scholarly journals Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Koji Yoshino ◽  
Takayuki Nakayama ◽  
Ayumu Ito ◽  
Eiichi Sato ◽  
Shigehisa Kitano
Keyword(s):  
Adverse Events ◽  
Case Reports ◽  
Pathological Examination ◽  
Dominant Response ◽  
Reactive Protein ◽  
Programmed Death ◽  
Potential Biomarker ◽  
Clinical Responses ◽  
Programmed Death 1

Abstract Background Nivolumab is an immune checkpoint inhibitor specific to the programmed death 1 (PD-1) receptor. Nivolumab has shown clinical responses in many malignancies. Although immune-related adverse events (irAEs) associated with nivolumab are largely tolerable, severe irAEs have occurred in some patients. However, the mechanisms underlying the development of irAEs are not fully clarified. Case presentation We report 2 patients with metastatic melanoma who developed colitis, an irAEs caused by nivolumab. Both patients experienced colitis after nivolumab administration. Pathological examination of the colon showed robust infiltration of CD8+ cells and T-bet expressing CD4+ cells in both cases, indicating helper T cells (Th) 1 to be responsible for the dominant response. Additionally, we observed the serum C-reactive protein level (CRP) as well as interleukin-6 (IL-6) reflected the clinical course of irAEs clearly in the two cases. Conclusion Our two cases suggested that the development of irAEs due to nivolumab is associated with Th1 dominant response. CRP as well as IL-6 was found to be a potential biomarker for irAEs. Our findings may help to understand the mechanisms underlying irAEs caused by nivolumab and manage irAEs in clinical practice.

scholarly journals Protective Role of Programmed Death 1 Ligand 1 (PD-L1)in Nonobese Diabetic Mice: The Paradox in Transgenic Models

Diabetes ◽  
2008 ◽  
Vol 57 (7) ◽  
pp. 1861-1869 ◽  
Author(s):  
C.-J. Wang ◽  
F.-C. Chou ◽  
C.-H. Chu ◽  
J.-C. Wu ◽  
S.-H. Lin ◽  
...  
Keyword(s):  
Protective Role ◽  
Diabetic Mice ◽  
Transgenic Models ◽  
Nonobese Diabetic ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Nonobese Diabetic Mice

Gastrointestinal Immune Related Adverse Events Associated with Programmed-Death 1 Blockade

2017 ◽  
Vol 152 (5) ◽  
pp. S194
Author(s):  
Michael Collins ◽  
Jean-Marie Michot ◽  
François-Xavier Danlos ◽  
Stéphane Champiat ◽  
Charlotte Mussini ◽  
...  
Keyword(s):  
Adverse Events ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Management of Adverse Events Following Treatment With Anti‐Programmed Death‐1 Agents

2016 ◽  
Vol 21 (10) ◽  
pp. 1230-1240 ◽  
Author(s):  
Jeffrey S. Weber ◽  
Michael Postow ◽  
Christopher D. Lao ◽  
Dirk Schadendorf
Keyword(s):  
Adverse Events ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals A case report of psoriasis flare following immunotherapy: Report of an important entity and literature review

2020 ◽  
Vol 8 ◽  
pp. 2050313X1989770 ◽  
Author(s):  
Anastasia Politi ◽  
Dimas Angelos ◽  
Davide Mauri ◽  
George Zarkavelis ◽  
George Pentheroudakis
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Skin Lesions ◽  
Inflammatory Disorder ◽  
Immune Mediated ◽  
Programmed Death ◽  
History Of ◽  
Programmed Death 1 ◽  
Cessation Of Treatment

Immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed death-1, are a type of cancer immunotherapy approved for late-stage malignancy treatment. However, such therapies often induce immune-related adverse events. During anti-programmed death-1 blockade therapy, the most commonly reported adverse effects are skin toxicities, such as psoriasis—a chronic immune-mediated inflammatory disorder affecting the skin. We present the clinical characteristics of flared psoriasis in one patient under anti-programmed death-1 therapy who was diagnosed with T2N2M0/IIIB squamous lung carcinoma with a history of psoriasis for the past 5 years, exacerbated after the first cycle of nivolumab. After the third cycle, the extensive skin plaques necessitated treatment cessation. Following the discontinuation of anti-programmed death-1 treatment, skin lesions were treated locally. Possibly, anti-programmed death-1 immunotherapy can trigger immune-mediated diseases, such as psoriasis. Physicians should be alert to immune-related adverse events. Continuation or permanent cessation of treatment depends on the severity and reversibility of immune-related adverse events.

scholarly journals Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma

2018 ◽  
Vol 36 (10) ◽  
pp. 942-950 ◽  
Author(s):  
Margaretha G.M. Roemer ◽  
Robert A. Redd ◽  
Fathima Zumla Cader ◽  
Christine J. Pak ◽  
Sara Abdelrahman ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Histocompatibility Complex ◽  
Classic Hodgkin Lymphoma ◽  
Programmed Death ◽  
Clinical Responses ◽  
Programmed Death 1 ◽  
Cell Expression

Purpose Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/ CD274(PD-L1)/ PDCD1LG2(PD-L2) and perturbed antigen presentation. Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells. Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti–PD-1) in the CheckMate 205 trial. Methods HRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components—β2-microglobulin, MHC class I, and MHC class II—by immunohistochemistry. These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade. Results Patients with higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells had superior PFS. HRS cell expression of β2-microglobulin/MHC class I was not predictive for complete remission or PFS after nivolumab therapy. In contrast, HRS cell expression of MHC class II was predictive for complete remission. In patients with a > 12-month interval between myeloablative autologous stem-cell transplantation and nivolumab therapy, HRS cell expression of MHC class II was associated with prolonged PFS. Conclusion Genetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In cHL, clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I.

scholarly journals Acute kidney injury from immune checkpoint inhibitor use

2019 ◽  
Vol 12 (10) ◽  
pp. e231211 ◽  
Author(s):  
Lexis Gordon ◽  
Pouneh Dokouhaki ◽  
Kimberly Hagel ◽  
Bhanu Prasad
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Programmed Death ◽  
Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

scholarly journals Total Ankle Replacement in Hemophilia

2020 ◽  
Vol 20 (2) ◽  
pp. 88-92
Author(s):  
Emerito C. Rodriguez-Merchan
Keyword(s):  
Adverse Events ◽  
Daily Living ◽  
Case Reports ◽  
Case Series ◽  
Total Ankle Replacement ◽  
Cochrane Library ◽  
Hemophilic Arthropathy ◽  
Accessible Information ◽  
Ankle Replacement

Introduction: Severe ankle hemophilic arthropathy can be a calamitous sign of severe hemophilia with important inferences for activities of daily living. Aims: To summarize the contemporary, accessible information on Total Ankle Replacement (TAR) for ankle hemophilic arthropathy. Methods: A search of Cochrane Library and PubMed (MEDLINE) regarding the role of TAR in ankle hemophilic arthropathy. Results: The insufficient information regarding the results of TAR for hemophilic arthropathy is confined to scanty case series and case reports. An evaluation of the accessible literature reveals encouraging but inconstant outcomes. The reported rate of adverse events is 33%. The reported anticipated survival of TAR is 94% at 5 years, 85% at 10 years and 70% at 15 years. Conclusion: Whereas people with advanced hemophilic arthropathy of the ankle are prone to ameliorate pain and range of motion following TAR, there is deficient knowledge to regularly recommend its use. Adverse events and infection percentages are disturbing. Moreover, the lack of survival analysis knowledge makes it difficult to assess the benefit to people with hemophilia. TAR is a demanding surgical procedure and its survival is not comparable to that after hip or knee replacement.

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