scholarly journals Pembrolizumab-Induced Immune-Mediated Colitis in a Patient with Concurrent Clostridium Difficile Infection

2019 ◽  
Vol 12 (1) ◽  
pp. 164-170 ◽  
Author(s):  
Cheng Zhou ◽  
Yael Klionsky ◽  
Michelle E. Treasure ◽  
Debora S. Bruno
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Appropriate Treatment ◽  
Immune Mediated ◽  
Programmed Death ◽  
Timely Fashion ◽  
Infectious Etiology ◽  
Severe Colitis

Pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor that has been approved for treatment of a wide variety of malignancies. Immune-mediated colitis is a known but uncommon adverse effect of pembrolizumab. Symptoms of immune-mediated colitis can be similar to those of many other gastrointestinal illnesses, including Clostridium difficile infection (CDI). If not recognized and treated in a timely fashion, immune-mediated colitis can lead to significant morbidity in cancer patients. We report the case of a 56-year-old woman on pembrolizumab for metastatic non-small cell lung cancer (NSCLC) who presented with severe colitis symptoms and initially tested positive for CDI. Her colitis symptoms worsened despite appropriate treatment for CDI but later improved rapidly after systemic corticosteroid was started for suspected immune-mediated colitis. To our knowledge, this is the first reported case of concurrent pembrolizumab-induced colitis and CDI. Immune-mediated colitis should be considered in the differential diagnoses in patients on pembrolizumab or other immune checkpoint inhibitors who present with colitis symptoms, even when a concurrent infectious etiology is suspected.

scholarly journals Immune-Related Pancytopenia Induced by Anti-PD-1 Therapy – Interrupt or Continue Treatment – The Role of Immunohistochemical Examination

2019 ◽  
Vol 12 (3) ◽  
pp. 820-828 ◽  
Author(s):  
Bożena Cybulska-Stopa ◽  
Andrzej Gruchała ◽  
Maciej Niemiec
Keyword(s):  
Bone Marrow ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Positive Outcomes ◽  
Hematological Disorders ◽  
Therapeutic Outcomes ◽  
Appropriate Treatment ◽  
Programmed Death

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed death receptor-1/ligand-1 (anti-PD-1/anti-PD-L1) caused a breakthrough in oncology and significantly improved therapeutic outcomes in cancer patients. ICIs generate a specific reaction in T cells, directed against antigens on cancer cells, leading to their damage and death. Through similar or the same antigens, activated lymphocytes may also have a cytotoxic effect on healthy cells, causing development of specific adverse effects – so-called immune-related adverse events (irAEs). We present the case report of a 56 year old patient with disseminated melanoma. During treatment with immunotherapy (anti PD-1), neutropenic fever and pancytopenia occurred. Trepanobiopsy of the bone marrow was performed to determine the cause of pancytopenia. Histopathological assessment of bone marrow combined with immunophenotype investigations may explain the cause of hematological disorders occurring in the course of treatment with ICIs, and support the choice of an appropriate treatment, directly translated into positive outcomes.

Behcet’s-like syndrome following pembrolizumab: An immune-related adverse event associated with programmed death receptor-1 inhibitor therapy

2019 ◽  
Vol 26 (4) ◽  
pp. 995-999 ◽  
Author(s):  
Steffi Thomas ◽  
Chay Bae ◽  
Tabanor Joy-Ann ◽  
William Traverse
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Programmed Death ◽  
Organ Systems ◽  
Wide Range ◽  
The Right

Introduction The landscape for the treatment of metastatic melanoma has been revolutionized with the introduction immune checkpoint inhibitors. Immune checkpoint inhibitors have now become the standard of care for the treatment of cancers. These immune agents including programmed death receptor-1 inhibitors, programmed death-ligand 1 inhibitors and cytotoxic T-lymphocyte antigen-4 inhibitors have shown promising results but have been associated with numerous immune-related complications. Pembrolizumab, a programmed death receptor-1 inhibitor, has been associated with a number of immune-related adverse events affecting multiple organ systems including integument, ocular, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal system. Case report We present a case of an 88-year-old Caucasian male with metastatic melanoma of the face with metastasis to the right fifth cranial nerve and into the right cavernous sinus. He underwent resection of the melanoma and was placed on pembrolizumab at 2 mg/kg every three weeks. Interestingly, 24 months on pembrolizumab therapy, he developed corneal erosions, oral and genital ulcerations. Management and outcome Patient completed his 24 months of pembrolizumab and was started on prednisone and colchicine with improvement in his symptoms. At his follow-up eight months, he had recurrence of an oral ulcer. Discussion Here we present a rare case of an elderly male on pembrolizumab who suffered from corneal erosions, oral and genital ulcers, a syndrome similar to Behcet’s disease. Given that pembrolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the wide range immune-related adverse events including the possible Behcet’s-like syndrome presentation.

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 Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings

2021 ◽  
Vol 2 ◽  
Author(s):  
Alex Dobriyan ◽  
Iris Gluck ◽  
Eran Alon ◽  
Iris Barshack ◽  
Ran Yahalom ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
T Regulatory Cells ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Complete Response ◽  
The Other ◽  
Initial Stage ◽  
Programmed Death ◽  
Number Of Patients ◽  
Bony Involvement

Background: The tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is associated with immune suppression, one of the pathways being the programmed death receptor 1 (PD-1) and its ligands (PD-L1/PD-L2). Checkpoint inhibitors of PD-1/PD-L1, like pembrolizumab, have been recently approved for treatment of OSCC. We described the histologic findings in OSCC following neoadjuvant pembrolizumab, including identification of immune-related cell populations and cancer-associated fibroblasts (CAFs).Materials and Methods: Patients with OSCC clinical stages 3 and 4 and a combined PD-L1 score >1 were randomized either to the standard oncologic protocol or to the pembrolizumab arm of MK-3475-689 study for Head and Neck, Lip, and Oral Cavity. The latter were given two standard doses of 200 mg of pembrolizumab, 3 weeks apart, and then underwent surgical oncologic procedure according to the initial stage. Sections from the resection specimens were analyzed for pathological response to pembrolizumab. Various populations of immune-related cells within the tumor microenvironment were characterized by immunohistochemistry, as were the CAFs.Results: Three patients who were randomized to the pembrolizumab study were described. One patient presented with a tongue SCC, the other two had SCC of the mandibular ridge with bony involvement. Only the patient with tongue SCC showed clinical complete response. Microscopically, the tumor was replaced by a granulomatous type of inflammation. Immunohistochemical stains revealed massive T cell rich (CD3+) infiltrate, with approximately equal amounts of CD4+ and CD8+ cells, numerous macrophages of CD68+ and CD163+ phenotypes; no CAFs were identified. The other two patients were regarded as non-responders as at least 50% of the tumor was viable. The tumor microenvironment of these tumors was generally associated with a lesser extent of inflammatory response compared to the tongue tumor, a variable CD4+/CD8+ ratio and presence of CAFs. Neither T regulatory cells (FOXP3+) nor natural killer cells (CD56+, CD57+) were identified in any of the cases.Conclusion: We showed that characterizing the specific populations of immune-related cells and CAFs after treatment with pembrolizumab, may add to our understanding of the tumor-TME interactions in this setting. These findings should be investigated in future studies on a larger number of patients.

scholarly journals Nivolumab-induced adrenalitis

2019 ◽  
Vol 12 (11) ◽  
pp. e231829 ◽  
Author(s):  
Iqra Iqbal ◽  
Muhammad Atique Alam Khan ◽  
Waqas Ullah ◽  
Dina Nabwani
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Life Threatening ◽  
Line Chemotherapy

Immune checkpoint inhibitors (ICIs) are an evolving class of drugs for the treatment of various cancers; for example, their use is recommended as a second-line chemotherapy for non-small cell lung cancer. With the expanding use of ICIs, we are discovering their unique side effects, called immune-related adverse events (irAEs), which can impair gastrointestinal, hepatic, dermatological, endocrine and other systems. Nivolumab is an ICI that blocks the human programmed death receptor-1 (PD-1) on T cells to prevent the interaction between the receptor, PD-1, and human programmed death ligand-1 expressed on tumour cells. Here, we report a case of a 65-year-old woman with recurrent lung adenocarcinoma who was treated with nivolumab and developed immune-related adrenalitis, which was managed with hydrocortisone and fludrocortisone. This case highlights the importance of understanding the irAEs of ICIs to allow prompt recognition and management of life-threatening complications of the treatment.

scholarly journals Targeting the PD-1/PD-L1 Pathway in Renal Cell Carcinoma

2019 ◽  
Vol 20 (7) ◽  
pp. 1692 ◽  
Author(s):  
Solène-Florence Kammerer-Jacquet ◽  
Antoine Deleuze ◽  
Judikaël Saout ◽  
Romain Mathieu ◽  
Brigitte Laguerre ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Programmed Death ◽  
Pathologic Features ◽  
Death Receptor Ligand ◽  
Antiangiogenic Drugs

Renal cell carcinoma encompass distinct diseases with different pathologic features and distinct molecular pathways. Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1) / programmed death receptor 1 (PD-1) pathway alone or in combination have greatly changed clinical management of metastatic renal cell carcinoma, now competing with antiangiogenic drugs in monotherapy for first-line treatment. However, long-term response rates are low, and biomarkers are needed to predict treatment response. Quantification of PD-L1 expression by immunohistochemistry was developed as a promising biomarker in clinical trials, but with many limitations (different antibodies, tumour heterogeneity, specimens, and different thresholds of positivity). Other biomarkers, including tumour mutational burden and molecular signatures, are also developed and discussed in this review.

scholarly journals Predictive biomarkers of inhibitors immune checkpoints therapy in malignant tumors

2021 ◽  
Vol 8 (2) ◽  
pp. 73-83
Author(s):  
M. V. Kiselevsky ◽  
I. V. Samoylenko ◽  
O. V. Zharkova ◽  
N. V. Ziganshina ◽  
A. A. Petkevich ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Predictive Biomarkers ◽  
Peripheral Blood Lymphocytes ◽  
Immune Checkpoints ◽  
Russian Science ◽  
Programmed Death ◽  
Number Of Patients ◽  
Russian Science Citation Index

Immune checkpoint inhibitors (ICT) therapy is a successful immunotherapy (IT) strategy that is quite effective in a number of patients with non-small cell lung cancer, melanoma, bladder cancer, breast cancer and others. Nevertheless, there is a need in predictive markers for ICT therapy for personalized IT as far as there is a large group of patients, the proportion of which varies depending on the tumor, who do not have a clinical response to such therapy. The review summarizes the theoretical aspects and results of clinical trials dedicated to various clinical efficiency predictor using modern databases. As a result of the analysis it is established that the main candidates for the role of such markers are tumor infiltrating lymphocytes and their subpopulations, peripheral blood lymphocytes (PBL) and their subpopulations. PD1 (programmed death receptor 1) and PDL1 (programmed death receptor ligand 1) expression in tumor tissue can also be important for predicting IT efficiency. The most promising predictive biomarker meaning the most clinically relevant is a combination of the PBL subpopulations study and PD1 and PDL1 expression on the tumor cells.PubMed, Scopus, Web of Science, eLibrary, Russian Science Citation Index databases were searched for the available appropriate literature reports. The authors included 82 in the given review.

scholarly journals IMMU-26. DISEASE CONTROL IN A PEDIATRIC PATIENT WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) AND SOMATIC HIGH MICROSATELLITE INSTABILITY (MSI-H) WITH PD-1 INHIBITOR NIVOLUMAB (NIVO) ONLY AND NO FOCAL RADIOTHERAPY (RT)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii365-iii365
Author(s):  
Trisha Larkin ◽  
Jason Blatt ◽  
Sridharan Gururangan
Keyword(s):  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Left Frontal Lobe ◽  
Who Grade ◽  
Programmed Death ◽  
Uncertain Significance ◽  
Second Resection ◽  
Newly Diagnosed Glioblastoma ◽  
History Of ◽  
To Receive

Abstract Immune checkpoint inhibitors that target programmed death receptor-1 (PD-1) have recently been shown to be a promising option for the management of recurrent mismatch repair (MMR) deficient GBM following radiotherapy. We report a case of a 9-year-old boy who presented with a 6 week history of frontal headaches and was found to have a left frontal lobe mass. Pathology obtained from a gross total resection (GTR) was consistent with classic GBM, WHO Grade IV. Neuroimaging four weeks following initial resection was remarkable for local recurrence. The patient underwent another GTR of the tumor at our center. While pathology again confirmed GBM, GlioSequencing of tumor tissue from second resection showed MSI-H, NF2 mutation p.R338H, NF1 mutations p.R2450* and pI193Yfs*11, TP53 mutations p.R213* and p.R273C, EGFR mutation, and multiple variants of uncertain significance. Germline testing was negative for MMR deficiency or other deleterious mutations. Parents opted to defer radiotherapy and consented to monotherapy treatment with Nivolumab (Opdivo, BMS pharmaceuticals, USA), a PD-1 inhibitor, at a dose of 3 mg/kg administered every two weeks. Our patient is now 22 months post-second resection and continues to receive Nivolumab without evidence of recurrent disease or adverse autoimmune effects from PD-1 blockade. He has remained in school with good academic performance and has exhibited no regression of functional status during the entirety of his treatment course. This case provides evidence of possible efficacy of PD-1 blockade without focal radiotherapy in this child with GBM and somatic MSI instability.

scholarly journals Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II—The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer

2017 ◽  
Vol 142 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Esmeralda Celia Marginean ◽  
Barbara Melosky
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Microsatellite Instability ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Immune Checkpoints ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

Context.— The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti–programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability–high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability–high CRC. Objectives.— To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. Data Sources.— A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. Conclusions.— Exciting success with anti–PD-1/PD-L1 and anticytotoxic T-lymphocyte–associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability–high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti–PD-1 or anti–PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability–high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.

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