scholarly journals A case report of psoriasis flare following immunotherapy: Report of an important entity and literature review

2020 ◽  
Vol 8 ◽  
pp. 2050313X1989770 ◽  
Author(s):  
Anastasia Politi ◽  
Dimas Angelos ◽  
Davide Mauri ◽  
George Zarkavelis ◽  
George Pentheroudakis
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Skin Lesions ◽  
Inflammatory Disorder ◽  
Immune Mediated ◽  
Programmed Death ◽  
History Of ◽  
Programmed Death 1 ◽  
Cessation Of Treatment

Immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed death-1, are a type of cancer immunotherapy approved for late-stage malignancy treatment. However, such therapies often induce immune-related adverse events. During anti-programmed death-1 blockade therapy, the most commonly reported adverse effects are skin toxicities, such as psoriasis—a chronic immune-mediated inflammatory disorder affecting the skin. We present the clinical characteristics of flared psoriasis in one patient under anti-programmed death-1 therapy who was diagnosed with T2N2M0/IIIB squamous lung carcinoma with a history of psoriasis for the past 5 years, exacerbated after the first cycle of nivolumab. After the third cycle, the extensive skin plaques necessitated treatment cessation. Following the discontinuation of anti-programmed death-1 treatment, skin lesions were treated locally. Possibly, anti-programmed death-1 immunotherapy can trigger immune-mediated diseases, such as psoriasis. Physicians should be alert to immune-related adverse events. Continuation or permanent cessation of treatment depends on the severity and reversibility of immune-related adverse events.

scholarly journals Acute kidney injury from immune checkpoint inhibitor use

2019 ◽  
Vol 12 (10) ◽  
pp. e231211 ◽  
Author(s):  
Lexis Gordon ◽  
Pouneh Dokouhaki ◽  
Kimberly Hagel ◽  
Bhanu Prasad
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Programmed Death ◽  
Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

scholarly journals Kidney injury associated with antitumor therapy: focus on the adverse events of modern immuno-oncological drugs

2021 ◽  
Vol 93 (6) ◽  
pp. 649-660
Author(s):  
Elena S. Kamyshova ◽  
Irina N. Bobkova ◽  
Marina I. Sekacheva
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Inhibitory Effect ◽  
Immune System Activation ◽  
Programmed Death ◽  
Programmed Death Protein 1 ◽  
System Activation ◽  
New Generation

Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death protein 1 (PD-1) or its ligand (PD-L1), are a new generation of immuno-oncological drugs that to date have demonstrated efficacy in a number of malignancies. The mechanism of ICT inhibitors action consist in the potentiation of the immune response by eliminating the tumor cells inhibitory effect on the T-lymphocytes activation. However, excessive immune system activation can cause the development of a special class of immune-related adverse events (irAEs) involved a wide variety of organs and systems, including the kidneys. Despite the fact that immuno-mediated kidney injury caused by ICI therapy develops quite rarely, it can be serious and determine the patient's prognosis, which necessitates early diagnosis and timely start of treatment. In this regard, awareness of the manifestations of ICI-associated renal irAEs is particularly relevant not only for oncologists and for nephrologists, but for doctors of other specialties. In this review, we elucidated the main variants of immuno-mediated kidney injury caused by ICI therapy, discussed possible predictors and mechanisms of their development, and considers the general principles of diagnosis and management of patients according to the severity of irAEs.

scholarly journals Advancing the Management of Non-small Cell Lung Cancer

2017 ◽  
Vol 13 (01) ◽  
pp. 53
Author(s):  
David F Fakih ◽  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Personalised Therapy

Advances in the development of targeted therapies and immunotherapy have transformed the management of non small-cell lung cancer (NSCLC). Targeting angiogenesis and molecular drivers of carcinogenesis has led to the approval of several new therapies. More recently, immunotherapeutic approaches have been investigated in the treatment setting of NSCLC. These include immune checkpoint inhibitors (e.g. anti-cytotoxic T-lymphocyte antigen-4 [CTLA-4], anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 [PD-L1] agents). The emergence of so many therapeutic options offers the potential for personalised therapy. Molecular profiling can inform treatment decisions but there is a need for more data to determine the optimal sequencing and combination of targeted and immunotherapeutic agents.

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab

2020 ◽  
pp. 107815522092154
Author(s):  
Nikhila Kethireddy ◽  
Steffi Thomas ◽  
Poorva Bindal ◽  
Prateek Shukla ◽  
Upendra Hegde
Keyword(s):  
Type 1 Diabetes ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Polymyalgia Rheumatica ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Close Monitoring ◽  
Programmed Death ◽  
Programmed Death 1

Introduction Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes. Case report We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation. Management and outcome: Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation. Discussion Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.

scholarly journals T follicular helper cells: linking cancer immunotherapy and immune-related adverse events

2021 ◽  
Vol 9 (6) ◽  
pp. e002588
Author(s):  
Dirk Baumjohann ◽  
Peter Brossart
Keyword(s):  
Adverse Events ◽  
Cancer Immunotherapy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Underlying Mechanism ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Programmed Death ◽  
Cancer Types ◽  
Cell Death Protein

Cancer immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of numerous cancer types. As the underlying mechanism of these treatments lies in the interference with inhibitory signals that usually impair potent antitumor immunity, for example, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein 1 (PD-1):programmed death-ligand 1/2 (PD-L1/2) pathway, it is not surprising that this could also promote exaggerated adaptive immune responses to unrelated antigen specificities. One of the side effects of ICI-based cancer immunotherapy that is increasingly observed in the clinic is immune-related adverse events (irAEs), including various types of autoimmunity. However, the precise etiology is incompletely understood. T follicular helper (Tfh) cells provide essential help to B cells for potent antibody responses and their tumor tissue presence is often correlated with a better outcome in several solid tumor entities. Importantly, these CD4+ T cells express very high amounts of PD-1 and other co-stimulatory and inhibitory receptors. Here, we address the hypothesis that targeting CTLA-4 or PD-1 and its ligand PD-L1 critically impacts the function of Tfh cells in patients that receive these ICIs, thereby providing a link between ICI treatment and the development of secondary autoimmunity.

scholarly journals Prognostic impact of immune-related adverse events on patients with and without cardiovascular disease: a retrospective review

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shingo Kazama ◽  
Ryota Morimoto ◽  
Yuki Kimura ◽  
Naoki Shibata ◽  
Reina Ozaki ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Adverse Events ◽  
Retrospective Review ◽  
Proportional Hazards ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Limited Information ◽  
History Of

Abstract Background The emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in cancer treatment as the use of these drugs has become more frequent and for a longer duration. As a result of T-cell-mediated inflammation at the programmed cell death-1, programmed death-ligand-1, and cytotoxic T-lymphocyte antigen-4 pathways, immune-related adverse events (irAEs) occur in various organs and can cause a rare but potentially induced cardiotoxicity. Although irAEs are associated with the efficacy of ICI therapy and better prognosis, there is limited information about the correlation between irAEs and cardiotoxicity and whether the benefits of irAEs apply to patients with underlying cardiovascular disease. This study aimed to investigate the association of irAEs and treatment efficacy in patients undergoing ICI therapy with and without a cardiovascular history. Methods We performed a retrospective review of the medical records of 409 consecutive patients who received ICI therapy from September 2014 to October 2019. Results Median patient age was 69 years (29.6% were female). The median follow-up period was 278 days. In total, 69 (16.9%) patients had a history of any cardiovascular disease and 14 (3.4%) patients experienced cardiovascular irAEs after ICI administration. The rate of cardiovascular irAEs was higher in patients with prior non-cardiovascular irAEs than without. The prognosis of patients with irAEs ( +) was significantly better than that of the patients without irAEs (P < 0.001); additionally, this tendency did not depend on the presence or absence of a cardiovascular history. Furthermore, the Cox proportional hazards analysis revealed that irAEs were an independent predictor of mortality. Conclusions Although cardiovascular irAEs may be related to prior non-cardiovascular irAEs under ICI therapy, the occurrence of irAEs had a better prognostic impact and this tendency was not affected by cardiovascular history.

scholarly journals New emerging targets in cancer immunotherapy: the role of TIM3

ESMO Open ◽  
2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. e000497 ◽  
Author(s):  
Alex Friedlaender ◽  
Alfredo Addeo ◽  
Giuseppe Banna
Keyword(s):  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Lung Cancer Patients ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Cancer Types ◽  
Domain 3

Currently, the programmed death-1/programmed death ligand-1 and the cytotoxic T-lymphocyte-associated protein 4 are the two commonly targeted immune-checkpoint inhibition pathways. These drugs have significantly improved the prognosis of many cancer types. While immune-checkpoint inhibitors have revolutionised the treatment of many cancer types, the majority of patients still progress. Several treatment strategies have been pursued to improve current results. One approach is to combine two checkpoint inhibitors, currently with promising results in melanoma, renal cell carcinoma and a subset of non-small-cell lung cancer patients. The identification of new checkpoint targets could allow the field of immuno-oncology to evolve further. We will discuss one of the most promising immune-checkpoint targets currently under investigation, the T-cell immunoglobulin and mucin domain-3.

scholarly journals How we treat neurological toxicity from immune checkpoint inhibitors

ESMO Open ◽  
2019 ◽  
Vol 4 (Suppl 4) ◽  
pp. e000540 ◽  
Author(s):  
Lavinia Spain ◽  
Zayd Tippu ◽  
James M Larkin ◽  
Aisling Carr ◽  
Samra Turajlic
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Treatment Strategies ◽  
Presenting Symptoms ◽  
Programmed Death ◽  
Symptoms And Signs ◽  
Substantial Morbidity

Neurological adverse events from immune checkpoint inhibition are increasingly recognised, especially with combination anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) and anti-programmed death receptor 1 (anti-PD-1) therapies. Their presenting symptoms and signs are often subacute and highly variable, reflecting the numerous components of the nervous system. Given the risk of substantial morbidity and mortality, it is important to inform patients of symptoms that may be of concern, and to assess any suspected toxicity promptly. As with other immune-related adverse events, the cornerstone of management is administration of corticosteroids. Specialist neurology input is vital in this group of patients to guide appropriate investigations and tailor treatment strategies.

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