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https://www.readbyqxmd.com/read/28093620/inflammatory-bowel-disease-and-cancer-response-due-to-anti-ctla-4-is-it-in-the-flora
#1
REVIEW
Franck Carbonnel, Emilie Soularue, Clélia Coutzac, Nathalie Chaput, Christine Mateus, Patricia Lepage, Caroline Robert
Checkpoint inhibitors blocking CTLA-4 (ipilimumab) and PD-1 (nivolumab, pembrolizumab) have transfigured our cancer treatment paradigm. However, these drugs can induce immune-related adverse events that share clinical and pathological characteristics with immune-mediated diseases. One of the most severe immune-related adverse event observed with anti-CTLA-4 is an enterocolitis that mirrors naturally occurring inflammatory bowel disease. This paper reviews the clinical, immunological, and microbiota data associated with the immune-related enterocolitis induced by the cancer immunotherapy blocking CTLA-4, ipilimumab...
January 16, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28076863/adverse-renal-effects-of-immune-checkpoint-inhibitors-a-narrative-review
#2
Rimda Wanchoo, Sabine Karam, Nupur N Uppal, Valerie S Barta, Gilbert Deray, Craig Devoe, Vincent Launay-Vacher, Kenar D Jhaveri
BACKGROUND: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. SUMMARY: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity...
January 12, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28073845/agreement-between-programmed-cell-death-ligand-1-diagnostic-assays-across-multiple-protein-expression-cut-offs-in-non-small-cell-lung-cancer
#3
Marianne J Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Marietta Scott, Paul Scorer, Hytham Al-Masri, Marlon Rebelatto, Jill Walker
PURPOSE: agents:Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized and different assay methods could lead to inappropriate treatment selection...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28064556/pd-1-checkpoint-blockade-alone-or-combined-pd-1-and-ctla-4-blockade-as-immunotherapy-for-lung-cancer
#4
Tawee Tanvetyanon, Jhanelle E Gray, Scott J Antonia
Signaling through T-cell surface, an immune checkpoint protein such as PD-1 or CTLA-4 helps dampen or terminate unwanted immune responses. Blocking a single immune checkpoint or multiple checkpoints simultaneously can generate anti-tumor activity against a variety of cancers including lung cancer. Area covered: This review highlights the results of recent clinical studies of single or combination checkpoint inhibitor immunotherapy in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). The authors discuss pembrolizumab and pembrolizumab plus ipilimumab, durvalumab and durvalumab plus tremelimumab, nivolumab and nivolumab plus ipilimumab for NSCLC as well as nivolumab and nivolumab plus ipilimumab for SCLC...
January 9, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28062513/metastatic-melanoma-patient-had-complete-response-with-clonal-expansion-after-whole-brain-radiation-and-pd-1-blockade
#5
Cara L Haymaker, DaeWon Kim, Marc Uemura, Luis M Vence, Ann Phillip, Natalie McQuail, Paul D Brown, Irina Fernandez, Courtney W Hudgens, Caitlin Creasy, Wen-Jen Hwu, Padmanee Sharma, Michael T Tetzlaff, James P Allison, Patrick Hwu, Chantale Bernatchez, Adi Diab
We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy (WBRT) followed by the PD-1 inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8(+) T cells in the blood expanded and the ratio of CD8(+):Treg T cells increased. A CD8(+) T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone...
January 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28057177/les-inhibiteurs-des-points-de-contr%C3%A3-le-immunitaire-dans-le-cancer-bronchique-non-%C3%A3-petites-cellules-de-stade-avanc%C3%A3
#6
Elizabeth Fabre, Nicola Pécuchet, Jacques Cadranel
IMMUNE CHECKPOINT INHIBITORS IN ADVANCED NON-SMALL CELL LUNG CANCER: T-cell-directed strategies represent currently a major advance in the treatment of advanced non-small-cell lung cancer, regarding their efficacy and tolerance. Nivolumab and pembrolizumab, two monoclonal antibodies targeting programmed cell death protein 1 (PD-1) have shown their efficacy in phase III studies. Several other drugs are developed and the benefit of association is being evaluated. In this article, we propose to summarize the clinical development of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28057176/immunoth%C3%A3-rapie-et-m%C3%A3-lanome-l%C3%A2-exemple-des-anticorps-immunomodulateurs
#7
Cécile Pagès, Barouyr Baroudjian, Celeste Lebbé
Recently, metastatic melanoma has known real therapeutic improvement. Since 2011, 8 drugs have been approved for advanced melanoma such as immunotherapy checkpoint inhibitors. Chemotherapy is no longer used in the first setting of metastatic melanoma treatment. In 2010, the advent of ipilimumab, an anti CTLA 4 inhibitor, changed the scenario and in the following years, many studies confirmed the efficacy of nivolumab and pembrolizumab, two anti PD 1 inhibitors, as a first line treatment. Furthermore, the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28056412/toxicity-of-concurrent-stereotactic-radiotherapy-and-targeted-therapy-or-immunotherapy-a-systematic-review
#8
REVIEW
Stephanie G C Kroeze, Corinna Fritz, Morten Hoyer, Simon S Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
BACKGROUND AND PURPOSE: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. MATERIAL AND METHODS: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK"...
December 19, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#9
Burak Bilgin, Mehmet An Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most of the Gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aimed to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in the era of published or reported recent studies...
January 5, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28054320/pembrolizumab-for-advanced-melanoma-experience-from-the-spanish-expanded-access-program
#10
M González-Cao, A Arance, J M Piulats, I Marquez-Rodas, J L Manzano, A Berrocal, G Crespo, D Rodriguez, E Perez-Ruiz, M Berciano, A Soria, A G Castano, E Espinosa, C Montagut, L Alonso, T Puertolas, C Aguado, M A Royo, R Blanco, J F Rodríguez, E Muñoz, P Mut, F Barron, S Martin-Algarra
BACKGROUND: The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. METHODS: Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group...
January 4, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28045203/pd-l1-expression-and-survival-among-melanoma-patients-treated-with-standard-immunotherapy-or-chemotherapy
#11
T Steiniche, A Vestergaard Danielsen, Z Wang, Y Feng, P Switten Nielsen, L Bastholt, H Schmidt, I M Svane, M Dolled-Filhart, K Emancipator, R Weiner, M Busch-Sørensen, W Zhou
The association between programmed death ligand 1 (PD-L1) expression and survival among melanoma patients treated with chemotherapy is unclear.(1-5) We retrospectively characterized PD-L1 levels in patients with melanoma treated at Aarhus University Hospital in Denmark (2001-2012) using a prototype immunohistochemistry assay (QualTek Molecular Laboratories, Goleta, California, USA) and investigated the association between PD-L1 and overall survival (OS) in patients who received chemotherapy or immunotherapy (interleukin-2, interferon, ipilimumab)...
January 3, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28029020/clinical-update-in-aspects-of-the-management-of-autoimmune-thyroid-diseases
#12
REVIEW
Duncan J Topliss
Aspects of autoimmune thyroid disease updated in this review include: immunoglobulin G4 (IgG4)-related thyroid disease (Riedel's thyroiditis, fibrosing variant of Hashimoto's thyroiditis, IgG4-related Hashimoto's thyroiditis, and Graves' disease with elevated IgG4 levels); recent epidemiological studies from China and Denmark indicating that excess iodine increases the incidence of Hashimoto's thyroiditis and hypothyroidism; immunomodulatory agents (ipilimumab, pembrolizumab, nivolumab) activate immune response by inhibiting T-cell surface receptors which down-regulate immune response, i...
December 2016: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28028828/thyroid-abnormalities-following-the-use-of-ctla-4-and-pd-1-inhibitors-in-the-treatment-of-melanoma
#13
D L Morganstein, Z Lai, L Spain, S Diem, D Levine, C Mace, M Gore, J Larkin
CONTEXT: Checkpoint inhibitors are emerging as important cancer therapies, but are associated with a high rate of immune side effects, including endocrinopathy. OBJECTIVE: To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course. DESIGN AND PATIENTS: Consecutive patients with melanoma treated with either Ipilimumab, Nivolumab, Pembrolizumab or the combination of Ipilimumab and Nivolumab were identified...
December 27, 2016: Clinical Endocrinology
https://www.readbyqxmd.com/read/28025978/immune-targets-and-neoantigens-for-cancer-immunotherapy-and-precision-medicine
#14
REVIEW
Rong-Fu Wang, Helen Y Wang
Harnessing the immune system to eradicate malignant cells is becoming a most powerful new approach to cancer therapy. FDA approval of the immunotherapy-based drugs, sipuleucel-T (Provenge), ipilimumab (Yervoy, anti-CTLA-4), and more recently, the programmed cell death (PD)-1 antibody (pembrolizumab, Keytruda), for the treatment of multiple types of cancer has greatly advanced research and clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical trials, using NY-ESO-1-specific T cell receptor (TCR) or CD19-chimeric antigen receptor (CAR), have shown promising clinical results for patients with metastatic cancer...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28025384/renal-effects-of-immune-checkpoint-inhibitors
#15
Hassan Izzedine, Christine Mateus, Céline Boutros, Caroline Robert, Philippe Rouvier, Zahir Amoura, Alexis Mathian
Recent advances in immune checkpoint inhibitor (ICPI) development have led to major improvements in oncology patient outcomes. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are two essential immune checkpoint receptors. Ipilimumab and tremelimumab (anti-CTLA-4-blocking antibodies) and pembrolizumab and nivolumab (antibodies targeting PD-1 receptors) have already been approved by US Food and Drug Administration in several malignancies. Two different forms of ICPI-induced renal damage have been identified, including acute (granulomatous) tubulointerstitial nephritis and immune complex glomerulonephritis...
December 26, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28011498/metastatic-pattern-of-stage-iv-colorectal-cancer-with-high-frequency-microsatellite-instability-as-a-prognostic-factor
#16
Kenji Fujiyoshi, Gou Yamamoto, Takashi Takenoya, Akemi Takahashi, Yoshiko Arai, Mina Yamada, Miho Kakuta, Kensei Yamaguchi, Yoshito Akagi, Yoji Nishimura, Hirohiko Sakamoto, Kiwamu Akagi
BACKGROUND: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear. PATIENTS AND METHODS: A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF)...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/28006927/the-safety-of-therapeutic-monoclonal-antibodies-implications-for-cancer-therapy-including-immuno-checkpoint-inhibitors
#17
R Demlova, D Valík, R Obermannova, L ZdraŽilová-Dubská
Monoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies for both hematologic malignancies and solid tumors. In addition to targeting cancer antigens antibodies can also modulate immunological pathways that are critical to immune surveillance. Antibody therapy directed against several negative immunologic regulators (checkpoints) is demonstrating significant success in the past few years. Immune checkpoint inhibitors, ipilimumab, pembrolizumab and nivolumab, have shown significant clinical benefit in several malignancies and are already approved for advanced melanoma and squamous NSCLC...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/27998967/antibody-mediated-thyroid-dysfunction-during-t-cell-checkpoint-blockade-in-patients-with-non-small-cell-lung-cancer
#18
J C Osorio, A Ni, J E Chaft, R Pollina, M K Kasler, D Stephens, C Rodriguez, L Cambridge, H Rizvi, J D Wolchok, T Merghoub, C M Rudin, S Fish, M D Hellmann
BACKGROUND: PD-1 blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated, although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features have not been previously described. PATIENT AND METHODS: Patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (N=51) as part of KEYNOTE-001 (NCT01295827) were included...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27997006/-nivolumab-in-second-line-treatment-of-squamous-non-small-cell-lung-cancer
#19
Filippo De Marinis, Antonio Passaro
The treatment of non-small cell lung cancer (NSCLC) is changing dramatically in the last period, considering both non-squamous and squamous disease. In the last five years, the identification of different molecular predictive biomarker (e.g., EGFR, ALK e ROS1) and the utilize of new chemotherapy agents associated or not with antiangiogenics agents (e.g., bevacizumab and nintedanib), allowed the improvement of survival and related responses to these treatments. However, these advances, did not allow an improvement of the same endpoints in the management of NSCLC with squamous cell histology (SCC), where until very recently, docetaxel in monotherapy remained as a corner stone treatment for the second line, although associated with an unfavorable toxicity profile...
December 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27993808/pembrolizumab-induced-bulbar-myopathy-and-respiratory-failure-with-necrotizing-myositis-of-the-diaphragm
#20
C L Haddox, N Shenoy, J C Kao, K K Shah, S Jain, T R Halfdanarson, E F Wijdicks, M P Goetz
No abstract text is available yet for this article.
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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