scholarly journals Immuno-related endocrinopathy in patients treated with immune checkpoint inhibitors

2020 ◽  
pp. 16-24
Author(s):  
D. I. Yudin ◽  
K. K. Laktionov ◽  
K. A. Sarantseva ◽  
O. I. Borisova ◽  
V. V. Breder ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Clinical Practice ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Serious Adverse Events ◽  
Immune Mediated ◽  
Discontinuation Of Treatment ◽  
The Russian Federation

Recently immune checkpoint inhibitors amazingly changed the landscape of cancer therapy worldwide. The number of immune checkpoint molecules in clinical practice is constantly increasing. There are some monoclonal antibodies recently registered in the Russian Federation: anti-PD1 antibodies (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab). Immune-mediated endocrinopathies are some of the most common complications of immunotherapy. According to the results of clinical studies, the incidence of serious endocrine immuno-mediated adverse events with anti-PD1 monoclonal antibodies is low (3.5–8%). The use of anti-CTLA4 antibodies, combined regimens, and the use of immunotherapy after chemoradiotherapy significantly increase the incidence of serious adverse events to 30%. In clinical practice of N.N. Blokhin Cancer Research Center among 245 non-small cell lung cancer and hepatocellular carcinoma patients treated with immunotherapy, 22 (8,9%) developed an immune-mediated endocrinopathy. Most patients developed adverse events of 1–2 degrees, in two patients – 3 degrees, requiring discontinuation of treatment. The aim of this article was to provide useful information and recommendations regarding the management of common immuno-related endocrine adverse events (including hypothyroidism, hyperthyroidism, pituitary, adrenal insufficiency) for clinical oncologists.

Pathogenesis, Clinical Manifestations and Management of Immune Checkpoint Inhibitors Toxicity

2017 ◽  
Vol 103 (5) ◽  
pp. 405-421 ◽  
Author(s):  
Alessandro Inno ◽  
Giulio Metro ◽  
Paolo Bironzo ◽  
Antonio M. Grimaldi ◽  
Elisabetta Grego ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Manifestations ◽  
Know How ◽  
Immune Mediated ◽  
Medical Oncologists ◽  
Tumor Types

Immune checkpoint inhibitors have emerged as an effective treatment for several tumor types and their use in clinical practice is expected to further increase in the immediate future. Although these agents are well tolerated, they are associated with a peculiar spectrum of toxicity, which is immune mediated and may potentially affect every organ. However, immune-related adverse events are mostly reversible if promptly diagnosed and adequately treated. Therefore, it is crucial that medical oncologists know how to diagnose and treat immune-related adverse events. This review focuses on the pathogenesis, clinical manifestations and management of immune-related toxicity of anti-CTLA-4 and anti-PD-1 antibodies.

scholarly journals Management of pulmonary toxicity associated with immune checkpoint inhibitors

2019 ◽  
Vol 28 (154) ◽  
pp. 190012 ◽  
Author(s):  
Myriam Delaunay ◽  
Grégoire Prévot ◽  
Samia Collot ◽  
Laurent Guilleminault ◽  
Alain Didier ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Pulmonary Toxicity ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Serious Adverse Events ◽  
Programmed Cell Death 1 ◽  
Life Threatening

Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible serious adverse events. Although severe immune-related adverse events remain rare, they can lead to discontinued treatment or to death if they are not forecasted and managed properly. Even if lung toxicity is not the most frequent adverse event, it remains critical as it can be life-threatening. Herein, the main aspects of pulmonary toxicity are reviewed and guidelines are also proposed in order to manage the possible side-effects.

scholarly journals Immune-mediated adverse events in immune checkpoint inhibitors therapy: literature review

2021 ◽  
Vol 23 (2) ◽  
pp. 319-326
Author(s):  
Marina A. Lyadova ◽  
Vladimir K. Lyadov
Keyword(s):  
Adverse Events ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acute Interstitial Nephritis ◽  
Early Symptom ◽  
Immune Mediated ◽  
Cutaneous Rash ◽  
Pancreatic Dysfunction

Immune-mediated adverse events (imAEs) are complications of therapy with immune checkpoint inhibitors, which arise as a result of autoimmune inflammation. The article summarizes systemic (fatigue, fever), cutaneous (rash, itching), gastrointestinal (diarrhea, colitis, hepatitis, pancreatic dysfunction), endocrinological (hypothyroidism, hypophysitis, adrenal insufficiency, diabetes mellitus), pulmonary (pneumonitis, pleuritis), rheumatological (arthralgia), neurological (headache, sensory and motor disorders), renal (acute interstitial nephritis, lupus-like nephritis, granulomatous nephritis, diffuse interstitial nephritis and minimal change disease), hematological (anemia, cytopenia), cardiovascular (myocarditis) and ocular (conjunctivitis, episcleritis, ceratitis, blepharitis and uveitis) imAE. Pathogenetic mechanisms and treatment approaches (in accordance with toxicity grade and clinical recommendations) are discussed. Early symptom recognition, patient education and timely intervention are crucial for imAE correction.

scholarly journals SARS-CoV-2 infection and adverse events in patients with cancer receiving immune checkpoint inhibitors: an observational prospective study

2021 ◽  
Vol 9 (2) ◽  
pp. e001694
Author(s):  
Mario Mandala ◽  
Paul Lorigan ◽  
Matilde De Luca ◽  
Andrea Bianchetti ◽  
Barbara Merelli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Antigen Expression ◽  
Serious Adverse Events ◽  
Exact Test ◽  
Cancer Subtypes ◽  
Patients With Cancer

BackgroundIn ambulatory patients with cancer with asymptomatic or pauci-symptomatic SARS-CoV-2 infection, the safety of targeted therapies (TTs), chemotherapy (CT) or immune checkpoint inhibitors (ICIs) therapy is still unknown.Material and methodsFrom the start of the first epidemic wave of SARS-CoV-2 in Bergamo, Italy, we have prospectively screened all consecutive outpatients who presented for treatment to the Oncology Division of the Papa Giovanni XXIII Hospital, Bergamo for SARS-CoV-2 antigen expression. We identified patients treated with ICIs and compared these to patients with the same cancer subtypes treated with TTs or CT.ResultsBetween March 5 and May 18, 293 consecutive patients (49% melanoma, 34% non-small cell lung cancer, 9% renal cell carcinoma, 8% other) were included in this study: 159 (54%), 50 (17%) and 84 (29%) received ICIs, CT or TTs, respectively. Overall 89 patients (30.0%) were SARS-CoV-2 positive. Mortality of SARS-CoV-2-positive patients was statistically significantly higher compared with SARS-CoV-2 negative patients (8/89 vs 3/204, respectively, Fisher’s exact test p=0.004). All deaths were due to COVID-19. Serious adverse events (SAEs) were more frequent in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative cases (Cochran-Mantel-Haenszel (CMH) test p=0.0008). The incidence of SAEs in SARS-CoV-2 positive compared with SARS-CoV-2 negative patients was similar in ICI and CT patients (17.3% and 3.7% for positive and negative patients in ICIs and 15.4% and 2.7% in CT, Breslow-Day test p=0.891). No COVID-19-related SAEs were observed in the TTs patients.ConclusionsThe incidence of SAEs was higher for SARS-CoV-2-positive patients treated with ICIs and CT, mostly in advanced disease. No SAEs were observed in patients treated with TTs. SAEs were COVID-19 related rather than treatment related. Treatment with ICIs does not appear to significantly increase risk of SAEs compared with CT. This information should be considered when determining treatment options for patients.

scholarly journals An Evaluation of the Use of Corticosteroids for the Management of Immune-Mediated Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Adrian Tsui, PharmD ◽  
Linday Edmondson, PharmD, BCOP ◽  
Justin Julius, PharmD
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Prescribing Practices ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Secondary Endpoints

Immune checkpoint inhibitors (ICIs) have gained prominence for the treatment of a variety of malignancies. However, they are associated with the development of immune-mediated adverse events (IMAEs). Appropriate management of IMAEs and subsequent rechallenging of patients with ICI therapy remains an important area of research. The primary endpoint of this study was to evaluate the efficacy of current prescribing practices and adherence to guideline recommendations for IMAE management. The incidence of symptom resolution, number of patients reinitiated with ICI therapy, and IMAE recurrence upon ICI therapy reinitiation were explored as secondary endpoints. A retrospective chart review within the Allegheny Health Network was conducted in cancer patients treated with ICI therapy who developed a documented ICI-associated IMAE and subsequently received corticosteroid therapy. IRB approval was obtained for this study. Descriptive statistics were used to analyze both primary and secondary endpoints. The study sample was made up of 81 patients. Overall, 50 out of 81 patient cases (62%) were found to be discordant with guideline recommendations; the primary factors identified were inappropriate starting corticosteroid dosing (64%), initiation of a corticosteroid taper prior to IMAE resolution to at least grade 1 severity, and condensed corticosteroid taper (74%). The main IMAEs identified were colitis (28%), pneumonitis (27%), and skin-related inflammation (12%). 76 out of the 81 patients (94%) achieved IMAE resolution; 41 patients (54%) were rechallenged with ICI therapy, of which 14 patients (34%) developed IMAE recurrence. Future studies may focus on evaluating different immunosuppression strategies to optimize IMAE management.

scholarly journals Treatment-Related Serious Adverse Events of Immune Checkpoint Inhibitors in Clinical Trials: A Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Ouyang ◽  
Yanyan Cao ◽  
Xuefeng Kan ◽  
Lei Chen ◽  
Yanqiao Ren ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
English Language ◽  
Checkpoint Inhibitors ◽  
Serious Adverse Events ◽  
Comprehensive Information ◽  
Grade 3

BackgroundImmune Checkpoint Inhibitors (ICI) have been progressively used in cancer treatment and produced unique toxicity profiles. This systematic review aims to comprehend the patterns and occurrence of treatment-related adverse events (trAEs) based on ICI.MethodsPICOS/PRISMA methods were used to identify published English-language on PubMed, Web of Science, and Scopus from 2015 to 2020. Published clinical trials on ICI monotherapy, combined ICIs, and ICI plus other treatment with tabulated data on grade≥3 trAEs were included. Odds ratio (OR), χ2 tests were used to analyze for effect size and associations.ResultsThis review included 145 clinical trials involving 21786 patients. Grade 3-5 trAEs were more common with ICI when they were plused with other treatments compared with ICI monotherapy(54.3% versus 17.7%, 46.1%, p<0.05). Grade 3-5 trAEs were also more common with CTLA-4 mAbs compared with anti-PD-1 and anti-PD-L1 (34.2% versus 15.1%, 13.6%, p<0.05). Hyperthyroidism (OR 3.8, 95%CI 1.7–8.6), nausea (OR 3.7, 95%CI 2.5–5.3), diarrhea (OR 2.7, 95%CI 2.2–3.2), colitis (OR 3.4, 95%CI 2.7–4.3), ALT increase (OR 4.9, 95%CI 3.9–6.1), AST increase (OR 3.8, 95%CI 3.0–4.9), pruritus (OR 2.4, 95%CI 1.5–3.9), rash (OR 2.8, 95%CI 2.1–3.8), fatigue (OR 2.8, 95%CI 2.2–3.7), decreased appetite (OR 2.4, 95%CI 1.5–3.8), and hypophysitis (OR 2.0, 95%CI 1.2–3.3) were more frequent with combined ICIs. Diarrhea (OR 8.1, 95%CI 6.4–10.3), colitis (OR 12.2, 95%CI 8.7–17.1), ALT increase (OR 5.1, 95%CI 3.5–7.4), AST increase (OR 4.2, 95%CI 2.8–6.3), pruritus (OR 4.1, 95%CI 2.0–8.4), rash (OR 4.4, 95%CI 2.9–6.8), hypophysitis (OR 12.1, 95%CI 6.3–23.4) were more common with CTLA-4 mAbs; whereas pneumonitis (OR 4.7, 95% CI 2.1–10.3) were more frequent with PD-1 mAbs.ConclusionsDifferent immune checkpoint inhibitors are associated with different treatment-related adverse events profiles. A comprehensive data in this systematic review will provide comprehensive information for clinicians.

scholarly journals IMMUNE-MEDIATED ADVERSE EVENTS ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITORS THERAPY

2016 ◽  
pp. 68-76 ◽  
Author(s):  
E. V. Reutova ◽  
K. P. Laktionov ◽  
V. V. Breder ◽  
K. A. Sarantseva ◽  
M. A. Okruzhnova ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Mediated

Immune-mediated adverse events following influenza vaccine in cancer patients receiving immune checkpoint inhibitors

2019 ◽  
Vol 26 (3) ◽  
pp. 647-654 ◽  
Author(s):  
Morgan E Gwynn ◽  
David L DeRemer ◽  
Katherine M Saunders ◽  
Jigarkumar Parikh ◽  
Roni J Bollag ◽  
...  
Keyword(s):  
Adverse Events ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Immune Checkpoint ◽  
Medical Records ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patient Questionnaire ◽  
Immune Mediated ◽  
Increased Risk

Objectives The emergence of immune checkpoint inhibitors has transformed treatment paradigms for various malignancies. Patients with cancer are at increased risk of complications and hospitalizations from influenza; therefore, it is recommended that they receive inactivated influenza vaccination. However, efficacy and safety of inactivated influenza vaccination in patients receiving immune checkpoint inhibitors is uncertain. The objective of this prospective case series was to evaluate the incidence of immune-mediated adverse events (imAEs) following inactivated influenza vaccination in patients receiving immune checkpoint inhibitors. Changes in cytokine and chemokine levels were also evaluated. Methods Patients receiving immune checkpoint inhibitors during the 2017–2018 influenza season were eligible for study participation. Peripheral blood samples were collected prior to administration of inactivated influenza vaccine and two post-vaccination time points. Evaluation of new or worsening imAEs occurred via patient questionnaire and review of medical records for 60 days following inactivated influenza vaccination. Baseline imAEs were evaluated from review of medical records for 60 days prior to inactivated influenza vaccination. Serum cytokines and chemokines were measured using a multiplex Luminex assay. Results Twenty-four patients were enrolled in this study. Seven patients experienced any grade imAE (one patient having 2) within 60 days following inactivated influenza vaccination. The majority were Grades 1–2, including rash ( n = 3), hypothyroidism, myalgia, and colitis ( n = 1 each). Two patients experienced severe imAEs (grade 3 nephritis and grade 4 diabetes). No significant changes ( p > 0.05) in serum cytokine or chemokine concentrations were observed. Conclusions Although small, our study suggests that inactivated influenza vaccine may be safely administered to patients receiving immune checkpoint inhibitors. The majority of imAEs following inactivated influenza vaccination were Grades 1-2 and did not require changes in immune checkpoint inhibitor therapy.

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