scholarly journals Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Barbara Barnes Rogers, CRNP, MN, AOCN, ANP-BC ◽  
Carolyn Zawislak, MPAS, PA-C ◽  
Victoria Wong, PA-C
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Blood Cells ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
White Blood Cells ◽  
Activated T Cells

Immune checkpoint inhibitors target suppressor receptors, including cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). The activated T cells are not antigen specific; therefore, the blockade of the immune checkpoint may result in the development of autoimmune adverse events. The most common immune-related adverse events (irAEs) are rash, colitis, and endocrinopathies. However, irAEs that affect the hematologic system are rare and can affect red blood cells (e.g., autoimmune hemolytic anemia), white blood cells, and platelets (e.g., immune thrombocytopenia). Usually one cell line is affected; however, in some cases, multiple cell lines can be affected. Other changes in the hematologic system can also be affected (e.g., cryoglobulinemia, cytokine release syndrome). Due to the rarity and lack of recognition of these AEs, the timing, spectrum of events, and clinical presentation are poorly understood. Management of hematologic irAEs usually involves the use of steroids; however, other agents (e.g., IVIG, cyclosporine, rituximab) or procedures (e.g., plasma exchange, transfusions) can also be used.

scholarly journals Toxicidade Cutânea dos Inibidores de Checkpoint Imunológico: Uma Revisão Narrativa

2020 ◽  
Vol 33 (5) ◽  
pp. 335
Author(s):  
Nuno Gomes ◽  
Vincent Sibaud ◽  
Filomena Azevedo ◽  
Sofia Magina
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Cutaneous Toxicity ◽  
Cell Death Protein

Introduction: Immune checkpoint inhibitors revolutionized anti-neoplastic treatment. Recently, the European Medicines Agency and the United States Food and Drug Administration approved inhibitors of various immune checkpoints, namely the cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and its ligand. Despite the added benefits in the treatment of several neoplasms, immune checkpoint blockade may also be associated with multiple immune-related adverse events.Material and Methods: A literature review in PubMed database on the cutaneous toxicity of immune checkpoint inhibitors was performed until April 30, 2019.Results and Discussion: A total of 380 articles were initially screened, of which 75 are the basis of this bibliographic review. The immune checkpoint inhibitors monoclonal antibodies produce their beneficial effects by activating the patient’s immune system. This activation also results in adverse events that can affect any organ, whereas cutaneous toxicity is the most frequent and precocious. The adverse events of the programmed cell death protein 1 and its ligand and of the cytotoxic T-lymphocyte-associated protein 4 are similar (class effect), despite the apparent higher skin toxicity of inhibitors of the cytotoxic T-lymphocyte-associated protein 4 (or its use in combination with inhibitors of programmed cell death protein 1 and its ligand). The most common cutaneous toxicities are maculopapular exanthema and pruritus, but other more specific adverse effects (e.g. lichenoid or psoriasiform reaction, vitiligo, sarcoidosis, among others) or located in the oral mucosa and/or adnexa are underreported.Conclusion: Given the high rate of cutaneous toxicity associated with new immune checkpoint inhibitors and their impact on quality of life, their early recognition and appropriate approach are crucial in the treatment of cancer patients. Observation by a dermatologist should be provided in patients with certain toxicities.

scholarly journals Anti–PD-L1 Treatment Induced Central Diabetes Insipidus

2017 ◽  
Vol 103 (2) ◽  
pp. 365-369 ◽  
Author(s):  
Chen Zhao ◽  
Sri Harsha Tella ◽  
Jaydira Del Rivero ◽  
Anuhya Kommalapati ◽  
Ifechukwude Ebenuwa ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Diabetes Insipidus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Central Diabetes Insipidus ◽  
Early Screening ◽  
Cell Death Protein

Abstract Context Immune checkpoint inhibitors, including anti–programmed cell death protein 1 (PD-1), anti–programmed cell death protein ligand 1 (PD-L1), and anti–cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti–CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade. Case Description We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti–PD-L1 monoclonal antibody avelumab and achieved partial response. The patient developed nocturia, polydipsia, and polyuria 3 months after starting avelumab. Further laboratory testing revealed central DI. Avelumab was held and he received desmopressin for the management of central DI. Within 6 weeks after discontinuation of avelumab, the patient’s symptoms resolved and he was eventually taken off desmopressin. The patient remained off avelumab and there were no signs or symptoms of DI 2 months after the discontinuation of desmopressin. Conclusion To our knowledge, this is the first report of central DI associated with anti–PD-L1 immunotherapy. The patient’s endocrinopathy was successfully managed by holding treatment with the immune checkpoint inhibitor. This case highlights the importance of early screening and appropriate management of hormonal irAEs in subjects undergoing treatment with immune checkpoint inhibitors to minimize morbidity and mortality.

scholarly journals Role of immune-checkpoint inhibitors in lung cancer

2018 ◽  
Vol 12 ◽  
pp. 175346581775007 ◽  
Author(s):  
Prantesh Jain ◽  
Chhavi Jain ◽  
Vamsidhar Velcheti
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Clinical Activity

Immune checkpoint inhibitors, mainly drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways, represent a remarkable advance in lung cancer treatment. Immune checkpoint inhibitors targeting PD-1 and PD-L1 are approved for the treatment of patients with non-small-cell lung cancer, with impressive clinical activity and durable responses in some patients. This review will summarize the mechanism of action of these drugs, the clinical development of these agents and the current role of these agents in the management of patients with lung cancer. In addition, the review will discuss the role of predictive biomarkers for optimal patient selection for immunotherapy and management of autoimmune side effects of these agents.

scholarly journals Immune checkpoint inhibitors for the treatment of glioblastoma: Where we are

2020 ◽  
Vol 10 (1) ◽  
pp. 7
Author(s):  
Bryan Lu ◽  
Senxi Du ◽  
Xiao-Tang Kong
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Human Cancer ◽  
Current Status ◽  
History Of

Despite a history of frequent challenges and roadblocks, there has been recent excitement in the treatment of human cancer, specifically regarding the remarkable efficacy of various immune checkpoint inhibitors including programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockers in treating metastatic melanoma, non-small cell lung cancer, and other malignant growths. However, treatment of glioblastoma multiforme (GBM) with immune checkpoint inhibitors so far has not been shown to be as successful in several randomized clinical trials as in other cancer with the exception of one pilot study that found promising results by neoadjuvant administration of Pembrolizimab for the treatment of recurrent GBM. Our article will review the current status of immune checkpoint inhibitors for the treatment of GBM.

scholarly journals Management of immune-related adverse events in patients treated with immune checkpoint inhibitors– Rheumatology point of view

2018 ◽  
Vol 18 (2) ◽  
pp. 56-60
Author(s):  
Cheuk Man Ho ◽  
Chi Chiu Mok
Keyword(s):  
Cell Death ◽  
Adverse Events ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Standard Treatment ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Point Of View ◽  
Cell Death Protein

Abstract The development of immunotherapy has revolutionized the cancer treatment in the recent years. Immune checkpoint inhibitors (ICPis) such as anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) and anti-programmed cell death protein (anti-PD1) and its ligand (anti-PDL1) have become part of the standard treatment of various malignancies. Immune-related adverse events (irAEs) were common in patients treated with ICPis. Rheumatologists should be aware of the upcoming challenges in the management of irAEs in a patient receiving treatment with ICPis.

284 Real World Data of Sequencing Immune Checkpoint Inhibitors (ICI) after Initial ICI

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A310-A310
Author(s):  
Krishna Gunturu ◽  
Muhammad Awidi ◽  
Rojer Ranjit ◽  
Brendan Connell ◽  
Rachel Carrasquillo ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Clear Understanding ◽  
Real World Data ◽  
World Data

BackgroundICI revolutionized modern Oncology landscape and being utilized in metastatic to adjuvant and neo-adjuvant settings. As Oncologists, we are treating cancer patients with ICI every day, yet there is still a lot that is unknown about these drugs. We don’t have clear understanding of the efficacy and toxicity when sequencing one ICI for another. We conducted a retrospective review of real world data at Lahey Hospital and Medical Center to understand further and to pave path for prospective studies to understand this issue further to improve patient care.MethodsWe retrospectively reviewed Oncology patient charts who received ICI between January1, 2014 to December 18, 2018. Total 483 patients received ICI during this time frame and 22 of these patients received a second ICI either as monotherapy or in combination with other ICI or chemotherapy.ResultsA total of 22 patients received subsequent ICI after the initial ICI as showed in table 1. 15 of the 22 (68%) patients were transitioned from one ICI to another monotherapy. 11 of these patients were transitioned secondary to disease progression (73%), three had immune related adverse events and one was switched per standard of care. One patient had ICI re-challenge. Three patients had a transition from ICI monotherapy to combination ICI therapy. One patient went onto chemo-immunotherapy and 2 patients transitioned from combination ICI to chemo-immunotherapy.Abstract 284 Table 1Real world data of sequencing immune checkpoint inhibitors (ICI) after initial ICIConclusionsICI therapy is evolving and patients are being treated with multiple lines of ICI. In current practices, ICI is frequently being transitioned from cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1) classes or combined with chemotherapy or targeted therapy. It would be prudent to explore the effects of sequencing these medications either as a monotherapy or in combination with other therapies to better serve our patients and to prevent financial toxicity.

Cancer Immunotherapy-Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

2021 ◽  
Vol 16 ◽  
Author(s):  
Jing Bai ◽  
Ping Liang ◽  
Qian Li ◽  
Rui Feng ◽  
Jiang Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Locoregional Therapy ◽  
Incidence And Mortality

: Hepatocellular Carcinoma (HCC) is one of the most common malignancies, the incidence and mortality of which are increasing worldwide. Cancer immunotherapy has revolutionized cancer treatment in recent years. In particular, Immune Checkpoint Inhibitors (ICIs) as new therapeutic tools have demonstrated encouraging antitumor activity and manageable tolerability in HCC. Immunologic checkpoint blockade with antibodies targeting Programmed cell Death-1 (PD-1), Programmed cell Death Ligand-1 (PD-L1), and Cytotoxic T Lymphocyte-Associated protein-4 (CTLA-4) strengthens tumor immunity by restoring exhausted T cells. Although the efficacy of combination treatment strategies using ICIs combined with other ICIs, molecular targeted agents, systemic therapy, or locoregional therapy has been well documented in numerous preclinical and clinical studies on several types of cancers, most HCC patients do not benefit from ICI treatment. This review highlights recent developments and potential opportunities related to ICIs and their combination in the management of HCC. The present article also includes recent patent review coverage on this topic.

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 Thrombocytopenia Induced by Immune Checkpoint Inhibitors in Solid Cancer: Case Report and Literature Review

2020 ◽  
Vol 10 ◽  
Author(s):  
Xiaolin Liu ◽  
Xiuju Liang ◽  
Jing Liang ◽  
Yan Li ◽  
Jun Wang
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Thrombocytopenia ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Case ◽  
Solid Cancer ◽  
Severe Thrombocytopenia ◽  
Advanced Cancer Patients

Immune checkpoint inhibitors, including antibodies targeting programmed cell death protein-1 (PD-1) and its receptor programmed cell death ligand-1 (PD-L1), represent promising therapeutic strategies for advanced human malignancies. However, a subgroup of patients experiences various autoimmune toxicities, termed immune-related adverse events (irAEs), that occur as a result of on-target and off-tumor autoimmune responses. Although irAEs are generally confirmed to be less severe than toxicities caused by conventional chemotherapy and targeted therapy, uncommon irAEs, such as immune thrombocytopenia, may occur with a very low incidence and sometimes be severe or fatal. This review focuses on the epidemiology, clinical presentation, and prognosis of immune thrombocytopenia occurring in advanced cancer patients induced by immune checkpoint inhibitors, especially in those with PD-1 or PD-L1 inhibitor treatment. We also first present one patient with non-small cell lung cancer who received the PD-L1 inhibitor durvalumab and developed severe thrombocytopenia.

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