scholarly journals Az onkológiában alkalmazott immuncheckpointgátló terápiák autoimmun mellékhatásai: patogenezis, klinikum és terápia

2019 ◽  
Vol 160 (23) ◽  
pp. 887-895
Author(s):  
Éva Szekanecz ◽  
Zoltán Szekanecz
Keyword(s):  
Side Effects ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Current View ◽  
Immune Mediated ◽  
Underlying Malignancy ◽  
Organ Specific ◽  
Checkpoint Inhibitor Therapy

Abstract: Oncotherapy has been revolutionised by the introduction of immune-checkpoint inhibitors including CTLA4, PD1 and PDL1 inhibitors. Patients with malignant diseases may largely benefit from these therapies, which may result in long-term remission even in the most therapy-resistant tumour types. Differences in the mode of action of the various agents may result in varying side-effect profiles. In addition to organ-specific side-effects, overt autoimmune syndromes may also develop. Our current view of oncotherapy has changed as these mostly immune-mediated side-effects highly differ from those observed previously during the administration of traditional anti-tumour compounds. These side-effects should be carefully characterized and differentiated from infections or the progression of the underlying malignancy. Fortunately, several recent recommendations have become available on the management of immune-mediated adverse events due to checkpoint-inhibitor therapy. Orv Hetil. 2019; 160(23): 887–895.

Long-term immune-related adverse events after discontinuation of immunotherapy

Immunotherapy ◽  
2021 ◽  
Author(s):  
Karoline Horisberger ◽  
Carmen Portenkirchner ◽  
Andreas Rickenbacher ◽  
Luc Biedermann ◽  
Christoph Gubler ◽  
...  
Keyword(s):  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Late Onset ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Symptomatic Therapy ◽  
Checkpoint Inhibitor Therapy ◽  
Severe Colitis

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and pembrolizumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

scholarly journals Releasing the brakes: a case report of pulmonary arterial hypertension induced by immune checkpoint inhibitor therapy

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402096096 ◽  
Author(s):  
Matthew Glick ◽  
Chase Baxter ◽  
David Lopez ◽  
Kashif Mufti ◽  
Stephen Sawada ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lupus Erythematosus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Checkpoint Inhibitor Therapy ◽  
Pulmonary Arterial

Immune checkpoint inhibitors successfully treat various malignancies by inducing an immune response to tumor cells. However, their use has been associated with a variety of autoimmune disorders, such as diabetes, hepatitis, and pneumonitis. Pulmonary arterial hypertension due to checkpoint inhibitor use has not yet been described. We present a novel case of pulmonary arterial hypertension associated with systemic lupus erythematosus and Sjogren’s syndrome overlap that was induced by therapy with the checkpoint inhibitor durvalumab.

Immune checkpoint inhibitor–associated hypercalcaemia

2020 ◽  
Author(s):  
Hassan Izzedine ◽  
Thibaud Chazal ◽  
Rimda Wanchoo ◽  
Kenar D Jhaveri
Keyword(s):  
Immune System ◽  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Endocrine Disease ◽  
Oncological Patients ◽  
Hyperprogressive Disease

Abstract Immune checkpoint inhibitors (CPIs) have recently become a cornerstone for the treatment of different advanced cancers. These drugs have the ability to reactivate the immune system against tumour cells but can also trigger a myriad of side effects, termed immune-related adverse events (irAEs). Although there are numerous reports of CPI-related endocrinopathies, hypercalcaemia as a suspected irAE is not well documented. The mechanisms of CPI hypercalcaemia are not clearly established. However, in our review, four distinct causes emerged: endocrine disease-related, sarcoid-like granuloma, humoral hypercalcaemia due to parathyroid-related hormone and hyperprogressive disease following CPI initiation. Prompt recognition of hypercalcaemia and the institution of therapy can be lifesaving, affording the opportunity to address the underlying aetiology. In this review we discuss the incidence, diagnosis and management of immune-related hypercalcaemia in oncological patients receiving CPI agents.

Ophthalmic adverse effects of immune checkpoint inhibitors: the Mayo Clinic experience

2020 ◽  
pp. bjophthalmol-2020-316970 ◽  
Author(s):  
Blake Hugo Fortes ◽  
Harris Liou ◽  
Lauren A Dalvin
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Immune Checkpoint ◽  
Ocular Surface ◽  
Side Effect ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Common Side Effect ◽  
Targeting Therapy

Background/AimsTo investigate immune-related ophthalmic side effects of systemic checkpoint inhibitors and compare side effect frequency and requirement for cessation of immunotherapy by checkpoint target.MethodsPatients taking immune checkpoint inhibitors at a single centre from January 1, 2010 to February 29, 2020 were retrospectively reviewed for clinical characteristics, treatments and concurrent systemic adverse effects.ResultsOf 996 patients, 28 (2.8%) experienced an ophthalmic side effect that came to the attention of an eye care provider. Mean age at presentation of the side effect was 63 years (median 64, range 25–88). The checkpoint inhibitor most often preceding side effects was pembrolizumab in 12 (43%). The most common side effect was dry eye in 16 (57%), followed by uveitis in 4 (14%) patients, and singular cases of ptosis and binocular diplopia, among others. Ocular surface adverse effects occurred more frequently with programmed death ligand-1 (PD-L1) targeting therapy. There were no significant differences in the frequency of orbit/ocular adnexa and uveitis or retinal side effects based on checkpoint targets. Follow-up was available in 13 (46%) patients, with mean duration of 20 months (median 16, range 2–52 months). Of these patients, the ophthalmic side effects were controlled without discontinuing therapy in 12 (92%). Checkpoint inhibitor cessation was required in one patient with panuveitis.ConclusionOphthalmic immune-related adverse events are rare but could be more common than previously estimated. PD-L1-directed checkpoint inhibitors may have a slight predilection for ocular surface adverse effects. Most ophthalmic events can be treated with targeted therapy without discontinuation of life-prolonging immunotherapy.

scholarly journals In Search of a Histopathological Pattern of Immune-Mediated Gastritis from Nivolumab Therapy: A Case Report with Literature Review

2021 ◽  
pp. 1-3
Author(s):  
Flor M Fernández-Gordón Sánchez ◽  
Flor M Fernández-Gordón Sánchez ◽  
Elena Gomez Dominguez ◽  
Cristina Garfia Castillo ◽  
Jorge Arroyo Andres ◽  
...  
Keyword(s):  
Case Report ◽  
Side Effects ◽  
Literature Review ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Gastrointestinal Symptoms ◽  
Specific Pattern ◽  
Immune Mediated ◽  
Upper Gastrointestinal Symptoms ◽  
Upper Gastrointestinal

Immunotherapy with checkpoint inhibitors is associated with termed inflammatory and immune-related side effects (irAE). Upper gastrointestinal symptoms are infrequent and appear mainly in patients on combination therapy with two checkpoint inhibitor drugs. We present the case of a patient with IIIB stage cutaneous melanoma treated with Nivolumab in monotherapy who developed an immune-mediated gastritis. Histopathologically, due to the paucity of published cases, no specific pattern of Nivolumab-immune-mediated gastritis has been described. We have reviewed the literature and compared the histopathology of the cases available in the literature.

scholarly journals Successful Treatment of an Immune-Mediated Colitis Induced by Checkpoint Inhibitor Therapy in a Patient with Advanced Melanoma

2020 ◽  
Vol 14 (3) ◽  
pp. 554-560
Author(s):  
Maria Paparoupa ◽  
Sophie Stupperich ◽  
Lisa Goerg-Reifenberg ◽  
Andreas Wittig ◽  
Frank Schuppert
Keyword(s):  
Malignant Melanoma ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Rescue Therapy ◽  
Diagnostic Colonoscopy ◽  
Immune Mediated ◽  
Remission Rates ◽  
Checkpoint Inhibitor Therapy ◽  
Ulcerative Lesions

Immune checkpoint inhibitors (ICIs) have been used as immunotherapeutic agents in several malignancies because of their ability to modify the T cell-mediated response against tumor cells. Dual checkpoint inhibition improves remission rates in patients with metastatic melanoma compared to monotherapy. However, a higher incidence of toxicity, including immune-related colitis, has been reported before. A 54-year-old female was diagnosed with malignant melanoma on her left upper arm. Because of progressive metastatic disease, a rescue therapy with nivolumab (Opdivo®) 1 mg/kg and ipilimumab (Yervoy®) 3 mg/kg was initiated and a clinical and radiological remission was achieved. Two weeks after completing the third cycle of the ICI therapy, the patient presented with persistent hemorrhagic diarrhea, nausea and abdominal pain. A diagnostic colonoscopy revealed multiple ulcerative lesions and hemorrhagic colitis of the sigmoid and rectum. Due to the ongoing treatment with nivolumab and ipilimumab, the diagnosis of a checkpoint inhibitor-induced colitis was made and immunosuppression with local and systemic steroids, such as mesalazine was initiated. In order to achieve a long-lasting steroids reduction, we decided to start with infliximab (Remicade® 5 mg/kg body weight i.v. every 2 weeks). Clinical remission was achieved and prednisolone could be subsequently discontinued. Infliximab, in combination with mesalazine, could successfully induce a long-lasting remission without steroids. The treatment of ICI-induced colitis did not lead to a reoccurrence of malignant melanoma after 2 years of follow-up.

scholarly journals Nivolumab-Induced Autoimmune Encephalitis in Two Patients with Lung Adenocarcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Suma Shah ◽  
Anastasie Dunn-Pirio ◽  
Matthew Luedke ◽  
Joel Morgenlander ◽  
Mark Skeen ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Standard Treatment ◽  
Patient Survival ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Autoimmune Encephalitis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Immune Mediated ◽  
Advanced Malignancies

Immune checkpoint inhibitors have improved patient survival outcomes in a variety of advanced malignancies. However, they can cause a number of immune-related adverse effects (irAEs) through lymphocyte dysregulation. Central nervous system (CNS) irAEs are rare, but as the number of indications for checkpoint inhibitors increases, there has been emergence of CNS immune-mediated disease among cancer patients. Given the relatively recent recognition of checkpoint inhibitor CNS irAEs, there is no standard treatment, and prognosis is variable. Therefore, there is a great need for further study of checkpoint inhibitor-induced CNS irAEs. Here, we present two unique cases of nivolumab-induced autoimmune encephalitis in patients with non-small cell lung cancer and review the available literature.

scholarly journals Immune checkpoint inhibitors as a bridge to allogeneic transplantation with posttransplant cyclophosphamide

2018 ◽  
Vol 2 (17) ◽  
pp. 2226-2229 ◽  
Author(s):  
Laura K. Schoch ◽  
Kenneth R. Cooke ◽  
Nina D. Wagner-Johnston ◽  
Ivana Gojo ◽  
Lode J. Swinnen ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Allogeneic Transplantation ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibition ◽  
Key Points ◽  
Checkpoint Inhibitor Therapy ◽  
Related Mortality

Key Points Checkpoint inhibition use before alloBMT followed by PTCy is not associated with increased aGvHD or transplant-related mortality/morbidity. Prior checkpoint inhibitor therapy should not be a contraindication to allogeneic transplantation, especially in the setting of PTCy.

scholarly journals Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside

2021 ◽  
Vol 12 ◽  
Author(s):  
Linda Wu ◽  
Venessa H. M. Tsang ◽  
Sarah C. Sasson ◽  
Alexander M. Menzies ◽  
Matteo S. Carlino ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Autoimmune Diabetes ◽  
Management Strategies ◽  
Therapeutic Strategies ◽  
Β Cell

Immune checkpoint inhibitors have transformed the landscape of oncological therapy, but at the price of a new array of immune related adverse events. Among these is β-cell failure, leading to checkpoint inhibitor-related autoimmune diabetes (CIADM) which entails substantial long-term morbidity. As our understanding of this novel disease grows, parallels and differences between CIADM and classic type 1 diabetes (T1D) may provide insights into the development of diabetes and identify novel potential therapeutic strategies. In this review, we outline the knowledge across the disciplines of endocrinology, oncology and immunology regarding the pathogenesis of CIADM and identify possible management strategies.

Angioedema late in the course of adjuvant nivolumab therapy for melanoma

2019 ◽  
Vol 26 (4) ◽  
pp. 1019-1021 ◽  
Author(s):  
Atul Ratra ◽  
Constantin A Dasanu
Keyword(s):  
Side Effects ◽  
Cancer Patients ◽  
Skin Rash ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Drug Withdrawal ◽  
Checkpoint Inhibitors ◽  
Full Resolution ◽  
Immune Mediated

Although immune checkpoint inhibitors improve survival in cancer patients, they have also been linked with unusual side effects. The most common side effects of these agents are immune-mediated phenomena such as itching, skin rash, arthralgias, mild transaminitis and asymptomatic thyroid dysfunction. We describe herein a case of facial angioedema occurring 20 weeks after initiating adjuvant nivolumab therapy for melanoma. The patient had full resolution of symptoms with cessation of nivolumab and a short steroid course. As the causality of an association between nivolumab and angioedema seems legitimate, we expect further similar cases to surface in patients treated with immune checkpoint inhibitors. Prompt drug withdrawal and steroids are crucial to ensure favorable clinical outcomes in these patients.

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