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Ipilimumab

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https://www.readbyqxmd.com/read/28214657/ipilimumab-alone-or-in-combination-with-nivolumab-after-progression-on-anti-pd-1-therapy-in-advanced-melanoma
#1
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/28214654/programmed-cell-death-protein-1-pd-1-inhibitor-therapy-in-patients-with-advanced-melanoma-and-preexisting-autoimmunity-or-ipilimumab-triggered-autoimmunity
#2
Ralf Gutzmer, Anika Koop, Friedegund Meier, Jessica C Hassel, Patrick Terheyden, Lisa Zimmer, Lucie Heinzerling, Selma Ugurel, Claudia Pföhler, Anja Gesierich, Elisabeth Livingstone, Imke Satzger, Katharina C Kähler
AIM: Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited. PATIENTS AND METHODS: Metastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-1i from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-1i 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/28207422/ipilimumab-induced-sarcoidosis-and-thyroiditis
#4
Sravanthi Nandavaram, Anupa Nadkarni
No abstract text is available yet for this article.
February 15, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28204866/vedolizumab-treatment-for-immune-checkpoint-inhibitor-induced-enterocolitis
#5
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/28190531/cutaneous-adverse-effects-of-the-immune-checkpoint-inhibitors
#6
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/28183255/melanoma-adjuvant-treatment-current-insight-and-clinical-features
#7
Carmine D Aniello, Francesco Perri, Giuseppina Della Vittoria Scarpati, Chiara Della Pepa, Salvatore Pisconti, Vincenzo Montesarchio, Nicolas Wernert, Mayra Rachele Zarone, Michele Caraglia, Gaetano Facchini, Massimiliano Berretta, Carla Cavaliere
Melanoma represents 2-3% of all cancers, 95% of them arise from skin, while only 5% are non-cutaneous melanoma. Despite an optimal surgery management, the risk of a local and systemic relapse remains high, particularly in high-risk patients (node-positive or node-negative T3b, T4 a/b). We conducted a systematic review of the main published and ongoing phase I/II/III trials between 2000 and June 2015 on the adjuvant treatment of cutaneous melanoma. The IFN remains the only option currently available for this aim...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28179454/fda-approval-summary-pembrolizumab-for-the-treatment-of-patients-with-unresectable-or-metastatic-melanoma
#8
Amy Barone, Maitreyee Hazarika, Marc R Theoret, Pallavi Mishra-Kalyani, Huanyu Chen, Kun He, Rajeshwari Sridhara, Sriram Subramaniam, Elimika Pfuma, Yaning Wang, Hongshan Li, Hong Zhao, Jeanne Fourie Zirkelbach, Patricia Keegan, Richard Pazdur
On December 18, 2015, the U.S. Food and Drug Administration (FDA) granted regular approval to pembrolizumab (KEYTRUDA®; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma, based on results of two randomized, open-label, active-controlled clinical trials. In Trial PN006, 834 patients with ipilimumab-naïve metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg intravenously (IV) every 2 (q2w) or 3 (q3w) weeks until disease progression or ipilimumab 3 mg/kg q3w for up to four doses...
February 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28176947/silencing-of-foxp3-enhances-the-antitumor-efficacy-of-gm-csf-genetically-modified-tumor-cell-vaccine-against-b16-melanoma
#9
Antonio Miguel, Luis Sendra, Verónica Noé, Carles J Ciudad, Francisco Dasí, David Hervas, María José Herrero, Salvador F Aliño
The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg), which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28173241/severe-hepatitis-arising-from-ipilimumab-administration-following-melanoma-treatment-with-nivolumab
#10
Ryota Tanaka, Yasuhiro Fujisawa, Inoue Sae, Hiroshi Maruyama, Shusaku Ito, Naoyuki Hasegawa, Ikuo Sekine, Manabu Fujimoto
No abstract text is available yet for this article.
February 11, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28167454/peripheral-cd8-effector-memory-type-1-t-cells-correlate-with-outcome-in-ipilimumab-treated-stage-iv-melanoma-patients
#11
Kilian Wistuba-Hamprecht, Alexander Martens, Florian Heubach, Emanuela Romano, Marnix Geukes Foppen, Jianda Yuan, Michael Postow, Phillip Wong, Domenico Mallardo, Bastian Schilling, Anna Maria Di Giacomo, Amir Khammari, Brigitte Dreno, Michele Maio, Dirk Schadendorf, Paolo A Ascierto, Jedd D Wolchok, Christian U Blank, Claus Garbe, Graham Pawelec, Benjamin Weide
The role of the assessment of peripheral T-cell phenotypes in predicting overall survival (OS) after ipilimumab treatment is unclear. Here, we analysed mononuclear cells in the blood before and at different time points during treatment with ipilimumab in 137 late-stage melanoma patients. The proportions of baseline naïve and memory T-cells were measured by flow cytometry and correlated with OS, with an emphasis on PD-1 expression. High frequencies (>13%) of CD8 effector-memory type 1 (EM1) T-cells at baseline correlated with longer OS (p = 0...
February 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28166182/vogt-koyanagi-harada-like-syndrome-complicating-pembrolizumab-treatment-for-metastatic-melanoma
#12
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/28163001/adjuvant-ipilimumab-for-stage-iii-melanoma-the-patient-voice
#13
Michael Brundage, Timothy Hanna
No abstract text is available yet for this article.
February 2, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28162999/health-related-quality-of-life-with-adjuvant-ipilimumab-versus-placebo-after-complete-resection-of-high-risk-stage-iii-melanoma-eortc-18071-secondary-outcomes-of-a-multinational-randomised-double-blind-phase-3-trial
#14
Corneel Coens, Stefan Suciu, Vanna Chiarion-Sileni, Jean-Jacques Grob, Reinhard Dummer, Jedd D Wolchok, Henrik Schmidt, Omid Hamid, Caroline Robert, Paolo A Ascierto, Jon M Richards, Celeste Lebbé, Virginia Ferraresi, Michael Smylie, Jeffrey S Weber, Michele Maio, Andrew Bottomley, Srividya Kotapati, Veerle de Pril, Alessandro Testori, Alexander M M Eggermont
BACKGROUND: The EORTC 18071 phase 3 trial compared adjuvant ipilimumab with placebo in patients with stage III melanoma. The primary endpoint, recurrence-free survival, was significantly longer in the ipilimumab group than in the placebo group. Investigator-reported toxic effects of ipilimumab consisted mainly of skin, gastrointestinal, endocrine, and hepatic immune-related adverse events. Adjuvant treatment with ipilimumab in this setting was approved in October, 2014, by the US Food and Drug Administration based on the results of the primary outcome of this trial...
February 2, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28146044/checkpoint-inhibitor-associated-drug-reaction-with-eosinophilia-and-systemic-symptom-syndrome
#15
Sayeef Mirza, Ebone' Hill, Steven P Ludlow, Sowmya Nanjappa
Drug reaction with eosinophilia and systemic symptom syndrome is a potentially fatal drug reaction that must be recognized quickly. Ipilimumab and nivolumab are both important agents in the treatment of melanoma and continue to be studied in other malignancies. We believe the mainstay of therapy for immunotherapy-induced drug reaction with eosinophilia and systemic symptom syndrome is early recognition, discontinuation of the inciting agent, supportive care, and treatment with high dose corticosteroids with appropriate tapers that may reduce the length of internal organ injury in cases with liver or kidney involvement...
January 31, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28141932/an-expanded-portfolio-of-survival-metrics-for-assessing-anticancer-agents
#16
Jennifer Karweit, Srividya Kotapati, Samuel Wagner, James W Shaw, Steffan W Wolfe, Amy P Abernethy
OBJECTIVES: With the introduction of more effective anticancer agents that prolong survival, there is a need for new methods to define the clinical value of treatments. The objective of this preliminary qualitative and quantitative analysis was to assess the utility of an expanded portfolio of survival metrics to differentiate the value of anticancer agents. STUDY DESIGN: A literature review was conducted of phase 3 trial data, reported in regulatory submissions within the last 10 years of agents for 6 metastatic cancers (breast cancer, colorectal cancer [CRC], melanoma, non-small cell lung cancer [NSCLC], prostate cancer [PC], and renal cell cancer [RCC])...
January 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28128877/endoscopic-findings-of-ipilimumab-induced-colitis
#17
Tatsunori Satoh, Kazuya Ohno, Takafumi Kurokami
Ipilimumab is a fully humanized monoclonal antibody targeting inhibitory cytotoxic T-lymphocyte-associated antigen-4 on T cells, thereby enhancing antitumor immunity.(1) While ipilimumab has significant therapeutic benefit, it induces hypersensitivity reactions in some targeted organs. Ipilimumab-induced colitis (IiC) is one such hypersensitivity reaction, clinically manifesting as colitis.(2) Colonoscopy is helpful in diagnosing IiC. The macroscopic and microscopic features of IiC include friable erythematous mucosa and ulcers with an absent vascular pattern...
January 27, 2017: Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society
https://www.readbyqxmd.com/read/28128709/eosinophilic-count-as-a-biomarker-for-prognosis-of-melanoma-patients-and-its-importance-in-the-response-to-immunotherapy
#18
Alvaro Moreira, Waltraud Leisgang, Gerold Schuler, Lucie Heinzerling
AIM: The prognostic role of eosinophils in cancer has been controversial. Some entities such as gastrointestinal cancers show a better survival, while others such as Hodgkin's lymphoma a worse survival in patients with eosinophilia. Patients who exhibited an increase in eosinophils upon therapy with ipilimumab or pembrolizumab were shown to survive longer. We wanted to investigate whether eosinophilia is a prognostic marker in metastatic melanoma. METHODS: In total, 173 patients with metastatic melanoma from our data base (median age 60 years; n = 86 with immunotherapy, n = 87 without immunotherapy) were analyzed for eosinophil counts and survival over the course of 12 years...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/28125365/cost-effectiveness-of-pembrolizumab-versus-ipilimumab-in-ipilimumab-na%C3%A3-ve-patients-with-advanced-melanoma-in-the-united-states
#19
Jingshu Wang, Bartosz Chmielowski, James Pellissier, Ruifeng Xu, Kendall Stevinson, Frank Xiaoqing Liu
BACKGROUND: Recent clinical trials have shown that pembrolizumab significantly prolonged progression-free survival and overall survival compared with ipilimumab in ipilimumab-naïve patients with unresectable or metastatic melanoma. However, there has been no published evidence on the cost-effectiveness of pembrolizumab for this indication. OBJECTIVE: To assess the long-term cost-effectiveness of pembrolizumab versus ipilimumab in ipilimumab-naïve patients with unresectable or meta-static melanoma from a U...
February 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28121506/ipilimumab-adjuvant-therapy-in-melanoma
#20
LETTER
Alexander M M Eggermont, Stefan Suciu, Alessandro Testori
No abstract text is available yet for this article.
26, 2017: New England Journal of Medicine
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