Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors

Background:The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.Objective:To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.Method:English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.Results:The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.Conclusion:Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.

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Prevalence of dermatological toxicities in patients with melanoma undergoing immunotherapy: Systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0255716 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0255716

Author(s):

Náthali Felícia Mineiro dos Santos Garrett ◽

Ana Cristina Carvalho da Costa ◽

Elaine Barros Ferreira ◽

Giovanni Damiani ◽

Paula Elaine Diniz dos Reis ◽

...

Keyword(s):

Systematic Review ◽

Side Effects ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Cutaneous Toxicity ◽

Cutaneous Side Effects ◽

Final Sample

Background Checkpoint inhibitors have revolutionized advanced melanoma care; however, their cutaneous side effects have not been definitively elucidated. Objective To identify the prevalence of cutaneous toxicity in patients with melanoma treated with immune checkpoint inhibitors as monotherapy and/or in combination with chemotherapy and/or radiotherapy. Materials and methods We performed a systematic review and meta-analysis, which encompassed both clinical trials and observational studies describing the dermatological toxicities in patients treated with immune checkpoint inhibitors. The protocol was registered in the International Prospective Register of Systematic Review under the number CRD42018091915. The searches were performed using the CINAHL, Cochrane CENTRAL, LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases. The methodological quality of the studies was evaluated with the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data Results A total of 9,802 articles were identified in the databases. The final sample comprised 39 studies. The evaluated drugs were ipilimumab, tremelimumab, pembrolizumab, and nivolumab. The results suggest that the most prevalent side effect was grade 1 and 2 pruritus (24%), followed by grade 1 and 2 rash (21%) and grade 1 and 2 vitiligo (10%). Conclusion The most prevalent side effects in patients treated with checkpoint inhibitors are pruritus, rash, and vitiligo, and they are rated mostly as grades 1 and 2 adverse events. Remarkably, vitiligo is most commonly found in patients treated with PD-1 inhibitors.

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Immune checkpoint inhibitor–associated hypercalcaemia

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa326 ◽

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.

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

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-316970 ◽

2020 ◽

pp. bjophthalmol-2020-316970 ◽

Cited By ~ 1

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.

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Management of Gastrointestinal Side Effects of Immune Checkpoint Inhibitors

Clinical Gastroenterology and Hepatology ◽

10.1016/j.cgh.2021.06.038 ◽

2021 ◽

Author(s):

Rashid N. Lui ◽

Stephen L. Chan

Keyword(s):

Side Effects ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Gastrointestinal Side Effects

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Side effects and management in immunotherapy based on immune checkpoint inhibitors

World Chinese Journal of Digestology ◽

10.11569/wcjd.v28.i16.755 ◽

2020 ◽

Vol 28 (16) ◽

pp. 755-764

Author(s):

Wen-Yu Li ◽

Ling-Chang Li ◽

Jie-Ge Huo

Keyword(s):

Side Effects ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors

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Evaluation of tolerability and reactions of immune checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e14605 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e14605-e14605 ◽

Cited By ~ 2

Author(s):

Ozlem Nuray Sever ◽

Ozlem Sonmez ◽

Osman Gokhan Demir

Keyword(s):

Monoclonal Antibodies ◽

Side Effects ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Treatment Interruption ◽

Ease Of Use ◽

Treatment Change ◽

Function Test ◽

Cessation Of Treatment

e14605 Background: Immunotherapies have revolutionized the treatment of cancer, especially in recent years. Today, there are anti-CTLA-4 antibodies and PD-L1 monoclonal antibodies which are active in use as checkpoint inhibitors. Side effects of these agents have a different spectrum in the form of immuno-related side effects. Methods: In this study, we aimed to evaluate the side effect and tolerability in patients treated with immune checkpoint inhibitors in our clinic. Results: 32 patients who were treated with PD-L1 monoclonal antibodies between August 2015 and January 2017 were screened retrospectively in our clinic. Six of the cases had immuno-related side effects (18.75%). 2 patients had a elevated liver function test. Both patients were diagnosed with NSCLC. In both of them, elevation was detected in the second course of nivolumab treatment, and the USG and hepatitis markers of the patients were normal. Enzymes returned to normal after treatment interruption. In a patient diagnosed with malignant melanoma that receiving pembrolizumab colitis was developed after 3th cycles of the therapy. The treatment of the patient who recovered after steroid administration and treatment interruption continued until the 8th cure. In the third cure of the patient with NSCLC, when nivolumab was used pneumonitis was diagnosed. Steroid treatment was applied for 2 weeks. Our patient continued to use nivolumab for up to 22 cycles. In our patient with malign melanoma that treated with pembrolizumab autoimmune thyroiditis developed. We started prednisolone treatment. After recovery our patient's treatment continued. In one of our patient who was diagnosed with malign melanoma, after the second cure of the treatment, diffuse edema and shortness of breath due to heart failure was detected. Echocardiography revealed a low ejection fraction. Methylprednisolone was started by cessation of treatment. Control ejection fractions normalized. Conclusions: İmmuno-related side effects were regarded as manageable side effects and no treatment change was needed. Immune Checkpoint inhibitors, which have been shown to be useful for survival every day, are proceeding to take a favorable position in the treatment of cancer with ease of use and lack of side effects.

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Side effects of extended interval dosing of checkpoint inhibitors among patients during COVID-19 pandemic at the Moncton and the Miramichi hospitals.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e14550 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e14550-e14550

Author(s):

Mahmoud Abdelsalam ◽

Rana Sughayar ◽

Glenn Myers ◽

Mrudula Avileli ◽

Maged Salem

Keyword(s):

Lung Cancer ◽

Side Effects ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Low Dose ◽

Checkpoint Inhibitors ◽

Future Research ◽

Important Data ◽

Dosing Schedule

e14550 Background: Since the COVID-19 pandemic started, managing cancer patients who are more vulnerable than the rest of the population has been a concern. One of the strategies to decrease cancer patient visits to the Oncology Clinic was by the use of an extended dosing schedule of immune checkpoint inhibitors. The goal of the present study is to record and describe patients’ experiences with irAEs on the modified treatment schedules. Methods: The study included cancer patients getting their treatment at the cancer care clinics at The Moncton Hospital and the Miramichi Hospital, and who switched to receiving either a modified dose of Pembrolizumab or Durvalumab. These participants were asked to complete a short survey that covered important data in their diagnosis and treatment, as well as the type of cancer diagnosed and which drug they were prescribed for treatment. Participants were also asked about the presence of any possible immune-related symptoms from a list of possible AEs since their last treatment visit, and to indicate (A) how often the symptom was experienced, and (B) how severe the symptom was. Results: Twenty-one patients filled out the questionnaire half of whom were females. Most of the patients had lung cancer and were on pembrolizumab. All the patients interviewed developed at least one new symptom after the change in the dose was introduced. The most frequent symptoms reported were itchy skin and fatigue and they were severely experienced. However, very few of the symptoms experienced required a physician consult or hospitalization. Most of the participants welcomed the change in the dose to protect them from COVID-19 and were mainly indifferent as to whether they get the low dose more frequently or the higher dose less frequently. Conclusions: This study has highlighted the frequency and severity of irAEs with the use of extended dosing schedule of immune checkpoint inhibitors. Future research should have more patients to validate this outcome and look for the causes behind the increased incidence and severity of irAEs with higher dose less frequent intervals of these immunotherapies.[Table: see text]

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