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.

scholarly journals Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Pan Shen ◽  
Xuan Deng ◽  
Zhishuo Hu ◽  
Zhe Chen ◽  
Yao Huang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Manifestations ◽  
Multidisciplinary Cooperation ◽  
Rheumatic Manifestations ◽  
Underlying Mechanisms

Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.

scholarly journals Rethinking immune checkpoint blockade: ‘Beyond the T cell’

2021 ◽  
Vol 9 (1) ◽  
pp. e001460 ◽  
Author(s):  
Xiuting Liu ◽  
Graham D Hogg ◽  
David G DeNardo
Keyword(s):  
Immune System ◽  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

The clinical success of immune checkpoint inhibitors has highlighted the central role of the immune system in cancer control. Immune checkpoint inhibitors can reinvigorate anti-cancer immunity and are now the standard of care in a number of malignancies. However, research on immune checkpoint blockade has largely been framed with the central dogma that checkpoint therapies intrinsically target the T cell, triggering the tumoricidal potential of the adaptive immune system. Although T cells undoubtedly remain a critical piece of the story, mounting evidence, reviewed herein, indicates that much of the efficacy of checkpoint therapies may be attributable to the innate immune system. Emerging research suggests that T cell-directed checkpoint antibodies such as anti-programmed cell death protein-1 (PD-1) or programmed death-ligand-1 (PD-L1) can impact innate immunity by both direct and indirect pathways, which may ultimately shape clinical efficacy. However, the mechanisms and impacts of these activities have yet to be fully elucidated, and checkpoint therapies have potentially beneficial and detrimental effects on innate antitumor immunity. Further research into the role of innate subsets during checkpoint blockade may be critical for developing combination therapies to help overcome checkpoint resistance. The potential of checkpoint therapies to amplify innate antitumor immunity represents a promising new field that can be translated into innovative immunotherapies for patients fighting refractory malignancies.

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 Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_7) ◽  
pp. vii59-vii67 ◽  
Author(s):  
Sophia C Weinmann ◽  
David S Pisetsky
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Treatment ◽  
Cell Repertoire ◽  
Autoantibody Production ◽  
Rheumatic Manifestations ◽  
Checkpoint Inhibitor Therapy

AbstractImmune checkpoint inhibitors are novel biologic agents to treat cancer by inhibiting the regulatory interactions that limit T cell cytotoxicity to tumours. Current agents target either CTLA-4 or the PD-1/PD-L1 axis. Because checkpoints may also regulate autoreactivity, immune checkpoint inhibitor therapy is complicated by side effects known as immune-related adverse events (irAEs). The aim of this article is to review the mechanisms of these events. irAEs can involve different tissues and include arthritis and other rheumatic manifestations. The frequency of irAEs is related to the checkpoint inhibited, with the combination of agents more toxic. Because of their severity, irAEs can limit therapy and require immunosuppressive treatment. The mechanisms leading to irAEs are likely similar to those promoting anti-tumour responses and involve expansion of the T cell repertoire; furthermore, immune checkpoint inhibitors can affect B cell responses and induce autoantibody production. Better understanding of the mechanisms of irAEs will be important to improve patient outcome as well as quality of life during treatment.

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.

856 Preliminary review of Diabetes Mellitus incidence in patients treated with immune checkpoint inhibitors (ICI) therapy – Roswell Park Comprehensive Cancer Center (RPCCC) experience

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A909-A909
Author(s):  
Zhen Zhang ◽  
Grazyna Riebandt ◽  
Rajeev Sharma ◽  
Lamya Hamad ◽  
Jordan Scott ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Diagnosed Diabetes ◽  
Newly Diagnosed Diabetes ◽  
New Onset

BackgroundImmune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment and has become a standard of care. There are now numerous FDA approved indications for ICIs and an increasing number of patients receiving these treatments, which has led to an increase in the risk of immune-related adverse events (irAEs) including endocrinopathies. Diabetes mellitus is a rare irAE of ICI therapy with an approximate incidence of 1-2%. There is paucity of data in literature about incidence, characteristics and possible predictive factors of ICI-induced diabetes mellitus. Due to limited data on ICI-induced diabetes, we conducted a retrospective review of patients who received ICI therapy at RPCCC and developed diabetes mellitus. The goal of this study is to report incidence and characteristics of new onset and worsening of diabetes in patients treated with ICI therapy.MethodsWe conducted a retrospective chart review of patients who received ICIs treatment from January 1st, 2010 to May 15th, 2020. We identified patients with newly diagnosed diabetes and worsening of preexisting diabetes. Newly diagnosed diabetes was defined as fasting blood glucose ≥ 126 or hemoglobin A1c (HbA1c) ≥ 6.5, random blood glucose ≥ 200 mg/dL with symptoms or 2-hour blood glucose ≥ 200 mg/dL on oral glucose tolerance test. Worsening of preexisting diabetes, defined as more than 0.5% increase in absolute HbA1c value in preceding 3-6 months or need for insulin in stable patients with diabetes on oral hypoglycemic agents. Subjects with pre-existing type 1 diabetes mellitus or on systemic corticosteroids for more than 1-week duration prior to diagnosis of diabetes mellitus were excluded.ResultsAmong 2,382 reviewed patients who received one or multiple ICIs, 15 patients developed new onset of diabetes and 12 patients experienced worsening of pre-existing Type 2 diabetes. In these 27 patients, 8 presented with diabetic ketoacidosis. Median time to new onset diabetes or worsening diabetes from ICI treatment initiation was 19 weeks, ranging from 2 to 320 weeks. Positive autoantibodies were found in 3 patients, among who 2 patients with positive Glutamic Acid Decarboxylase (GAD65) antibodies and one patient with positive insulin autoantibodies (IAA).ConclusionsThe incidence of new onset diabetes and worsening diabetes in patients treated with ICI therapy was 1.1%.Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center‘s Ethics Board, IRB ID STUDY00001278/BDR 129520.Consent exemptReferencesAzoury SC, Straughan DM, Shukla V. Immune checkpoint inhibitors for cancer therapy: clinical efficacy and safety. Curr Cancer Drug Targets 2015;15(6):452-462.Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the society for immunotherapy of cancer (SITC) toxicity management working group. J Immunother Cancer 2017;5(1):95.Akturk HK, Kahramangil D, Sarwal A, Hoffecker L, Murad MH, Michels AW. Immune checkpoint inhibitor-induced type 1 diabetes: a systematic review and meta-analysis. Diabet Med 2019;36(9):1075-1081.

Myasthenia gravis induced or exacerbated by immune checkpoint inhibitors: a rising concern

2021 ◽  
Vol 14 (8) ◽  
pp. e243764 ◽  
Author(s):  
Behnam Hajihossainlou ◽  
Alisa Vasileva ◽  
Sukesh Manthri ◽  
Kanishka Chakraborty
Keyword(s):  
Respiratory Failure ◽  
Myasthenia Gravis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Therapy Options ◽  
Severity Of The Disease ◽  
Cell Death Protein ◽  
New Onset

Immune checkpoint inhibitors can cause immune side effects, with myasthenia gravis (MG) being relatively rare. With this review, we present 66-year-old man with melanoma treated with pembrolizumab who developed MG. With immuno-oncology (IO) single agent usage, 42 cases reported new-onset MG and 9 cases reported exacerbation of pre-existing MG. Among the patients who had new-onset MG after administration of programmed cell death protein 1 (PD-1) inhibitors, 14 patients (38.8%) developed severe respiratory failure and required intubation and 10 patients (27.02%) died. Among the patients with exacerbation of pre-existing MG after receiving PD-1 inhibitors, 1 patient (11.1%) required intubation, and no death was reported. Combination IO therapy-induced MG was reported in seven cases, with at least two cases complicated by respiratory failure and one death. Our observations suggest a possible difference in the severity of the disease and outcome among different IO therapy options.

scholarly journals Diagnosis and Treatment of Rheumatic Adverse Events Related to Immune Checkpoint Inhibitors

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yan Xiao ◽  
Lin Zeng ◽  
Qinglin Shen ◽  
Zhiyong Zhou ◽  
Zhifang Mao ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Inflammatory Arthritis ◽  
Clinical Characteristics ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Inflammatory Myopathy ◽  
Treatment Strategies ◽  
Multiple Organ ◽  
Diagnosis And Treatment

Immune checkpoint inhibitors (ICIs) have completely changed the treatment of cancer, and they also can cause multiple organ immune-related adverse reactions (irAEs). Among them, rheumatic irAE is less common, mainly including inflammatory arthritis, rheumatic myalgia/giant cell arteritis, inflammatory myopathy, and Sjogren’s syndrome. For oncologists, rheumatism is a relatively new field, and early diagnosis and treatment is very important, and we need to work closely with experienced rheumatologists. In this review, we focused on the incidence, clinical characteristics, and treatment strategies of rheumatic irAE.

scholarly journals A HER2-Target Antibody Drug Conjugate Combined with anti-PD-(L)1 Treatment Eliminates hHER2 + Tumors in hPD-1 Transgenic Mouse Model and Contributes Immune Memory Formation

2021 ◽  
Author(s):  
Lei Huang ◽  
Ruiqin Wang ◽  
Kun Xie ◽  
jingming Zhang ◽  
Fei Tao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Memory Formation ◽  
Cancer Model ◽  
Antibody Drug Conjugate ◽  
Breast Cancer Model ◽  
Antibody Drug

Abstract Purpose: Disitamab vedotin (RC48) is an HER2-directed antibody-drug conjugate, emerging as an effective strategy for cancer therapy, not only enhance antitumor immunity in previous animal models but also improve clinical outcomes for patients such as with gastric cancer, urothelium carcinoma and HER2 low-expressing breast cancer. Here, we explore the combination therapeutic efficacy of this novel HER2-targeting ADC with immune checkpoint inhibitors in a human HER2-expressing syngeneic breast cancer model. Methods: The human HER2+ cancer cell line is constructed by stably transfection and individual clones were isolated by single-cell sorting. Flow cytometry was performed to determine its binding activity. Cytotoxic effect was determined using an MTT assay with the supplement of RC48. Human PD-1 transgenic mice were used to analyze the in vivo anti-tumor effects of the ADC and its combination therapy with PD-1/PD-L1 antibody. Results: The combination of RC48 and PD-1/PD-L1 immune checkpoint inhibition significantly enhanced tumor suppression and antitumor immunity. Tumor rejection in the synergistic groups was accompanied by massive T-cell infiltration and immune marker activation. Furthermore, the combination therapy promoted immunological memory formation in the tumor-eradication animals, protecting them from tumor rechallenge. Conclusion: A novel HER2-targeting ADC combined with immune checkpoint inhibitors can achieve remarkable effects in mice and elicit long-lasting immune protection in a hHER2+ murine breast cancer model. This study provides insights into the efficacy of RC48 therapeutic activity and a rationale for potential therapeutic combination strategies with immunotherapy.

Response of metastatic mucosal melanoma to immunotherapy: It can get worse before it gets better

2016 ◽  
Vol 23 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Shebli Atrash ◽  
Issam Makhoul ◽  
Jason S Mizell ◽  
Laura Hutchins ◽  
Fade Mahmoud
Keyword(s):  
Computed Tomography ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Mucosal Melanoma ◽  
Response To Treatment ◽  
Computed Tomography Scans ◽  
New Onset

Immune therapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. Ipilimumab, nivolumab, and pembrolizumab are all FDA-approved immune checkpoint inhibitors to treat metastatic melanoma. Responses to immune checkpoint inhibitors are usually delayed. An interim progression on restaging computed tomography scans “pseudo-progression” may be observed before response to treatment occur. In this case, we report a significant interim progression of metastatic mucosal melanoma before meaningful responses to immunotherapy occurred. The patient developed significant immune therapy-related colitis and new onset vitiligo. Further restaging computed tomography scans showed sustained tumor response despite stopping the immune therapy.

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