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anti pd 1 melanoma

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https://www.readbyqxmd.com/read/28222231/two-cases-of-anti-programmed-cell-death-1-associated-bullous-pemphigoid-like-disease-and-eruptive-keratoacanthomas-featuring-combined-histopathology
#1
Justin P Bandino, David M Perry, Christina E Clarke, Richard M Marchell, Dirk M Elston
Programmed cell death protein 1 (PD-1) inhibitors (pembrolizumab, nivolumab) are novel immunotherapies revolutionizing the management of advanced malignancy with an improved adverse effect profile, yet the immune-related side effects are still being characterized.(1,2) We report the unique concurrence of bullous pemphigoid-like disease (BP) with keratoacanthomas and squamous cell carcinomas in two patients receiving anti-PD-1 immunotherapy for metastatic melanoma. This article is protected by copyright. All rights reserved...
February 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28214657/ipilimumab-alone-or-in-combination-with-nivolumab-after-progression-on-anti-pd-1-therapy-in-advanced-melanoma
#2
Lisa Zimmer, Susmitha Apuri, Zeynep Eroglu, Lisa A Kottschade, Andrea Forschner, Ralf Gutzmer, Max Schlaak, Lucie Heinzerling, Angela M Krackhardt, Carmen Loquai, Svetomir N Markovic, Richard W Joseph, Kelly Markey, Jochen S Utikal, Carsten Weishaupt, Simone M Goldinger, Vernon K Sondak, Jonathan S Zager, Dirk Schadendorf, Nikhil I Khushalani
BACKGROUND: The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28211077/severe-bullous-pemphigoid-associated-with-pembrolizumab-therapy-for-metastatic-melanoma-with-complete-regression
#3
O Rofe, G Bar-Sela, Z Keidar, T Sezin, C D Sadik, R Bergman
Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]...
February 16, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28204866/vedolizumab-treatment-for-immune-checkpoint-inhibitor-induced-enterocolitis
#4
Viktoria Bergqvist, Erik Hertervig, Peter Gedeon, Marija Kopljar, Håkan Griph, Sara Kinhult, Ana Carneiro, Jan Marsal
Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy...
February 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28202513/myeloid-cells-that-impair-immunotherapy-are-restored-in-melanomas-which-acquire-resistance-to-braf-inhibitors
#5
Shannon M Steinberg, Tamer Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian Malik, Tammara Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael Whitfield, Mary Jo Turk
Acquired resistance to BRAFV600E inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given the plastic nature of cancers. While there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment initially reduced by BRAFi treatment...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197351/a-case-of-malignant-melanoma-of-the-uterine-cervix-with-disseminated-metastases-throughout-the-vaginal-wall
#6
Tomoko Noguchi, Nami Ota, Yasushi Mabuchi, Shigetaka Yagi, Sawako Minami, Hisako Okuhira, Yuki Yamamoto, Yasushi Nakamura, Kazuhiko Ino
Malignant melanoma (MM) in the female genital tract accounts for less than 2% of all melanomas, and the vast majority associated occur in the vulva and vagina. Primary MM of the uterine cervix is extremely rare and its prognosis is very poor. We report a case of primary MM of the cervix with dissemination throughout the vaginal wall. A 66-year-old woman presented with postmenopausal bleeding. Gynecologic examination demonstrated a 2 cm polypoid blackish-pigmented tumor on the cervix with multiple small blackish-pigmented lesions throughout the vaginal wall...
2017: Case Reports in Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28193624/transcriptional-mechanisms-of-resistance-to-anti-pd-1-therapy
#7
Maria Libera Ascierto, Alvin Makohon-Moore, Evan J Lipson, Janis M Taube, Tracee L McMiller, Alan E Berger, Jinshui Fan, Genevieve Kaunitz, Tricia Cottrell, Zachary Kohutek, Alexander Favorov, Vladimir Makarov, Nadeem Riaz, Timothy A Chan, Leslie Cope, Ralph H Hruban, Drew M Pardoll, Barry S Taylor, David B Solit, Christine A Iacobuzio-Donahue, Suzanne L Topalian
PURPOSE: To explore factors associated with response and resistance to anti-PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient with widely metastatic melanoma who had a heterogeneous response. MATERIALS AND METHODS: Twenty-six melanoma specimens (four pre-mortem, 22 post-mortem) were subjected to whole-exome sequencing. Candidate immunologic markers and gene expression were assessed in ten cutaneous metastases showing response or progression during therapy...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28190531/cutaneous-adverse-effects-of-the-immune-checkpoint-inhibitors
#8
REVIEW
Lindsey K Collins, M Shane Chapman, Joi B Carter, Faramarz H Samie
The immune checkpoint targeted agents, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and anti-programed cell death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitors are frequently associated with cutaneous side effects that are often dose limiting and can lead to discontinuation of therapy. Ipilimumab, a CTLA-4 inhibitor, is most commonly associated with a morbilliform eruption on the trunk and extremities and pruritus. More severe cutaneous toxicities reported include toxic epidermal necrolysis and severe drug rash with eosinophila and systemic symptoms...
December 14, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28188628/histopathological-aspects-of-cutaneous-erythematous-papular-eruptions-induced-by-immune-checkpoint-inhibitors-for-the-treatment-of-metastatic-melanoma
#9
Raul E Perret, Nicolas Josselin, Anne-Chantal Knol, Amir Khammari, Julie Cassecuel, Lucie Peuvrel, Brigitte Dreno
BACKGROUND: Immune checkpoint blockade therapy (ICBT) for the treatment of melanoma has led to an important improvement of overall survival in advanced stage patients. However, secondary cutaneous maculopapular eruptions (CMPEs) are frequent and remain poorly characterized. METHODS: We performed a retrospective analysis of melanoma patients from our institution who developed CMPEs during ICBT. Clinical information was retrieved, and histopathological and immunohistochemical characterization was performed by two pathologists...
February 10, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28184224/cbl-b-deficiency-mediates-resistance-to-programmed-death-ligand-1-programmed-death-1-regulation
#10
Mai Fujiwara, Emily J Anstadt, Robert B Clark
Casitas B-lineage lymphoma-b (Cbl-b) is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) T cells are hyper-reactive and co-stimulation independent, and Cbl-b(-/-) mice demonstrate robust T cell and NK cell-mediated antitumor immunity. As a result of these murine studies, Cbl-b is considered a potential target for therapeutic manipulation in human cancer immunotherapy. The PD-L1/PD-1 pathway of immune regulation is presently an important therapeutic focus in tumor immunotherapy, and although Cbl-b(-/-) mice have been shown to be resistant to several immuno-regulatory mechanisms, the sensitivity of Cbl-b(-/-) mice to PD-L1-mediated suppression has not been reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28181070/combining-forces-the-promise-and-peril-of-synergistic-immune-checkpoint-blockade-and-targeted-therapy-in-metastatic-melanoma
#11
David J Hermel, Patrick Ott
Both immune checkpoint inhibitors and molecularly targeted agents have dramatically improved clinical outcomes for patients with metastatic melanoma. These two therapeutic approaches harness distinct mechanistic pathways-on the one hand, monoclonal antibodies against the immune checkpoints CTLA-4 and PD-1/PD-L1 stimulate the T cell mediated host immune response, while targeted inhibitors of the proto-oncogenes BRAF and MEK disrupt constitutive kinase activity responsible for tumor growth. The prospect of combining these two treatment modalities has been proposed as a potential way to increase overall response rate, extend durability of the anti-tumor response, and circumvent the immune-mediated resistance to targeted therapy...
February 8, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28174141/checkpoint-inhibition-for-advanced-mucosal-melanoma
#12
Julia Thierauf, Johannes A Veit, Jochen Hess, Nicolai Treiber, Catharina Lisson, Stephanie E Weissinger, Martin Bommer, Thomas K Hoffmann
BACKGROUND: Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. OBJECTIVES: To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. MATERIAL & METHODS: We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage...
February 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28171845/a-first-reported-case-of-metastatic-anorectal-amelanotic-melanoma-with-a-marked-response-to-anti-pd-1-antibody-nivolumab-a-case-report
#13
Katsuji Tokuhara, Kazuyoshi Nakatani, Hirotsugu Tanimura, Kazuhiko Yoshioka, Takahiro Kiyohara, Masanori Kon
INTRODUCTION: Anorectal amelanotic melanoma (AAMM) is a rare disease with poor prognosis. A standard treatment strategy for AAMM has not been established. PRESENTATION OF CASE: We report a case of successful treatment of AAMM with nivolumab. A 67-year-old man was referred for colonoscopy which revealed type I tumor in the rectum. AAMM was diagnosed with immunostaining histopathological biopsy findings. Enhanced computed tomography (ECT) revealed the rectal tumor without distant organ metastasis...
January 23, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28166182/vogt-koyanagi-harada-like-syndrome-complicating-pembrolizumab-treatment-for-metastatic-melanoma
#14
Marion Bricout, Adeline Petre, Mona Amini-Adle, Widad Bezza, Pascal Seve, Laurent Kodjikian, Stéphane Dalle, Luc Thomas
Vogt-Koyanagi-Harada (VKH) syndrome is a rare condition implicating systemic immune reaction against melanocytes. The pathophysiology is unclear. A genetic predisposition has been suggested as HLA-DR4/DRB1*04 is more common among VKH patients. Drug induced VKH syndrome has been reported in advanced melanoma patients receiving immunotherapy, including ipilimumab and adoptive cell transfer of Tumor-Infiltrating Lymphocyte associated with IL-2. To date, no case of anti PD-1 -induced VKH syndrome has been described...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28148715/the-exportin-1-inhibitor-selinexor-exerts-superior-anti-tumor-activity-when-combined-with-t-cell-checkpoint-inhibitors
#15
Matthew R Farren, Rebecca C Hennessey, Reena Shakya, Omar Elnaggar, Gregory Young, Kari Kendra, Yosef Landesman, Sivan Elloul, Marsha Crochiere, Boris Klebanov, Trinayan Kashyap, Christin E Burd, Gregory B Lesinski
Selinexor, a Selective Inhibitor of Nuclear Export (SINE) compound targeting exportin-1, has previously been shown to inhibit melanoma cell growth in vivo. We hypothesized that combining selinexor with antibodies that block or disrupt T cell checkpoint molecule signaling would exert superior anti-melanoma activity. In vitro, selinexor increased PD-1 and CTLA4 gene expression in leukocytes and induced PD L1 gene expression in human melanoma cell lines. Mice bearing syngeneic B16F10 melanoma tumors demonstrated a significant reduction in tumor growth rate in response to the combination of selinexor and anti-PD-1 or anti-PD-L1 antibodies (p<0...
February 1, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28137295/a-phase-ii-trial-of-stereotactic-body-radiotherapy-with-concurrent-anti-pd1-treatment-in-metastatic-melanoma-evaluation-of-clinical-and-immunologic-response
#16
Katrien De Wolf, Vibeke Kruse, Nora Sundahl, Mireille van Gele, Ines Chevolet, Reinhart Speeckaert, Lieve Brochez, Piet Ost
BACKGROUND: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients...
January 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28129544/genomic-and-transcriptomic-features-of-response-to-anti-pd-1-therapy-in-metastatic-melanoma
#17
Willy Hugo, Jesse M Zaretsky, Lu Sun, Chunying Song, Blanca Homet Moreno, Siwen Hu-Lieskovan, Beata Berent-Maoz, Jia Pang, Bartosz Chmielowski, Grace Cherry, Elizabeth Seja, Shirley Lomeli, Xiangju Kong, Mark C Kelley, Jeffrey A Sosman, Douglas B Johnson, Antoni Ribas, Roger S Lo
No abstract text is available yet for this article.
January 26, 2017: Cell
https://www.readbyqxmd.com/read/28127529/organizing-pneumonia-following-treatment-with-pembrolizumab-for-metastatic-malignant-melanoma-a-case-report
#18
R Kuint, M Lotem, T Neuman, E Bekker-Milovanov, A Abutbul, U Laxer, N Berkman, Z G Fridlender
Pembrolizumab is a monoclonal antibody against the programmed cell death 1 (PD-1) receptor, and is widely used for the treatment of various malignancies, most commonly malignant melanoma. Here we report the first documented and pathology proven case of Organizing Pneumonia complicating treatment with Pembrolizumab. This was a man who presented with a dense lung consolidation four months following treatment with Pembrolizumab. A thorough microbiological workup was negative and his findings did not improve with broad spectrum anti-microbial treatment...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28121940/not-only-for-melanoma-subcutaneous-pseudoprogression-in-lung-squamous-cell-carcinoma-treated-with-nivolumab-a-case-report
#19
Michal Sarfaty, Assaf Moore, Elizabeth Dudnik, Nir Peled
RATIONALE: Pseudoprogression, that is, initial tumor growth followed by subsequent tumor regression, has been well described for immunomodulation therapy in melanoma patients. This phenomenon is not well defined in lung cancer. Nivolumab, an anti-PD-1 monoclonal antibody, was recently approved for nonsmall cell lung cancer (NSCLC) as a second-line therapy. PATIENT CONCERNS AND DIAGNOSIS: We present a patient with squamous NSCLC, suffering from multiple bone and subcutaneous metastases...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28114249/inhibitors-of-cytotoxic-t-lymphocyte-antigen-4-and-programmed-death-1-programmed-death-1-ligand-for-metastatic-melanoma-dual-versus-monotherapy-summary-of-advances-and-future-directions-for-studying-these-drugs
#20
Kimberly Loo, Adil I Daud
Immense progress in the field of cancer immunotherapy has garnered several novel and successful treatments for metastatic melanoma. Beginning with therapies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), objective response rates, overall survival, and long-term survival were significantly increased when compared with glycoprotein 100 vaccine therapies. Expanding the breadth of therapies aimed to "release the breaks" on the active immune system, anti-programmed death 1 (PD-1) and anti-programmed death 1 ligand (PD-L1) therapies further improved overall survival, progression-free survival, and objective tumor response while exhibiting more favorable safety profiles compared with ipilimumab and to chemotherapy agents...
January 2017: Cancer Journal
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