scholarly journals Use of immune checkpoint inhibitors in patients with solid tumors and pre-existing autoimmune or inflammatory disease: real-word data.

2020 ◽  
Author(s):  
Virginia Calvo ◽  
Marta Andrés Fernández ◽  
Ana Collazo Lorduy ◽  
Fernando Franco ◽  
Beatriz Núñez ◽  
...  
Keyword(s):  
Inflammatory Disease ◽  
Lupus Erythematosus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Autoimmune Diabetes ◽  
Autoimmune Hypothyroidism ◽  
Patients With Cancer ◽  
Latent Autoimmune Diabetes ◽  
Autoimmune Conditions

Abstract OBJECTIVE Immune checkpoint inhibitors (ICI) are a cornerstone in cancer treatment but they can induce immune-related adverse events (irAEs). Furthermore, patients with pre-existing autoimmune and/or inflammatory disease (AID) have been excluded from clinical trials. The objective of this study is to evaluate the efficacy and safety of ICI in patients with cancer and AID. METHODS This is an observational, retrospective study carried out at the Medical Oncology Department of Hospital Universitario Puerta de Hierro, Majadahonda, Madrid between January 2016 and December 2018. RESULTS 202 cancer patients treated with ICI were included, 15 (7, 4%) of them had pre-existing autoimmune diseases. The most frequent pre-existing AID were thyroid diseases (33.3%): autoimmune hypothyroidism, Graves Basedow disease and Hashimoto's thyroiditis. Three patients had psoriasis, two ANA + polyarthritis, one rheumatoid arthritis, another LADA (latent autoimmune diabetes in adults), another a systemic lupus erythematosus (SLE) and the last one, a polymyalgia rheumatica. In this series, the majority of patients (73.33%) did not experience any flare-up of their autoimmune disease. In patients who had AID flare-up, this was treated with corticosteroids. The most frequent cause of immunotherapy discontinuation was tumor progression (40%). 20% of patients had to discontinue immunotherapy due to toxicity. CONCLUSIONS In our series, AID flare or irAEs in patients with pre-existing AID who receive immunotherapy are not very common and can often be controlled without interrupting treatment. Prospective studies are needed to establish the incidence of irAEs in patients with preexisting autoimmune conditions, evaluate risk-benefits and elaborate management clinical guidelines in this population.

scholarly journals Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

2020 ◽  
Vol 21 (9) ◽  
pp. 3389 ◽  
Author(s):  
Konstantinos Melissaropoulos ◽  
Kalliopi Klavdianou ◽  
Alexandra Filippopoulou ◽  
Fotini Kalofonou ◽  
Haralabos Kalofonos ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Immune Checkpoint ◽  
Inflammatory Arthritis ◽  
Immune Checkpoint Inhibitors ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Musculoskeletal Complaints ◽  
Moderate Severity ◽  
Rheumatic Manifestations ◽  
New Onset

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. Their clinical efficacy is well-documented, but the side effects associated with their use are still under investigation. These drugs cause several immune-related adverse events (ir-AEs), some of which stand within the field of rheumatology. Herein, we present a literature review performed in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICIs. The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis. Non-musculoskeletal rheumatic manifestations are less frequent, with the most prominent being sicca, vasculitides and sarcoidosis. Cases of systemic lupus erythematosus or scleroderma are extremely rare. The majority of musculoskeletal ir-AEs are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation. In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed. Oncologists should periodically screen patients receiving ICIs for new-onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.

Age affects the efficacy of immune checkpoint inhibitors in patients with advanced cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2638-2638
Author(s):  
Yongjie Wang ◽  
Ronghua Yang ◽  
Dong Wang ◽  
Donghua Zhao ◽  
Peng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Older Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Sign Test ◽  
Patients With Cancer ◽  
The Impact ◽  
Effect Of Age

2638 Background: Immune checkpoint inhibitors (ICIs), such as programmed death(ligand)1 (PD-(L)1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, have dramatic effects on treatment in patients with various malignancies. High tumor mutation burden (TMB) is predictive of clinical response to ICI in multiple cancer types. Although age-related immune dysfunction might induce difference on the efficacy of ICIs between younger and older patients, the potential effect of age on the efficacy of ICIs remains little known and controversial. Herein, we aimed to analysis the association between age and the efficacy of ICIs based on MSKCC cohort. Methods: We screened out 1661 patients having complete information with advanced cancer, whose tumors underwent next-generation sequencing (NGS) detection and who were treated with at least one dose of ICI in MSKCC cohort. All patients were divided into two groups according to age, the younger group (age ≤50-year old) and the older group (age > 50-year old). We further analyzed the differences in overall survival (OS) and TMB between the two groups. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated via Cox regression model for OS and P-values were calculated via the Wilcoxon sign test for TMB. We analyzed the effect of age on ICI in lung cancer using the same way. Results: In 1661 patients with cancer in our study, 312 (19%) younger and 1349 (81%) older patients were found. The pooled HRs for OS was 1.28 (95% CI: 1.09-1.52) in younger group compared with older group. In 1661 patients with cancer, there was 350 (21%) patients with lung cancer, including 30 (9%) younger and 320 (91%) older patients. The pooled HRs for OS was 1.45 (95% CI: 0.95-2.23) in younger group compared with older group in lung cancer. In addition, TMB in older group was higher than in younger group and significant difference of TMB was found via the Wilcoxon sign test (p = 2.6e-10) between the two groups, especially in lung cancer (p = 1e-4). Conclusions: Our study assessed the impact of age on the efficacy of ICIs using the threshold of 50 years old for the first time and we founded that patients in older group had higher TMB and longer OS than younger group.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

2021 ◽  
pp. 1-11
Author(s):  
Deniz Can Guven ◽  
Oktay Halit Aktepe ◽  
Melek Seren Aksun ◽  
Taha Koray Sahin ◽  
Gozde Kavgaci ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patients With Cancer ◽  
Early Progression ◽  
Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

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.

scholarly journals Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

2020 ◽  
Vol 40 (3) ◽  
pp. 1219-1227 ◽  
Author(s):  
ONDREJ FIALA ◽  
ONDREJ SOREJS ◽  
JAN SUSTR ◽  
RADEK KUCERA ◽  
ONDREJ TOPOLCAN ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patients With Cancer

Immune-related adverse events associated with immune checkpoint inhibitors in patients with cancer

2020 ◽  
pp. 030089162095346
Author(s):  
Nilay Sengul Samanci ◽  
Duygu Ilke Cikman ◽  
Kerem Oruc ◽  
Sahin Bedir ◽  
Emir Çelik ◽  
...  
Keyword(s):  
Adverse Events ◽  
Health Care Providers ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Care Providers ◽  
Patients With Cancer ◽  
Combination Treatments ◽  
Grade 3

Introduction: With the widespread use of immune checkpoint inhibitors (ICIs), we are facing challenges in the management of immune-related adverse events (irAEs). We aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs. Methods: Patients who were treated with at least one ICI in clinical trials, expanded access programs, or routine clinical practice were included. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, methods of management, and treatment outcomes. Results: A total of 255 patients were screened retrospectively. Of these, 71 (27.8%) patients developed irAEs. More than 2 different types of irAEs were detected in 16 (6.2%) out of 255 patients. A total of 3177 doses were given to 255 patients. In 93 (2.9%) of the 3177 doses, 1 episode of irAEs was experienced. A total of 22 out of 93 (23.7%) episodes were reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most frequently seen irAEs were pneumonitis, hepatitis, and hypothyroidism. With regard to treatment, 39 out of 93 episodes (42%) of any grade irAEs occurred after anti–programmed cell death-1 therapy, 47 (50.5%) occurred following administration of anti–programmed death-ligand 1, and 7 (7.5%) occurred after combination treatments. Conclusion: With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology.

scholarly journals Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review

2019 ◽  
Vol 181 (3) ◽  
pp. 363-374 ◽  
Author(s):  
Jeroen M K de Filette ◽  
Joeri J Pen ◽  
Lore Decoster ◽  
Thomas Vissers ◽  
Bert Bravenboer ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Diabetic Ketoacidosis ◽  
Immune Checkpoint ◽  
Health Care Professionals ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Autoimmune Diabetes ◽  
Acid Decarboxylase ◽  
Close Monitoring

Objective To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs). Design and methods We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy. Results Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population. Conclusion ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.

scholarly journals Is there a role for physical activity when treating patients with cancer with immune checkpoint inhibitors? Protocol for a scoping review

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e046052
Author(s):  
Miaoqi Chen ◽  
Ridesh Raj ◽  
Louis Fox ◽  
Charlotte Louise Moss ◽  
Gincy George ◽  
...  
Keyword(s):  
Physical Activity ◽  
Scoping Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Physical Activities ◽  
Biological Mechanisms ◽  
Patients With Cancer ◽  
Oncological Outcomes ◽  
The Impact

IntroductionFor patients with cancer, immune checkpoint inhibitors (ICIs) produce superior long-term responses compared with alternative treatments, although at the cost of manifesting adverse immune-related events. There are many hypotheses of the impacts of physical activities in immunotherapy, but little is known about the oncological outcomes and the underlying mechanisms. This scoping review aims to identify possible physical activity interventions, their efficacy and feasibility and the potential underlying biological mechanisms responsible for their effects.Method and analysisThe Levac methodology framework was used along with guidance from the Joanna Briggs Institute Manual for Evidence Synthesis to inform development of this protocol. Abstracts and titles followed by full-text screening will be performed by two independent reviewers for inclusion. All studies describing the impact of physical activities and exercise interventions on cancer ICIs, with particular focus on oncological outcomes, quality of life or underling biological mechanisms, will be included. After extracting qualitative and quantitative data, they will be evaluated and summarised, respectively. Subsequently, a further consultation step with other scientists and healthcare professionals will be performed.Ethics and disseminationThe research findings will be published through an open-access peer-reviewed journal. The results of this scoping review will be used to inform further studies on physical impacts on immunotherapy. All data included will be from open resources, therefore, no ethical clearances are required.

scholarly journals Risk of tuberculosis in patients with cancer treated with immune checkpoint inhibitors: a nationwide observational study

2021 ◽  
Vol 9 (9) ◽  
pp. e002960
Author(s):  
Seongman Bae ◽  
Ye-Jee Kim ◽  
Min-ju Kim ◽  
Jwa Hoon Kim ◽  
Sung-Cheol Yun ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Exposure Group ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Insurance Claims Data ◽  
Health Insurance Claims Data

BackgroundWhile some recent studies have reported the development of tuberculosis (TB) in patients exposed to immune checkpoint inhibitors (ICIs), there is limited evidence to date. Therefore, we evaluated the risk of TB in patients with cancer exposed to ICIs using the National Health Insurance claims data in South Korea.MethodsPatients with diagnostic codes for non-small cell lung cancer, urothelial carcinoma or melanoma between August 2017 and June 2019 were identified. The incidence rate and standardized incidence ratio (SIR) of TB were calculated for both the ICI exposure and non-exposure groups. The risk of TB according to ICI exposure was assessed using a multivariable Cox regression model.ResultsDuring the study period, 141 550 patients with cancer and 916 new TB cases were identified. Among the 5037 patients exposed to ICIs, 20 were diagnosed with TB at a median of 2.2 months after the ICI was initiated. The crude incidence rate of TB per 100,000 person-years was 675.8 (95% CI 412.8 to 1043.8) for the ICI exposure group and 599.1 (95% CI 560.5 to 639.6) for the non-exposure group. The SIR for TB was 8.1 (95% CI 8.0 to 8.2) in the ICI exposure group. After adjusting for potential confounding factors, ICI treatment was not significantly associated with an increased risk of TB (HR: 0.73; 95% CI 0.47 to 1.14).ConclusionsWhile the incidence of TB in cancer patients exposed to ICIs was eightfold higher than in the general population, the risk of patients with cancer developing TB did not significantly differ according to ICI exposure.

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