Difficulties in differentiating between checkpoint inhibitor pneumonitis and lung metastasis in a patient with melanoma

Immunotherapy ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 293-298 ◽  
Author(s):  
Houssein Safa ◽  
Priya Bhosale ◽  
Annika Weissferdt ◽  
Isabella C Glitza Oliva
Keyword(s):  
Clinical Presentation ◽  
Cytotoxic T Lymphocyte ◽  
Late Onset ◽  
Checkpoint Inhibitors ◽  
Lung Nodule ◽  
Complete Response ◽  
Lung Lesions ◽  
Discontinuation Of Treatment ◽  
Cell Death Protein ◽  
New Onset

The use of immune checkpoint inhibitors is associated with significant toxicities such as pneumonitis; the clinical presentation of the latter can be misleading and may mimic metastasis. We report the case of a melanoma patient who developed late-onset pneumonitis after discontinuation of treatment with anti-programmed cell death protein 1 (PD1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) (patient had a complete response). The patient was asymptomatic, however, surveillance computed tomography (CT) scan showed a growing lung nodule and several new-onset, small lung lesions highly suspicious for recurrence. A biopsy of the lesions revealed organizing pneumonia with absence of malignant cells. The lung lesions completely resolved after 6 months without any intervention. The patient is still in complete remission 2 years after the initial diagnosis of melanoma.

Ipilimumab and nivolumab induced immune-related adverse events in metastatic mucosal melanoma

2021 ◽  
Vol 14 (8) ◽  
pp. e243713
Author(s):  
Yenong Cao ◽  
Muhammad Zubair Afzal ◽  
Keisuke Shirai
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Type I Diabetes ◽  
Complete Response ◽  
Mucosal Melanoma ◽  
Type I ◽  
Melanoma Treatment ◽  
Cell Death Protein

Mucosal melanoma is a rare subtype of melanoma and represents a unique diagnosis and treatment challenge. Immune-checkpoint inhibitors (ICIs) have revolutionised metastatic melanoma treatment, and one of the leading regimens is the combination of ipilimumab (anti-cytotoxic T lymphocyte-associated antigen 4: CTLA4) and nivolumab (anti-programmed cell death protein 1: PD1). We report a case of a patient with metastatic mucosal melanoma treated with ipilimumab and nivolumab who developed multiple immune-related adverse events (irAEs) including uveitis, type I diabetes complicated by diabetic ketoacidosis, destructive thyroiditis, hepatitis and vitiligo. Endocrinopathies including type 1 diabetes and hypothyroidism were treated with insulin and levothyroxine. Hepatitis was responsive to steroids. She had sustained complete response 12 months after discontinuation of the combination therapy. With the wide usage of ICIs in multiple types of malignancies, it is important for general practioners to recognise common and serious irAEs due to ICIs.

scholarly journals Rheumatic immune-related adverse events from checkpoint inhibitor therapy: a case series

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Antonella Laria ◽  
Alfredomaria Lurati ◽  
Laura Castelnovo ◽  
Antonio Tamburello ◽  
Paola Maria Faggioli ◽  
...  
Keyword(s):  
Adverse Events ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Hematologic Malignancies ◽  
Checkpoint Inhibitor Therapy ◽  
Cancer Immunotherapies ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and its ligand PD-L1 are established cancer immunotherapies for solid tumor and hematologic malignancies. These therapies are involved in immune-related adverse events (irAE), both general and rheumatic ones. In general, immune-related adverse events (irAE) management includes drug-holding, tapering doses of corticosteroids, and specific immunosuppression for clinically severe cases, such as infliximab or mycophenolate.

scholarly journals Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Wang Xie ◽  
NaNa Hu ◽  
LeJie Cao
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Clinical Presentation ◽  
Checkpoint Inhibitors ◽  
Immune Dysregulation ◽  
Cancer Case ◽  
Severe Thrombocytopenia ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs), including antibodies targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1), are being extensively used on advanced human malignancies therapy. The treatment with ICIs have acquired durable tumor inhibition and changed the treatment landscape in lung cancer. Immune-related adverse events including pneumonitis and thyroiditis have been well described, but less frequent events, such as ICIs-induced thrombocytopenia, are now emerging and may sometimes be severe or fatal. Since early detection and prompt intervention are crucial to prevent fatal consequences, it is of outmost importance that medical staff is aware of these potential toxicities and learn to recognize and treat them adequately. This review focuses on the epidemiology, clinical presentation, mechanisms, and clinical management of ICIs-induced thrombocytopenia in patients with lung cancer. We also present a patient with advanced lung adenocarcinoma who received the PD-L1 inhibitor atezolizumab and eventually developed severe thrombocytopenia. The case indirectly suggests that cytokine changes might contribute to immune dysregulation in ICIs-induced thrombocytopenia.

Autoimmune complications of immunotherapy: pathophysiology and management

BMJ ◽  
2020 ◽  
pp. m736 ◽  
Author(s):  
Karmela K Chan ◽  
Anne R Bass
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Case Fatality ◽  
High Grade ◽  
Almost All ◽  
Inhibitory Molecules ◽  
Patients Experience ◽  
Cell Death Protein

Abstract Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1), and lead to immune activation in the tumor micro-environment. ICIs can induce durable treatment responses in patients with advanced cancers, but they are commonly associated with immune related adverse events (irAEs) such as rash, colitis, hepatitis, pneumonitis, and endocrine and musculoskeletal disorders. Almost all patients experience some form of irAE, but high grade irAEs occur in approximately half of those on combination therapy (eg, anti-CTLA-4 plus anti-PD-1), and up to one quarter receiving ICI monotherapy. Fatal irAEs occur in approximately 1.2% of patients on CTLA-4 blockade and 0.4% of patients receiving PD-1 or PD-L1 blockade, and case fatality rates are highest for myocarditis and myositis. IrAEs typically occur in the first three months after ICI initiation, but can occur as early as one day after the first dose to years after ICI initiation. The mainstay of treatment is with corticosteroids, but tumor necrosis factor inhibitors are commonly used for refractory irAEs. Although ICIs are generally discontinued when high grade irAEs occur, ICI discontinuation alone is rarely adequate to resolve irAEs. Consensus guidelines have been published to help guide management, but will likely be modified as our understanding of irAEs grows.

Synergies of Targeting Angiogenesis and Immune Checkpoints in Cancer: From Mechanism to Clinical Applications

2020 ◽  
Vol 20 (7) ◽  
pp. 768-776 ◽  
Author(s):  
Shi Zhou ◽  
Haijun Zhang
Keyword(s):  
Web Of Science ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Angiogenesis Inhibitors ◽  
Immune Checkpoints ◽  
Antiangiogenic Agents ◽  
Recent Developments ◽  
Antiangiogenic Drugs ◽  
Tumor Types ◽  
Cell Death Protein

Background: Angiogenesis marks key progress in the growth, recurrence, and metastasis of various cancers. Antiangiogenic drugs can improve the blood supply and oxygen content of tumors and enhance the effects of chemotherapy and radiotherapy by normalizing tumor blood vessels and microenvironment. The further recent developments of Immune Checkpoint Inhibitors (ICIs) provide significant progress in cancer immunotherapy. The study focused on programmed cell death protein 1 (PD-1) and Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) blockade, reflecting on the evidence of durable responses among various tumor types. The aim of this review was to sum up present evidence and clarify the rationale behind supporting the benefits of combining antiangiogenic drugs with immunotherapy for cancer treatment as well as list the ongoing clinical trials that are being conducted. Methods: Using PubMed and Web of Science, published articles have been searched and comprehensively reviewed. Results: Antiangiogenic agents can trigger antitumor and immunity, and they can also be induced by the immune system. Combining antiangiogenic drugs with immunotherapy may be effective for the treatment of human cancers. Conclusion: It is evidenced that combining angiogenesis inhibitors with immunotherapy has a synergistic effect thus improving the curative effect of both agents.

scholarly journals The Central Role of Inflammation Associated with Checkpoint Inhibitor Treatments

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Cristina Vajaitu ◽  
Carmen Cristina Draghici ◽  
Iulia Solomon ◽  
Cristina Victoria Lisievici ◽  
Alexandra Victoria Popa ◽  
...  
Keyword(s):  
Response Rate ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Overall Survival Rate ◽  
Small Cell Lung ◽  
Cancer And Inflammation ◽  
Cell Death Protein ◽  
Free Rate

An important function of the immune system is its ability to differentiate between healthy cells in the organism and “foreign” cells, allowing the latest to be attacked and the first ones to be conserved. The most important molecules in this process are considered to be checkpoint inhibitors. This review is focused on the association between cancer and inflammation, underlying the mechanisms of action of monoclonal antibodies that are targeting checkpoint inhibitors: ipilimumab against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and pembrolizumab and nivolumab against programmed cell death protein 1 (PD-1), their indications for treatment, and side effects. Presence of antibodies against checkpoint inhibitors shows promising results in the clinical trials in patients with types of cancer difficult to treat until now such as melanoma, non-small-cell lung cancer (NSCLC), and renal cell carcinoma, offering an increase in the overall survival rate, response rate, and progression-free rate. Resistance is now observed to emerge in patients treated with this therapy, showing the need for more studies in order to design a biomarker that will predict the type of response to immunotherapy.

scholarly journals Combination of Ipilimumab and Nivolumab in Cancers: From Clinical Practice to Ongoing Clinical Trials

2020 ◽  
Vol 21 (12) ◽  
pp. 4427 ◽  
Author(s):  
Omid Kooshkaki ◽  
Afshin Derakhshani ◽  
Negar Hosseinkhani ◽  
Mitra Torabi ◽  
Sahar Safaei ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Combination Therapy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Clinical Activity ◽  
Efficacy And Safety ◽  
Activated T Cells ◽  
Oncological Outcomes ◽  
Cell Death Protein

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are inhibitory checkpoints that are commonly seen on activated T cells and have been offered as promising targets for the treatment of cancers. Immune checkpoint inhibitors (ICIs)targeting PD-1, including pembrolizumab and nivolumab, and those targeting its ligand PD-L1, including avelumab, atezolizumab, and durvalumab, and two drugs targeting CTLA-4, including ipilimumab and tremelimumab have been approved for the treatment of several cancers and many others are under investigating in advanced trial phases. ICIs increased antitumor T cells’ responses and showed a key role in reducing the acquired immune system tolerance which is overexpressed by cancer and tumor microenvironment. However, 50% of patients could not benefit from ICIs monotherapy. To overcome this, a combination of ipilimumab and nivolumab is frequently investigated as an approach to improve oncological outcomes. Despite promising results for the combination of ipilimumab and nivolumab, safety concerns slowed down the development of such strategies. Herein, we review data concerning the clinical activity and the adverse events of ipilimumab and nivolumab combination therapy, assessing ongoing clinical trials to identify clinical outlines that may support combination therapy as an effective treatment. To the best of our knowledge, this paper is one of the first studies to evaluate the efficacy and safety of ipilimumab and nivolumab combination therapy in several cancers.

Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective

2018 ◽  
Vol 71 (8) ◽  
pp. 665-671 ◽  
Author(s):  
Dipti M Karamchandani ◽  
Runjan Chetty
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Immune Mediated ◽  
Self Tolerance ◽  
Novel Drugs ◽  
Cell Death Protein

Immune checkpoint inhibitors (CPIs) are a relatively new class of ‘miracle’ dugs that have revolutionised the treatment and prognosis of some advanced-stage malignancies, and have increased the survival rates significantly. This class of drugs includes cytotoxic T lymphocyte antigen-4 inhibitors such as ipilimumab; programmed cell death protein-1 inhibitors such as nivolumab, pembrolizumab and avelumab; and programmed cell death protein ligand-1 inhibitors such as atezolizumab. These drugs stimulate the immune system by blocking the coinhibitory receptors on the T cells and lead to antitumoural response. However, a flip side of these novel drugs is immune-related adverse events (irAEs), secondary to immune-mediated process due to disrupted self-tolerance. The irAEs in the gastrointestinal (GI) tract/liver may result in diarrhoea, colitis or hepatitis. An accurate diagnosis of CPI-induced colitis and/or hepatitis is essential for optimal patient management. As we anticipate greater use of these drugs in the future given the significant clinical response, pathologists need to be aware of the spectrum of histological findings that may be encountered in GI and/or liver biopsies received from these patients, as well as differentiate them from its histopathological mimics. This present review discusses the clinical features, detailed histopathological features, management and the differential diagnosis of the luminal GI and hepatic irAEs that may be encountered secondary to CPI therapy.

scholarly journals Overview and management of toxicities of immune checkpoint-blocking drugs

2016 ◽  
Vol 7 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Panagiota Economopoulou ◽  
Amanda Psyrri
Keyword(s):  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Cancer Management ◽  
New Methods ◽  
Organ Specific ◽  
Clinical Benefits ◽  
Immune Oncology ◽  
Cell Death Protein

Abstract Immunotherapy is considered to be the most important breakthrough in cancer management in the past few years. This success was based on the scientific understanding of immune mechanisms due to improvement in preclinical science and the introduction of new methods of investigation. Immune checkpoint inhibitors (ICIs) are among the most promising drugs in the field of immune-oncology; they represent monoclonal antibodies that modulate the effects of immune checkpoints, such as cytotoxic T lymphocyte Antigen 4 (CTLA-4) and Programmed Cell Death protein 1 (PD-1), which are co-inhibitory signals responsible for immune suppression. Despite clinical benefits, ICIs are immune activating agents that are associated with a number of important side effects (immune-related adverse events-irAEs), attributed to organ-specific inflammation. Herein, we review the toxicities of ICIs, highlighting the importance of early identification and management.

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.

Sign in / Sign up

Export Citation Format

Share Document