scholarly journals Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort

2016 ◽  
Vol 74 (3) ◽  
pp. 455-461.e1 ◽  
Author(s):  
Shelley Ji Eun Hwang ◽  
Giuliana Carlos ◽  
Deepal Wakade ◽  
Karen Byth ◽  
Benjamin Y. Kong ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Single Institution

Safe anti-programmed cell death-1 rechallenge with antibody switching after immune-related adverse events: brief communication

Immunotherapy ◽  
2021 ◽  
Author(s):  
Francisco Aya ◽  
E Azucena González-Navarro ◽  
Clara Martínez ◽  
Esther Carcelero ◽  
Ana Arance
Keyword(s):  
Cell Death ◽  
Adverse Event ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Related Adverse Event ◽  
Safe Strategy ◽  
Programmed Cell Death 1 ◽  
Safety Outcomes ◽  
Biological Differences

Aim: To evaluate the safety of rechallenge with a different anti-PD-1 antibody after an immune-related adverse event (irAE) that has prompted the discontinuation of anti-PD-1 therapy. Patients & methods: We describe two patients with metastatic melanoma who developed potentially disabling and early irAEs following anti-PD-1 treatment. Therapy was discontinued and toxicities resolved with corticosteroids. Results: Rechallenge switching to an alternative anti-PD-1 antibody did not lead to a new or recurrent irAE. Conclusion: Switching to a different anti-PD-1 antibody when resuming therapy after an irAE might be a safe strategy and warrants further investigation. Structural and biological differences between antibodies might explain the different safety outcomes.

scholarly journals Association of Antibiotics and Other Drugs with Clinical Outcomes in Metastatic Melanoma Patients Treated with Immunotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Manish D. Angrish ◽  
Arun Agha ◽  
Rossanna C. Pezo
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Secondary Outcome ◽  
Lung Cancers ◽  
Gut Dysbiosis ◽  
Negative Effect ◽  
Melanoma Patients

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have improved survival in many advanced cancers including advanced melanoma, renal cell, urothelial, and non-small-cell lung cancers. However, not all patients respond, and immune-related adverse events (irAEs) are common. Commensal gut bacteria may serve as an immunoregulatory link-mediating ICI response and toxicity. Recent studies have shown that a lack of bacterial diversity, known as gut dysbiosis, can have an adverse impact on patients’ response to ICIs and predispose to the development of irAEs. Data were collected from 167 patients with metastatic melanoma who received antibiotics within 30 days prior to and/or after initiation of ICI and patients who received NSAIDs, statins, steroids, or proton-pump inhibitors (PPI) within 30 days prior to ICI initiation. The primary outcome was time-to-discontinuation (TTD) of ICI therapy, measured from the date of ICI initiation to the last treatment date. The secondary outcome of interest was toxicity, with incidence of irAEs graded as per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Here, we demonstrate that individuals who received antibiotics had a significantly shorter time-to-discontinuation (TTD) of the ICI therapy as opposed those who were not administered antibiotics. Consistent with results from previous research, we propose that antibiotics have a negative effect on a patient’s response to ICI therapy, most likely due to the result of gut dysbiosis, and should be critically assessed in terms of their use in patients undergoing ICI treatment.

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient?

2021 ◽  
pp. 107815522110381
Author(s):  
Esra Özyurt ◽  
Serhat Özçelik ◽  
Heves Sürmeli ◽  
Mehmet Çelik ◽  
Murat Ayhan ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Side Effects ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immunoglobulin G4 ◽  
Programmed Cell Death 1 ◽  
Recurrent Renal Cell Carcinoma

Introduction Nivolumab is a human immunoglobulin G4 monoclonal antibody that inhibits programmed cell death-1 activity by binding to the programmed cell death-1 receptors. Cancer cells express increased number of programmed cell death-1 ligands and this allows them to escape the cytotoxic effects of the T cells. Therefore, the negative programmed cell death-1 receptor signal regulates T-cell proliferation and activation is disrupted. However, this change in the activity of the T cells can cause them to lose their ability to recognize host cells. The immune response enabled by these agents has led to side effects, commonly known as “immune-related adverse events.” Case report We report a case of a 66-year-old male patient who was treated with nivolumab for recurrent renal cell carcinoma presented with hepatitis and adrenalitis. Three weeks after starting nivolumab, the patient had abdominal pain and weakness, and then aspartate and alanine transaminase levels were found to be elevated. Management and outcome Hepatitis was predicted to be due to nivolumab, because other causes were excluded. He started using oral methylprednisolone and then, hepatitis improved. However, while receiving methylprednisolone treatment, fludrocortisone was started with the pre-diagnosis of adrenalitis due to the persistence of fatigue, weakness, and hyponatremia and hyperkalemia. With both treatments, the patient's symptoms and sodium and potassium level returned to normal. Discussion This case emphasizes the need for patient's education and awareness of immune-related adverse events, and the importance of understanding the management of life-threatening complications of the checkpoint inhibitors, because these side effects require prompt recognition and treatment.

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 Programmed cell death-1 and programmed cell death ligand-1 antibodies-induced dysthyroidism

2018 ◽  
Vol 7 (5) ◽  
pp. R196-R211 ◽  
Author(s):  
Jaafar Jaafar ◽  
Eugenio Fernandez ◽  
Heba Alwan ◽  
Jacques Philippe
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
English Language ◽  
Case Series ◽  
Immune Checkpoints ◽  
Pubmed Database ◽  
Programmed Cell Death 1 ◽  
Time To Onset

Background Monoclonal antibodies blocking the programmed cell death-1 (PD-1) or its ligand (PD-L1) are a group of immune checkpoints inhibitors (ICIs) with proven antitumor efficacy. However, their use is complicated by immune-related adverse events (irAEs), including endocrine adverse events (eAEs). Purpose We review the incidence, time to onset and resolution rate of dysthyroidism induced by PD-1/PD-L1 Ab, and the clinical, biological and radiological findings. We aim to discuss the potential mechanisms of PD-1/PD-L1 Ab-induced dysthyroidism, and to propose a management algorithm. Methods We performed a literature search of available clinical trials regarding PD-1/PD-L1 Ab in the PubMed database. We selected all English language clinical trials that included at least 100 patients. We also present selected case series or reports, retrospective studies and reviews related to this issue. Findings In patients treated with PD-1 Ab, hypothyroidism occurred in 2–10.1% and hyperthyroidism occurred in 0.9–7.8%. When thyroiditis was reported separately, it occurred in 0.34–2.6%. Higher rates were reported when PD-1 Ab were associated with other ICI or chemotherapy. The median time to onset of hyperthyroidism and hypothyroidism after PD-1 Ab initiation was 23–45 days and 2–3.5 months, respectively. Regarding PD-L1 Ab, hypothyroidism occurred in 0–10% and hyperthyroidism in 0.5–2% of treated patients. The average time to onset of dysthyroidism after PD-L1 Ab was variable and ranged from 1 day after treatment initiation to 31 months. Conclusion Dysthyroidism occurs in up to 10% of patients treated with PD-1/PD-L1 Ab. Hypothyroidism and reversible destructive thyroiditis are the most frequent endocrine adverse events (eAE) in PD-1/PD-L1 treated patients. Immune and non-immune mechanisms are potentially involved, independently of the presence of thyroid antibodies.

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