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Ipilimumab

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https://www.readbyqxmd.com/read/28430376/acute-generalized-exanthematous-pustulosis-associated-with-ipilimumab-and-nivolumab
#1
Basile Page, Luca G Borradori, Helmut Beltraminelli, Nikhil Yawalkar, Robert E Hunger
Acute generalized exanthematous pustulosis (AGEP) is a rare potentially severe adverse cutaneous eruption, that is usually induced by a variety of drugs, most commonly anti-bacterial drugs. AGEP is characterized by the acute development of extensive, non-follicular, sterile pustules on an erythematous background accompanied by systemic symptoms such as fever and leucocytosis.¹ The prognosis is usually favourable, but in elderly patients with comorbidities morbidity and mortality are increased.² This article is protected by copyright...
April 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#2
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428880/long-term-complete-remission-with-ipilimumab-in-metastatic-castrate-resistant-prostate-cancer-case-report-of-two-patients
#3
Luc Cabel, Elika Loir, Gwenaelle Gravis, Pernelle Lavaud, Christophe Massard, Laurence Albiges, Giulia Baciarello, Yohann Loriot, Karim Fizazi
BACKGROUND: Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28426103/neurotoxicity-from-immune-checkpoint-inhibition-in-the-treatment-of-melanoma-a-single-centre-experience-and-review-of-the-literature
#4
L Spain, G Walls, M Julve, K O'Meara, T Schmid, E Kalaitzaki, S Turajlic, M Gore, J Rees, J Larkin
Background: Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase III trials. Immune-related neurological toxicity of varying severity has been reported in the literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab and pembrolizumab is reported as <1% in published clinical trials. We aimed to identify the incidence of neurotoxicity in our institution across anti-CTLA4 and anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425751/development-of-red-blood-cell-autoantibodies-following-treatment-with-checkpoint-inhibitors-a-new-class-of-anti-neoplastic-immunotherapeutic-agents-associated-with-immune-dysregulation
#5
Laura L Cooling, John Sherbeck, Jonathon C Mowers, Sheri L Hugan
Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28423678/influence-of-ipilimumab-on-expanded-tumour-derived-t-cells-from-patients-with-metastatic-melanoma
#6
Jon Bjoern, Rikke Lyngaa, Rikke Andersen, Lisbet Hölmich Rosenkrantz, Sine Reker Hadrup, Marco Donia, Inge Marie Svane
INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus, we hypothesized that treatment with anti-CTLA-4 antibodies can induce favourable changes to be detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG-3...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423487/ipilimumab-treatment-decreases-monocytic-mdscs-and-increases-cd8-effector-memory-t-cells-in-long-term-survivors-with-advanced-melanoma
#7
Yago Pico de Coaña, Maria Wolodarski, Isabel Poschke, Yuya Yoshimoto, Yuan Yang, Maria Nyström, Ulrika Edbäck, Suzanne Eghyazi Brage, Andreas Lundqvist, Giuseppe V Masucci, Johan Hansson, Rolf Kiessling
Ipilimumab has revolutionized malignant melanoma therapy, but a better understanding of the mechanisms behind treatment response and adverse effects is needed. In this work, the immune system of ipilimumab treated patients was monitored to investigate potential mechanisms of action that may correlate with treatment outcome. Blood samples from 43 advanced melanoma patients were taken before, during and at the end of treatment. Hematological parameters were measured and flow cytometry analysis was performed in fresh samples within two hours of sample collection...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422751/twelve-year-survival-and-immune-correlates-in-dendritic-cell-vaccinated-melanoma-patients
#8
Stefanie Gross, Michael Erdmann, Ina Haendle, Steve Voland, Thomas Berger, Erwin Schultz, Erwin Strasser, Peter Dankerl, Rolf Janka, Stefan Schliep, Lucie Heinzerling, Karl Sotlar, Pierre Coulie, Gerold Schuler, Beatrice Schuler-Thurner
BACKGROUND: Reports on long-term (≥10 years) effects of cancer vaccines are missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous melanoma patients to further explore the immunogenicity of our DC vaccine and to establish its long-term toxicity and clinical benefit after a planned 10-year followup. METHODS: Monocyte-derived DCs matured by TNFα, IL-1β, IL-6, and PGE2 and then loaded with 4 HLA class I and 6 class II-restricted tumor peptides were injected intradermally in high doses over 2 years...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28417343/adjuvant-therapy-for-melanoma
#9
REVIEW
Aya Agha, Ahmad A Tarhini
Systemic adjuvant therapy for surgically resected cutaneous melanoma that is at high risk for disease recurrence and death targets residual micrometastatic disease which is the source of future local or distant relapse. Interferon-alfa (IFNα) has been the most extensively studied in regimens that varied by dosage, route of administration, formulation, and duration of therapy. Most regimens have demonstrated improvements in relapse-free survival (RFS), while the regimen administered at high dosage (HDI) showed improvements in overall survival (OS) in two out of three RCTs...
May 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28417311/immune-checkpoint-inhibitors-for-brain-metastases
#10
REVIEW
Aaron C Tan, Amy B Heimberger, Alexander M Menzies, Nick Pavlakis, Mustafa Khasraw
PURPOSE OF REVIEW: Metastasis of cancer to the brain typically portends a poor prognosis and often results in significant morbidity, including from the side effects of treatment. More effective therapies for patients with brain metastases are needed. The current treatment paradigm uses multiple modalities, including surgery, radiation, and in some contexts, systemic chemotherapy and immunotherapy. Immune checkpoint inhibitors are increasingly being used to treat extracranial disease, and their effectiveness in the management of brain metastases needs to be understood...
June 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28411392/clinical-prognostic-markers-in-stage-iiic-melanoma
#11
Max F Madu, Jaap H H Schopman, Danique M S Berger, Willem M C Klop, Katarzyna Jóźwiak, Michel W J M Wouters, Jos A van der Hage, Alexander C J van Akkooi
BACKGROUND: Although the EORTC 18071-trial has shown a clear survival benefit for adjuvant ipilimumab, accurately selecting patients for this toxic adjuvant therapy is important. We aimed to identify prognostic factors for death and disease recurrence in AJCC stage IIIC melanoma patients. PATIENTS AND METHODS: Retrospective analysis of patients who underwent lymph node dissection (LND) for stage IIIC melanoma in our institution between 2000 and 2016. Baseline characteristics, melanoma-specific survival (MSS), and disease-free survival (DFS) were assessed, and prognostic factors for recurrence and survival were analyzed using uni- and multivariable analysis...
April 15, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28411205/vista-upregulation-may-promote-resistance-to-ctla-4-blockade
#12
(no author information available yet)
CTLA-4 blockade with ipilimumab activates the immune inhibitory VISTA checkpoint in prostate cancer.
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28410286/successful-treatment-with-imatinib-after-nilotinib-and-ipilimumab-in-a-c-kit-mutated-advanced-melanoma-patient-a-case-report
#13
Carla Murer, Pascale Kränzlin-Stieger, Lars E French, Reinhard Dummer, Simone M Goldinger
Treatment of melanoma remains a challenge in advanced disease. Recently, the molecular differentiation in BRAF-mutated, NRAS-mutated and c-kit-mutated melanomas led to new treatment strategies. Different trials show that imatinib or nilotinib lead to meaningful responses in c-kit-mutated melanoma patients. There are little published data on sequential inhibition using these two drugs in melanoma. We describe the sequential use of imatinib after nilotinib in a c-kit-mutated melanoma patient, who progressed on interferon, Allovectin, dacarbazine, nilotinib and ipilimumab, and was finally treated with the c-kit inhibitor imatinib...
April 13, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28408015/accounting-for-cured-patients-in-cost-effectiveness-analysis
#14
Megan Othus, Aasthaa Bansal, Lisel Koepl, Samuel Wagner, Scott Ramsey
BACKGROUND: Economic evaluations often measure an intervention effect with mean overall survival (OS). Emerging types of cancer treatments offer the possibility of being "cured" in that patients can become long-term survivors whose risk of death is the same as that of a disease-free person. Describing cured and noncured patients with one shared mean value may provide a biased assessment of a therapy with a cured proportion. OBJECTIVE: The purpose of this article is to explain how to incorporate the heterogeneity from cured patients into health economic evaluation...
April 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28405510/correlation-between-previous-treatment-with-braf-inhibitors-and-clinical-response-to-pembrolizumab-in-patients-with-advanced-melanoma
#15
Ester Simeone, Antonio Maria Grimaldi, Lucia Festino, Diana Giannarelli, Vito Vanella, Marco Palla, Marcello Curvietto, Assunta Esposito, Giuseppe Palmieri, Nicola Mozzillo, Paolo Antonio Ascierto
The optimal sequencing of targeted treatment and immunotherapy in the treatment of advanced melanoma is a key question and prospective studies to address this are ongoing. Previous observations suggest that treating first with targeted therapy may select for more aggressive disease, meaning that patients may not gain full benefit from subsequent immunotherapy. In a single-center retrospective analysis, we investigated whether response to pembrolizumab was affected by previous BRAF inhibitor therapy. A total of 42 patients with metastatic cutaneous or mucosal melanoma who had received previous treatment with ipilimumab were treated with pembrolizumab as part of the Italian expanded access program...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405509/improved-time-to-disease-progression-in-the-brain-in-patients-with-melanoma-brain-metastases-treated-with-concurrent-delivery-of-radiosurgery-and-ipilimumab
#16
Tijana Skrepnik, Srinath Sundararajan, Haiyan Cui, Baldassarre Stea
Background: To identify the optimal sequencing and timing of immunotherapy (IT) and stereotactic radiosurgery (SRS) for melanoma brain metastases (MBMs). Methods: The elapsed days between IT and SRS were correlated with local control (LC), regional brain control (RBC), time to CNS progression (TTPCNS), overall survival (OS), and radiation necrosis (RN). Logistic regression and Cox proportional models were used for statistical analysis. Results: Twenty-five patients with 58 MBMs underwent SRS and IT. Median follow-up was 22...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403786/immune-checkpoint-inhibitors-and-cardiac-toxicity-an-emerging-issue
#17
Gilda Varricchi, Giancarlo Marone, Valentina Mercurio, Maria Rosaria Galdiero, Domenico Bonaduce, Carlo G Tocchetti
Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Cancer immunotherapies over the last years have revolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis...
April 7, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28401443/prevalence-of-hypophysitis-in-a-cohort-of-patients-with-metastatic-melanoma-and-prostate-cancer-treated-with-ipilimumab
#18
Lucia Brilli, Riccardo Danielli, Cristina Ciuoli, Luana Calabrò, Anna Maria Di Giacomo, Alfonso Cerase, Patrizia Paffetti, Fausta Sestini, Brunetta Porcelli, Michele Maio, Furio Pacini
OBJECTIVE: Ipilimumab is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4, that has been shown to significantly improve survival in patients with metastatic melanoma. Blocking cytotoxic T-lymphocyte antigen-4 elicits T cell activation, proliferation and anti-tumor response, but can also trigger immune-related adverse events. Among immune-related endocrinopathies, hypophysitis represents the most frequent, with an incidence up to 17% in patients treated with ipilimumab...
April 12, 2017: Endocrine
https://www.readbyqxmd.com/read/28398170/ipilimumab-in-real-world-clinical-practice-efficacy-and-safety-data-from-a-multicenter-observational-study
#19
Alberto Russi, Vera Damuzzo, Marco Chiumente, Jacopo Pigozzo, Marco Cesca, Vanna Chiarion-Sileni, Angelo Claudio Palozzo
In patients with metastatic melanoma, ipilimumab has been shown to improve long-term survival. This observational multicenter study reports clinical outcomes of 418 patients treated with second-line ipilimumab from February 2013 to August 2014. Median overall survival (OS) was 6.43 months (95%CI: 5.45-7.42; n = 300), while median progression-free survival (PFS) was 3.7 months (95%CI: 3.23-4.17; n = 188). Demographic factors, such as sex or number of previous therapies did not affect OS. Survival was shorter in patients with ECOG > 0 (Eastern Cooperative Oncology Group, Performance Status) (p < 0...
April 11, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28397508/an-autoimmune-haemolytic-anaemia-secondary-to-ipilimumab-treatment
#20
B Ramos, G Gastal, R K Rovere
BACKGROUND: Melanoma is one of the fastest growing neoplasms worldwide. Treatment of metastatic disease has swiftly shifted in the last decade from generally ineffective chemotherapy regimens to highly effective targeted treatments or immunotherapy, with a range of side effects that differ completely from those of previous treatments for this disease. CASE: We present a case of a 71-year-old man with diagnosis metastatic melanoma. This patient was treated with anti-CTLA-4 antibody ipilimumab...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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