Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 20594

Special Issue Editors

Head of Quick Diagnosis Unit, Department of Internal Medicine, Hospital Clínic, University of Barcelona School of Medicine, Villarroel 170, 08036 Barcelona, Spain
Interests: clinical diagnosis; medical alternatives to hospitalization; systemic autoimmune diseases
Department of Internal Medicine, Supportive and Palliative Care Unit in Cancer, Hospital Clinic, Villarroel 170, 08036-Barcelona, Spain
Interests: cancer; oncological emergencies; supportive care; autoimmune diseases; infectious diseases; critical care; vasculitis; immunotherapy; immune-related adverse events
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Special Issue Information

Dear Colleagues,

Biological therapies are being used since more than one decade in autoimmune diseases, targeting with synthetic molecules (antibodies, soluble receptors, cytokines, or cytokine antagonists) diverse pathways related to the immune response. Its use, in continuous expansion, is promising and has allowed physicians to deepen their understanding of the immune system and its signaling pathways. This knowledge has been transferred to the oncologic field.

Immunotherapy as a cancer treatment has represented a paradigm shift for patients suffering from many types of malignancies. Some patients experience incredible responses to these treatments, even in advanced cancer diseases, but others suffer from unexpected autoimmune aggressions triggered by immunotherapy. These are called immune-related adverse events, being sometimes life-threatening and still representing challenging situations which require a multidisciplinary approach. It is clear that further clinical and translational research is warranted. Prevention of immune-related adverse events, its diagnosis and treatment, and even more importantly, implications in the treatment of patients with cancer when adverse events occur are still issues that need to be clarified and approached by the scientific community.

The main aim of this Special Issue, titled “Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer”, is to provide useful and interesting knowledge to physicians who take care of cancer patients regarding immunotherapy treatment and its yet poorly known adverse events. Content about adverse events diagnosis and management related to biological therapies in the scenario of autoimmune diseases treatment would also be considered appropriate.

Dr. Xavier Bosch
Dr. Javier Marco-Hernández
Guest Editors

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Keywords

  • immunotherapy
  • immune-related adverse events (irAE)
  • cancer treatment
  • diagnosis
  • immune checkpoint inhibitors
  • immune oncology
  • toxicity

Published Papers (8 papers)

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Research

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14 pages, 3061 KiB  
Article
Imaging Findings in Patients with Immune Checkpoint Inhibitor-Induced Arthritis
Diagnostics 2022, 12(8), 1961; https://doi.org/10.3390/diagnostics12081961 - 13 Aug 2022
Cited by 5 | Viewed by 1686
Abstract
Immune checkpoint inhibitor (ICI)-induced arthritis is an increasingly recognized adverse event in patients with oncologic disease during immunotherapy. Four patterns are well described, including rheumatoid arthritis (RA)-like, polymyalgia rheumatica (PMR)-like, psoriatic arthritis (PsA)-like, and oligo-monoarthritis, among others. Despite better clinical recognition of these [...] Read more.
Immune checkpoint inhibitor (ICI)-induced arthritis is an increasingly recognized adverse event in patients with oncologic disease during immunotherapy. Four patterns are well described, including rheumatoid arthritis (RA)-like, polymyalgia rheumatica (PMR)-like, psoriatic arthritis (PsA)-like, and oligo-monoarthritis, among others. Despite better clinical recognition of these syndromes, information about the main imaging findings is limited. Methods: We conducted a retrospective observational study including all adult patients referred to the Rheumatology Department of a single-center due to ICI-induced arthritis who underwent imaging studies [ultrasound (US), magnetic resonance imaging (MRI), and 18F-FDG PET/CT)] between January 2017 and January 2022. Results: Nineteen patients with ICI-induced arthritis with at least one diagnostic imaging assessment were identified (15 US, 4 MRI, 2 18F-FDG PET/CT). Most patients were male (84.2%), with a median age at inclusion of 73 years. The main underlying diagnoses for ICI treatment were melanoma in five cases. The distribution of ICI-induced arthritis was as follows: PMR-like (5, 26.2%), RA-like (4, 21.1%), PsA-like (4, 21.1%), and others (6, 31.6%). All RA-like patients had US findings indistinguishable from conventional RA patients. In addition, 3/5 (60%) of PMR-like patients had significant involvement of the hands and wrists. Abnormal findings on MRI or PET-CT were reported by clinical symptoms. No erosions or myofascitis were seen. Conclusions: ICI-induced arthritis patients present inflammatory patterns on imaging studies similar to conventional inflammatory arthropathies, and therefore these syndromes should be followed carefully and treated according to these findings. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer)
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11 pages, 2573 KiB  
Article
Gastrointestinal Involvement in Dermatomyositis
Diagnostics 2022, 12(5), 1200; https://doi.org/10.3390/diagnostics12051200 - 11 May 2022
Cited by 4 | Viewed by 3395
Abstract
Dermatomyositis is a systemic vasculopathy mainly affecting skin, muscle and lung, but may affect the gastrointestinal tract. We aim to describe clinical characteristics of patients with severe gastrointestinal involvement related to dermatomyositis in our center and medical literature. We retrospectively analysed these patients [...] Read more.
Dermatomyositis is a systemic vasculopathy mainly affecting skin, muscle and lung, but may affect the gastrointestinal tract. We aim to describe clinical characteristics of patients with severe gastrointestinal involvement related to dermatomyositis in our center and medical literature. We retrospectively analysed these patients in our center, including cases of erosions/ulcers, perforation or digestive bleeding. Reported cases from April 1990 to April 2021 were reviewed through PubMed and Cochrane. From our cohort (n = 188), only 3 presented gastrointestinal compromise. All were women (10, 46 and 68 years). The initial symptom was abdominal pain and all had ≥2 episodes of digestive bleeding. All died due to complications of gastrointestinal involvement. Available pathological samples showed vascular ectasia. From the literature review (n = 50), 77% were women with a mean age of 49 years and the main symptom was abdominal pain (65%). All presented active muscular and cutaneous involvement at complication diagnosis. Mortality was 41.7%. The underlying lesion was perforation or ulcer (n = 22), intestinal wall thickening (n = 2), macroscopic inflammation (n = 2) or intestinal pneumatosis (n = 15). In 13 cases, vasculitis was described. Gastrointestinal involvement in dermatomyositis denotes severity, so an early intensive treatment is recommended. Pathological findings suggest that the underlying pathophysiological mechanism is a vasculopathy and not a true vasculitis. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer)
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Review

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17 pages, 320 KiB  
Review
Severe Immune-Related Adverse Events: A Case Series of Patients Needing Hospital Admission in a Spanish Oncology Referral Center and Review of the Literature
Diagnostics 2022, 12(9), 2116; https://doi.org/10.3390/diagnostics12092116 - 31 Aug 2022
Cited by 1 | Viewed by 1334
Abstract
Immune checkpoint inhibitors (ICI) have revolutionized the landscape of cancer treatment. Although several studies have shown that ICIs have a better safety profile than chemotherapy, some patients develop immune-related adverse events (irAEs), which require specialized and multidisciplinary management. Since ICI indications are rapidly [...] Read more.
Immune checkpoint inhibitors (ICI) have revolutionized the landscape of cancer treatment. Although several studies have shown that ICIs have a better safety profile than chemotherapy, some patients develop immune-related adverse events (irAEs), which require specialized and multidisciplinary management. Since ICI indications are rapidly increasing, it is crucial that clinicians involved in cancer care learn to identify irAEs and manage them properly. Here, we report a case series of 23 patients with severe irAEs requiring hospitalization over a period of 12 months and seize the opportunity to review and update different general features related to irAEs along with the management of the most frequent severe irAEs in our series. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer)
31 pages, 1046 KiB  
Review
Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy
Diagnostics 2022, 12(9), 2091; https://doi.org/10.3390/diagnostics12092091 - 29 Aug 2022
Cited by 5 | Viewed by 4576
Abstract
Immunotherapy has dramatically changed the therapeutic landscape of oncology, and has become standard of care in multiple cancer types in front or late lines of therapy, with some longstanding responses and outstanding results. Notwithstanding, its use has brought a totally unique spectrum of [...] Read more.
Immunotherapy has dramatically changed the therapeutic landscape of oncology, and has become standard of care in multiple cancer types in front or late lines of therapy, with some longstanding responses and outstanding results. Notwithstanding, its use has brought a totally unique spectrum of adverse events, characterized by a myriad of diverse manifestations affecting nearly every organ and system of the body, including the endocrine, nervous, cardiac, respiratory and gastrointestinal systems. Uncommon adverse events, defined as those occurring in less than 1% of patients, comprise an even more heterogeneous group of diseases that are being seen more recurrently as the use of immune check-point inhibitors increases and indications spread in different tumor types and stages. Here, we comprehensively review some uncommon, but exceedingly important, immune-related adverse events, with special emphasis in the clinical approach and diagnostic workup, aiming to reunite the evidence published previously, allowing an increase in awareness and knowledge from all specialists implicated in the diagnosis, treatment, and care of cancer patients treated with immunotherapy. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer)
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Other

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5 pages, 1005 KiB  
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Reversible Tumor Progression Induced by a Dexamethasone Course for Severe COVID-19 during Immune Checkpoint Inhibitor Treatment
Diagnostics 2022, 12(8), 1933; https://doi.org/10.3390/diagnostics12081933 - 10 Aug 2022
Cited by 1 | Viewed by 1481
Abstract
Immunotherapies and immune checkpoint inhibitors (ICI) represent the latest revolution in oncology. Several studies have reported an association between the use of corticosteroids and poorer outcomes for patients treated with ICIs. However, it has been never established whether corticoid-induced tumor progression under ICI [...] Read more.
Immunotherapies and immune checkpoint inhibitors (ICI) represent the latest revolution in oncology. Several studies have reported an association between the use of corticosteroids and poorer outcomes for patients treated with ICIs. However, it has been never established whether corticoid-induced tumor progression under ICI treatment could be reversible. We report herein transient tumor progression induced by dexamethasone for a patient treated with pembrolizumab for metastatic bladder cancer. An 82-year-old man was treated with pembrolizumab as a second-line treatment for metastatic urothelial carcinoma with stable disease for 8 months as the best tumoral response. He experienced severe coronavirus disease 2019 (COVID-19) infection and was treated with high-dose dexamethasone for ten days according to the RECOVERY protocol. Following this episode, radiological CT-scan evaluation showed tumor progression. Pembrolizumab was maintained, and subsequent radiological evaluation showed tumor shrinkage. This case highlights that the antagonistic effect of glucocorticoids with ICI efficacy is transient and can be reverted when corticoids are withdrawn. Clinicians should be aware that tumor progression in the context of the intercurrent use of systemic corticosteroids can be temporary and should be interpreted with caution, and ICI continuation could be considered for some patients. Insights: The antagonistic effect of glucocorticoids with ICI efficacy is transient and can be reverted when corticoids are withdrawn. Tumor progression in the context of the intercurrent use of systemic corticosteroids can be temporary and should be interpreted with caution, and ICI continuation could be considered for some patients. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer)
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8 pages, 2350 KiB  
Case Report
A Rare Case of Hepatic Vanishing Bile Duct Syndrome Occurring after Combination Therapy with Nivolumab and Cabozantinib in a Patient with Renal Carcinoma
Diagnostics 2022, 12(2), 539; https://doi.org/10.3390/diagnostics12020539 - 19 Feb 2022
Cited by 2 | Viewed by 1755
Abstract
Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) significantly improve the outcomes of patients with advanced clear cell renal cell carcinoma (ccRCC); however, high-grade toxicities can occur, particularly during combination therapy. Herein, we report a patient with advanced metastatic ccRCC, who developed [...] Read more.
Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) significantly improve the outcomes of patients with advanced clear cell renal cell carcinoma (ccRCC); however, high-grade toxicities can occur, particularly during combination therapy. Herein, we report a patient with advanced metastatic ccRCC, who developed grade 4 cholestasis during combined therapy with nivolumab and cabozantinib. After the exclusion of common disorders associated with cholestasis and a failure of corticosteroids (CS), a liver biopsy was performed that demonstrated severe ductopenia. Consequently, a diagnosis of vanishing bile duct syndrome related to TKI and ICI administration was made, resulting in CS discontinuation and ursodeoxycholic acid administration. After a 7-month follow-up, liver tests had returned to normal values. Immunological studies revealed that our patient had developed robust T-cells and macrophages infiltrates in his lung metastasis, as well as in skin and liver tissues at the onset of toxicities. At the same time, peripheral blood immunophenotyping revealed significant changes in T-cell subsets, suggesting their potential role in the pathophysiology of the disease. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer)
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7 pages, 4068 KiB  
Case Report
Vedolizumab Attenuates Immune-Checkpoint-Therapy-Induced Infliximab-Refractory Colitis
Diagnostics 2022, 12(2), 480; https://doi.org/10.3390/diagnostics12020480 - 13 Feb 2022
Cited by 5 | Viewed by 1740
Abstract
Immune checkpoint inhibitors (ICIs), such as nivolumab and ipilimumab, have drastically changed treatments of advanced melanoma. However, ICI-related enterocolitis is often the most common adverse event, and represents the main reason for ICI discontinuation and mortalities. Here, we report the case of a [...] Read more.
Immune checkpoint inhibitors (ICIs), such as nivolumab and ipilimumab, have drastically changed treatments of advanced melanoma. However, ICI-related enterocolitis is often the most common adverse event, and represents the main reason for ICI discontinuation and mortalities. Here, we report the case of a metastatic melanoma treated with vedolizumab for ICI-induced colitis. A 67-year-old man treated with ipilimumab and nivolumab developed ICI-induced colitis and grade 3 diarrhea refractory to methylprednisolone and infliximab. After his third dose of vedolizumab, oral prednisolone ceased, and the colitis had completely resolved with no recurrence. This case report supports vedolizumab use in treating severe colitis which failed to resolve with first- and second-line immunosuppressive therapy. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer)
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15 pages, 3067 KiB  
Case Report
Oral Candida Infection in Psoriatic Patients Treated with IL17A Inhibitors: Report of 3 Cases and a Comprehensive Review of the Literature
Diagnostics 2022, 12(1), 3; https://doi.org/10.3390/diagnostics12010003 - 21 Dec 2021
Cited by 3 | Viewed by 3406
Abstract
An intact and fully functional immune system plays a crucial role in the prevention of several infectious diseases. Interleukin (IL)17 is significantly involved in oral mucosa immunity against several antigens and microorganisms, including Candida albicans (CA). Herein, we present three cases of oral [...] Read more.
An intact and fully functional immune system plays a crucial role in the prevention of several infectious diseases. Interleukin (IL)17 is significantly involved in oral mucosa immunity against several antigens and microorganisms, including Candida albicans (CA). Herein, we present three cases of oral candidiasis (OC) related to the use of an IL17A inhibitor for psoriasis. Three psoriatic individuals presented for evaluation of widespread symptomatic oral lesions temporally correlated with the onset of IL17A inhibitors (secukinumab in two patients and brodalumab in one patient). Clinical examination revealed either partially removable white plaques in an erythematous background (case #1) or diffuse erythematous lesions (cases #2 and 3) involving several areas of the oral mucosa. Cytology smear, accompanied by histopathologic examination in case #1, confirmed the clinical impression of OC in all three cases. All patients received antifungal therapy with satisfactory clinical response. No discontinuation of the antipsoriatic regimen was recommended, but all patients were advised to remain under monitoring for possible OC relapses. During the last few years, new systemic biologic agents targeting IL17 have been used for the management of variable immune-mediated diseases. Few clinical trials and scarce case reports have shown that these medications place individuals at high risk of developing candidiasis. We propose that patients treated with these medications should be at close monitoring for the development of OC and, if it occurs, receive appropriate management. Full article
(This article belongs to the Special Issue Immune-Related Adverse Events Diagnosis and Immunotherapy in Cancer)
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