL-6 is a cytokine that plays an important role in response to injury or infection and is a promising biomarker for predicting poor prognosis and therapeutic targets in non-small cell lung cancer (NSCLC). This article reviews the biochemical mechanism, function and genotype of IL-6, and summarizes the diagnostic and prognostic value of IL-6 level. Anti-IL-6 therapy does not affect the effect of immunocheckpoint inhibitors (ICIs), but enhances its anticancer function, which may be the treatment option for immune-related adverse events (irAEs) in the future. Therefore, IL-6 may be a therapeutic target for the treatment of NSCLC.
| S-EPMC7113041 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs), which target the programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4 signaling pathways, represent remarkable breakthroughs in cancer treatment and have improved survival among patients with a variety of malignancies. However, the wide use of ICIs is associated with a spectrum of immune-related adverse events (irAEs) that can affect any organ system, and may sometimes be life threatening. Rheumatic irAEs are not an infrequent type of irAE. In this systematic review, we consider the clinical characteristics of rheumatic irAEs, including patients with pre-existing rheumatic diseases, and focus on the management of rheumatic irAEs.
| S-EPMC6938753 | biostudies-literature
Project description:Immune-modulatory therapy, especially with immune-checkpoint inhibitors (ICIs), has reshaped cancer therapeutics. Immunotherapy is relatively a novel approach that can effectively delay the progression of aggressive tumors and inhibit tumor recurrence and metastasis in many different tumor types. In the past years, ICIs have shown a sustained response and promising long-term survival in patients with advanced hepatocellular carcinoma (HCC). Nevertheless, ICI therapy can unbalance the immune system and result in a wide range of immune-related adverse events (irAEs), which are generally manageable but occasionally lead to a fatal outcome. HCC generally develops in the context of liver cirrhosis which is typically caused by viral hepatitis and non-alcoholic steatohepatitis. These underlying diseases may cause symptoms that overlap with irAEs and lead to consequences such as late recognition, inadequate work-up, and inappropriate treatment. Owing to the growing use of immunotherapy in HCC, it is necessary for clinicians to strengthen their understanding of the frequency, clinical features, and management of irAEs. This review focuses on the common toxicities associated with ICI therapy in patients with HCC and summarizes therapeutic strategies that can be used to monitor and manage such toxicities.
| S-EPMC7678689 | biostudies-literature