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Ipilimumab

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https://www.readbyqxmd.com/read/27920706/ipilimumab-induced-enteritis-without-colitis-a-new-challenge
#1
Marcus Messmer, Sunita Upreti, Yaman Tarabishy, Nikhilesh Mazumder, Reezwana Chowdhury, Mark Yarchoan, Matthias Holdhoff
INTRODUCTION: Ipilimumab is an immune checkpoint inhibitor targeting cytotoxic T-lymphocyte associated antigen 4 (CTLA4), approved to treat metastatic melanoma. It was the first therapy shown to prolong survival in a large, randomized clinical trial. However, immune-related adverse events are common and can be severe. Enterocolitis is a common adverse event with ipilimumab, but enteritis without colitis has not been previously described. CASE REPORT: An 83-year-old man presented to our hospital with grade 3 diarrhea for 5 days...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920696/sequential-therapy-with-nivolumab-followed-by-ipilimumab-induces-complete-response-in-metastatic-melanoma-of-the-lung-but-with-severe-hepatotoxicities
#2
Sadanori Furudate, Taku Fujimura, Yumi Kambayashi, Takanori Hidaka, Akira Hashimoto, Setsuya Aiba
Since nivolumab significantly prolongs survival in patients with metastatic melanoma, the number of patients administered nivolumab is increasing, but only 30-40% of patients who received nivolumab monotherapy experienced objective tumor regression. Therefore, enhancing its anti-tumor immune response is of great interest to dermato-oncologists. In this report, we present a case of multiple metastatic melanomas in the lung successfully treated with nivolumab (2 mg/kg every 3 weeks for 12 weeks) followed by ipilimumab (3 mg/kg every 3 weeks for 9 weeks), but with severe liver dysfunction...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27919707/autoimmune-cardiotoxicity-of-cancer-immunotherapy
#3
Feixiong Cheng, Joseph Loscalzo
Contemporary immunotherapies (e.g., immune checkpoint inhibitors), which enhance the immune response to cancer cells, improve clinical outcomes in several malignancies. A recent study reported the cases of two patients with metastatic melanoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; these examples highlight the risk of unbridled activation of the immune system.
December 2, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#4
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27914096/successful-treatment-of-multiple-in-transit-melanomas-on-the-leg-with-intensity-modulated-radiotherapy-and-immune-checkpoint-inhibitors-report-of-two-cases
#5
Taku Fujimura, Yumi Kambayashi, Sadanori Furudate, Takanori Hidaka, Yota Sato, Kayo Tanita, Hisayuki Tono, Akira Tsukada, Akira Hashimoto, Setsuya Aiba
Because the efficacy rates of monotherapy with immune checkpoint inhibitors such as nivolumab or ipilimumab are not sufficient, to enhance the antitumor effects of these reagents is of great interest among dermato-oncologists. In this report, we describe two cases of multiple in-transit metastatic melanomas on the leg successfully treated with intensity-modulated radiotherapy (IMRT) using a CyberKnife in combination with ipilimumab or nivolumab. Our cases suggested that IMRT could enhance the antitumor effects of immune checkpoint inhibitors in patients with multiple in-transit melanomas...
December 3, 2016: Journal of Dermatology
https://www.readbyqxmd.com/read/27911979/clinicopathological-features-and-clinical-outcomes-associated-with-tp53-and-braf-n-on-v-600-mutations-in-cutaneous-melanoma-patients
#6
Dae Won Kim, Lauren E Haydu, Aron Y Joon, Roland L Bassett, Alan E Siroy, Michael T Tetzlaff, Mark J Routbort, Rodabe N Amaria, Jennifer A Wargo, Jennifer L McQuade, Jan Kemnade, Patrick Hwu, Scott E Woodman, Jason Roszik, Kevin B Kim, Jeffrey E Gershenwald, Alexander J Lazar, Michael A Davies
BACKGROUND: BRAF(V600) , NRAS, TP53, and BRAF(Non-V600) are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF(V600) and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF(Non-V600) mutations. METHODS: This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926)...
December 2, 2016: Cancer
https://www.readbyqxmd.com/read/27905824/improved-survival-and-complete-response-rates-in-patients-with-advanced-melanoma-treated-with-concurrent-ipilimumab-and-radiotherapy-versus-ipilimumab-alone
#7
Kristian M Koller, Heath B Mackley, Jason Liu, Henry Wagner, Giampaolo Talamo, Todd D Schell, Colette Pameijer, Rogerio I Neves, Bryan Anderson, Kathleen M Kokolus, Carol A Mallon, Joseph J Drabick
There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not...
December 1, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27894673/treatment-related-death-in-cancer-patients-treated-with-immune-checkpoint-inhibitors-a-systematic-review-and-meta-analysis
#8
O Abdel-Rahman, D Helbling, J Schmidt, U Petrausch, A Giryes, A Mehrabi, O Schöb, M Mannhart, H Oweira
AIMS: We carried out a meta-analysis to determine the risk of treatment-related death associated with immune checkpoint inhibitor use in cancer patients. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, pembrolizumab; nivolumab; tremelimumab and atezolizumab...
November 25, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/27892653/low-baseline-levels-of-nk-cells-may-predict-a-positive-response-to-ipilimumab-in-melanoma-therapy
#9
Julia K Tietze, Daniela Angelova, Markus V Heppt, Thomas Ruzicka, Carola Berking
The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T cell populations has been studied extensively but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56(dim) and CD56(bright) NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27882779/ipilimumab-from-preclinical-development-to-future-clinical-perspectives-in-melanoma
#10
Paul Letendre, Varun Monga, Mohammed Milhem, Yousef Zakharia
The arsenal for the treatment of metastatic melanoma is limited. A new approach to therapy using checkpoint blockade has improved overall survival in this patient population. Ipilimumab a CTLA-4 monoclonal antibody is a first in class drug that has pioneered this revolution. In this review, the authors provide an account of the different stages that led to the development of ipilimumab, its approval in the clinical setting for the treatment of advanced melanoma and ongoing investigations of combinatorial immune therapy...
November 24, 2016: Future Oncology
https://www.readbyqxmd.com/read/27881588/glucocorticoids-did-not-reverse-type-1-diabetes-mellitus-secondary-to-pembrolizumab-in-a-patient-with-metastatic-melanoma
#11
Jasna Aleksova, Peter K H Lau, Georgia Soldatos, Grant McArthur
Immune checkpoint inhibitors offer patients with advanced melanoma substantial improvements in survival. Unlike chemotherapy, immune checkpoint inhibitors such as ipilimumab and pembrolizumab cause unique immune-related adverse events (irAEs), including the development of endocrinopathies. We report a case of a man aged 60 years who developed diabetic ketoacidosis (DKA) following the use of pembrolizumab for the treatment of metastatic melanoma. He received four cycles of ipilimumab, before proceeding to pembrolizumab...
November 23, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27878363/improvement-of-overall-survival-in-stage-iv-melanoma-patients-during-2011-2014-analysis-of-real-world-data-in-441-patients-of-the-german-central-malignant-melanoma-registry-cmmr
#12
Andrea Forschner, Felizitas Eichner, Teresa Amaral, Ulrike Keim, Claus Garbe, Thomas Kurt Eigentler
BACKGROUND: During 2011 and 2014, new treatment modalities like tyrosine kinase inhibitors and checkpoint inhibitors were introduced into the therapy of metastatic melanoma. This study addresses the question whether overall survival (OS) of metastatic melanoma patients has already been improved in 441 patients diagnosed with metastatic melanoma between 2011 and 2014 in the real-world setting at the University Hospital Tuebingen. METHODS: All patients were documented with their different therapies by the CMMR and followed up until March 2016...
November 22, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27873302/ultrasonographic-findings-can-identify-pseudoprogression-under-nivolumab-therapy
#13
K Imafuku, H Hata, S Kitamura, T Yanagi, H Shimizu
'Pseudoprogression' is often seen in patients with melanomas who are treated with immune-checkpoint inhibitors such as nivolumab or ipilimumab. We sometimes evaluate metastatic lesions by imaging tests such as CT or PET-CT. 'Pseudoprogression' usually occurs upon the initial administration, which may make it difficult for the physician to determine the disease condition. In our two cases of metastatic melanoma treated with nivolumab (anti-PD-1 antibody), we examined the ultrasonography (US) of target lesions that could be accessed from the body surface, such as those of the regional lymph node or subcutaneous metastasis...
November 22, 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/27864228/ifn%C3%AE-mutations-prompt-ctla-4-inhibitor-resistance
#14
(no author information available yet)
A recent study pinpoints loss of IFNγ signaling as one reason why many patients do not respond to the CTLA-4 inhibitor ipilimumab. Analyzing whole-exome tumor sequencing data from 16 patients with melanoma, the researchers found multiple copy-number alterations that led to the loss of key IFNγ pathway genes in 12 ipilimumab nonresponders. Mice bearing melanoma tumors that lacked one of these genes, IFNGR1, also had an impaired response to anti-CTLA-4 therapy and significantly reduced overall survival, compared with their counterparts whose tumors had intact IFNGR1...
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27863186/model-based-characterization-of-the-pharmacokinetics-of-pembrolizumab-a-humanized-anti-pd-1-monoclonal-antibody-in-advanced-solid-tumors
#15
M Ahamadi, T Freshwater, M Prohn, C H Li, D P de Alwis, R de Greef, J Elassaiss-Schaap, A Kondic, J A Stone
Pembrolizumab, a potent antibody against programmed death 1 (PD-1) receptor, has shown robust antitumor activity and manageable safety in patients with advanced solid tumors. Its pharmacokinetic (PK) properties were analyzed with population PK modeling using pooled data from the KEYNOTE-001, -002, and -006 studies of patients with advanced melanoma, non-small cell lung cancer (NSCLC), and other solid tumor types. Pembrolizumab clearance was low and the volume of distribution small, as is typical for therapeutic antibodies...
November 14, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27861630/correction-preclinical-development-of-ipilimumab-and-nivolumab-combination-immunotherapy-mouse-tumor-models-in-vitro-functional-studies-and-cynomolgus-macaque-toxicology
#16
Mark J Selby, John J Engelhardt, Robert J Johnston, Li-Sheng Lu, Minhua Han, Kent Thudium, Dapeng Yao, Michael Quigley, Jose Valle, Changyu Wang, Bing Chen, Pina M Cardarelli, Diann Blanset, Alan J Korman
[This corrects the article DOI: 10.1371/journal.pone.0161779.].
2016: PloS One
https://www.readbyqxmd.com/read/27857838/hyponatraemia-secondary-to-nivolumab-induced-primary-adrenal-failure
#17
Harris Trainer, Paul Hulse, Claire E Higham, Peter Trainer, Paul Lorigan
: Checkpoint inhibitors, such as ipilimumab and pembrolizumab, have transformed the prognosis for patients with advanced malignant melanoma and squamous non-small-cell lung cancer, and their use will only expand as experience is gained in a variety of other malignancies, for instance, renal and lymphoma. As the use of checkpoint inhibitors increases, so too will the incidence of their unique side effects, termed immune-related adverse events (irAEs), which can affect dermatological, gastrointestinal, hepatic, endocrine and other systems...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27845904/the-evaluation-of-immunotherapy-and-chemotherapy-treatment-on-melanoma-a-network-meta-analysis
#18
BaSang CiRen, Xinhua Wang, Ziwen Long
BACKGROUND: Melanoma is a highly malignant tumor that develops from a neural crest derivative called melanocytes. Chemotherapy is recommended for patients with stage III/IV melanoma. Immunomodulation has also been shown to effectively improve the survival rate of such patients. In the current study, we aimed to perform a network meta-analysis on the therapeutic value of chemotherapy and immunotherapy on melanoma. RESULTS: Twenty randomized controlled trials (RCTs) were enrolled in the study...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27843587/life-threatening-colitis-and-complete-response-with-ipilimumab-in-a-patient-with-metastatic-braf-mutant-melanoma-and-rheumatoid-arthritis
#19
Francisco Aya, Lydia Gaba, Ivan Victoria, Aranzazu Fernandez-Martinez, Virginia Ruiz-Esquide, Estela Pineda, Monica Tosca, Margarita Viladot, Veronica Pereira, Josep Malvehy, Aleix Prat, Ana Arance
Immune checkpoint inhibitors, such as ipilimumab (an anti-CTLA4 antibody), have become a commonly used therapy in cancer. To date, safety data of patients with underlying autoimmune disease is limited. We present a case of a patient with rheumatoid arthritis who was diagnosed of a BRAF-mutant metastatic melanoma. The patient was treated with ipilimumab and presented with high-grade colitis requiring immunosuppressors. Despite of the immune-related adverse event, no exacerbation of the rheumatoid arthritis was observed and the patient achieved a complete response...
2016: ESMO Open
https://www.readbyqxmd.com/read/27842767/drug-hepatotoxicity-newer-agents
#20
REVIEW
Chalermrat Bunchorntavakul, K Rajender Reddy
Idiosyncratic hepatotoxicity is one of the most common reasons for an approved drug being restricted. This article focuses on hepatotoxicity of selected and recently introduced agents, such as, tyrosine kinase inhibitors, monoclonal antibodies, novel oral anticoagulants, newer antiplatelets, antibiotics, anti-diabetics, anti-epileptics, anti-depressants, anti-psychotics and anti-retrovirals. Overall, the incidence of clinically relevant hepatotoxicity from newer agents seems to be lower than that of the older agents...
February 2017: Clinics in Liver Disease
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