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Ipilimumab

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https://www.readbyqxmd.com/read/29344476/acute-angle-closure-precipitated-by-hemorrhage-and-necrosis-of-a-large-uveal-melanoma-in-the-setting-of-systemic-immunomodulatory-therapy
#1
Chau M Pham, Krishna Kalyam, Bradley T Smith, Justin Floyd, John B Holds
Management of nonmetastatic uveal melanoma has been well studied and a large body of work has been published by the Collaborative Ocular Melanoma Study (amongst many others). Management of uveal melanoma that is found to be metastatic upon initial diagnosis, however, is less well defined. We report an interesting case of acute angle closure caused by necrosis and hemorrhage into a large uveal melanoma occurring shortly after initiation of immunomodulatory therapy with ipilimumab and nivolumab for metastatic disease...
November 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/29343970/a-retrospective-examination-of-the-us-food-and-drug-administration-s-clinical-pharmacology-reviews-of-oncology-biologics-for-potential-use-of-therapeutic-drug-monitoring
#2
Brett Fleisher, Sihem Ait-Oudhia
Background: Biologics have gained traction for use in oncology, but have demonstrate clinical variability for efficacy and safety. Therapeutic drug monitoring (TDM) can benefit patients' outcomes from a biologic therapy when the latter has a defined therapeutic window. A clinically relevant therapeutic window may exist for biologics with established exposure-response (E-R) relationships for efficacy and/or safety and a documented maximum tolerated dose (MTD). Additionally, the inter-individual variability (IIV) on the clearance (CL) parameter could determine risks for patients falling outside the proposed therapeutic window...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29341936/rheumatic-manifestations-among-cancer-patients-treated-with-immune-checkpoint-inhibitors
#3
REVIEW
Merav Lidar, Eitan Giat, Daniela Garelick, Yuval Horowitz, Howard Amital, Yael Steinberg-Silman, Jacob Shachter, Ronnie Shapira-Frommer, Gal Markel
BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. Aim To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts...
January 13, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29339377/robust-antitumor-responses-result-from-local-chemotherapy-and-ctla-4-blockade
#4
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339141/-immunotherapy-in-renal-cell-carcinoma-a-booming-clinical-research
#5
N Baize, P Bigot
CONTEXT: Nivolumab, an anti-PD1 immune control point inhibitor, is the first treatment that has improved the overall survival of patients after first-line metastatic renal cell carcinoma in 2015. Over the past two years, a large number of trials on these treatments and the interest of associations are being evaluated. OBJECTIVE: In this article, we propose to summarize the clinical development of checkpoint inhibitors to assess the direction of clinical research in this area...
January 12, 2018: Progrès en Urologie
https://www.readbyqxmd.com/read/29337638/patients-with-advanced-melanoma-who-discontinued-treatment-with-nivolumab-and-ipilimumab-as-a-result-of-adverse-events-lived-significantly-longer-than-patients-who-continued-treatment
#6
Miki Horiguchi, Hajime Uno, Lee-Jen Wei
No abstract text is available yet for this article.
January 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29336315/a-high-neutrophil-to-lymphocyte-ratio-prior-to-braf-inhibitor-treatment-is-a-predictor-of-poor-progression-free-survival-in-patients-with-metastatic-melanoma
#7
Antoine Finon, Julia Zaragoza, Hervé Maillard, Nathalie Beneton, Guido Bens, Mahtab Samimi, Agnès Caille, Laurent Machet
Some studies have shown that a high neutrophil/lymphocyte ratio (NLR) ≥4 before initiating ipilimumab treatment is an independent prognostic indicator of poor survival in patients with metastatic melanoma (MM). To determine whether the NLR before starting BRAF inhibitor (BRAFi) treatment in patients with (MM) is associated with progression-free survival (PFS). This retrospective study included 49 patients consecutively receiving BRAFi for MM between July 2012 and December 2014. Cox proportional hazards regression was used to analyse the relationship between NLR and other factors, such as lactate dehydrogenase (LDH), performance status, BRAFi as first- or second-line therapy, and corticosteroid intake with PFS...
January 16, 2018: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29332608/concealed-complete-response-in-melanoma-patients-under-therapy-with-immune-checkpoint-inhibitors-two-case-reports
#8
Stefan Schliep, Abbas Agaimy, Alexander Cavallaro, Franklin Kiesewetter, Gerold Schuler, Lucie Heinzerling
BACKGROUND: The assessment of tumor size by RECIST using CT scans and MRIs is considered to be standard of care for staging cancer patients. Despite radiologic evidence of widespread disease, we document for the first time that patients were completely free of viable tumor. CASE PRESENTATION: Two patients with metastatic melanoma were treated with immune checkpoint inhibitors (ipilimumab/ nivolumab) and progressive metastases were detected on CT-scans performed shortly before histologic examinations...
January 15, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29328782/the-role-of-nivolumab-in-melanoma
#9
Fabio Gomes, Patricio Serra-Bellver, Paul Lorigan
The incidence of melanoma continues to rise worldwide. Prior to 2010, there had been no progress in the treatment of advanced melanoma in living memory. Since then, immunotherapy has become a standard of care in the treatment of advanced melanoma. Nivolumab is a fully human monoclonal antibody against PD-1, which is a negative regulatory checkpoint in the T cells. The clinical benefit of nivolumab as a single agent is well established, with response rates of ≥40%, durable responses and a favorable tolerability profile...
January 12, 2018: Future Oncology
https://www.readbyqxmd.com/read/29310385/risk-of-gastrointestinal-toxicities-with-pd-1-inhibitors-in-cancer-patients-a-meta-analysis-of-randomized-clinical-trials
#10
Wei Wei, Zhibin Luo
BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibodies have demonstrated significant clinical activity in many cancer entities. Gastrointestinal toxicities are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, the purpose of this study was to evaluate the incidence and risk of gastrointestinal toxicities with PD-1 inhibitors in cancer patients through a meta-analysis. METHODS: Eligible studies were searched for in PubMed, Embase, and the Cochrane Library...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29309091/toxic-injury-to-the-gastrointestinal-tract-after-ipilimumab-therapy-for-advanced-melanoma
#11
Benjamin Shepard, Carrie Trower, Scott Hendrickson
Ipilimumab, cytotoxic T-lymphocyte-associated protein 4-blocking antibody, is known to precipitate tissue-specific immune-related adverse events. The second most common site for immune-related adverse events is the gastrointestinal tract, with toxic injury resulting in diarrhea, colitis, and enterocolitis. In the present case, a woman who received ipilimumab 2 weeks prior was found to have severe, diffuse corticosteroid-refractory gastrointestinal tract toxic injury affecting the stomach, small bowel, and colon...
January 1, 2018: Journal of the American Osteopathic Association
https://www.readbyqxmd.com/read/29308329/assessment-of-neuronal-autoantibodies-in-patients-with-small-cell-lung-cancer-treated-with-chemotherapy-with-or-without-ipilimumab
#12
M Hardy-Werbin, O Arpí, A Taus, P Rocha, D Joseph-Pietras, L Nolan, S Danson, R Griffiths, M Lopez-Botet, A Rovira, J Albanell, C H Ottensmeier, E Arriola
Small-cell lung cancer (SCLC) is often associated with paraneoplastic syndromes. To assess the role of anti-neuronal autoantibodies (NAAs) as biomarkers of treatment outcome, we assessed NAAs in serial samples from SCLC patients treated with chemoimmunotherapy compared to chemotherapy alone. We evaluated 2 cohorts: in cohort 1 (C1), 47 patients received standard platinum/etoposide, and in cohort 2 (C2), 38 patients received ipilimumab, carboplatin and etoposide. Serum samples at baseline and subsequent time points were analyzed for the presence of NAAs...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308314/serum-exosomes-as-predictors-of-clinical-response-to-ipilimumab-in-metastatic-melanoma
#13
Marco Tucci, Anna Passarelli, Francesco Mannavola, Luigia Stefania Stucci, Paolo Antonio Ascierto, Marilena Capone, Gabriele Madonna, Patrizia Lopalco, Francesco Silvestris
Immunotherapy is effective in metastatic melanoma (MM) but most studies failed in discovering a biomarker predictive of clinical response. Exosomes (Exo) from melanoma cells are detectable in sera of MM patients similarly to those produced by immune cells that control the tumor progression. Here, we investigated by flow-cytometry the levels of Exo from both T-cells and dendritic cells (DCs) in 59 patients with MM treated with IPI and the relative expression of PD-1, CD28 and ICOS as well as CD80 and CD86. We found a significant increment of PD-1 and CD28 expression in patients achieving a clinical response reflected by improvement of both PFS and OS...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29306769/phase-ii-trial-of-ipilimumab-in-melanoma-patients-with-preexisting-humoural-immune-response-to-ny-eso-1
#14
G M Haag, I Zoernig, J C Hassel, N Halama, J Dick, N Lang, L Podola, J Funk, C Ziegelmeier, S Juenger, M Bucur, L Umansky, C S Falk, A Freitag, I Karapanagiotou-Schenkel, P Beckhove, A Enk, D Jaeger
BACKGROUND: Immune checkpoint therapy has dramatically changed treatment options in patients with metastatic melanoma. However, a relevant part of patients still does not respond to treatment. Data regarding the prognostic or predictive significance of preexisting immune responses against tumour antigens are conflicting. Retrospective data suggested a higher clinical benefit of ipilimumab in melanoma patients with preexisting NY-ESO-1-specific immunity. PATIENTS AND METHODS: Twenty-five patients with previously untreated or treated metastatic melanoma and preexisting humoural immune response against NY-ESO-1 received ipilimumab at a dose of 10 mg/kg in week 1, 4, 7, 10 followed by 3-month maintenance treatment for a maximum of 48 weeks...
January 4, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29303446/combination-ipilimumab-and-radiosurgery-for-brain-metastases-tumor-edema-and-adverse-radiation-effects
#15
Kevin Diao, Shelly X Bian, David M Routman, Cheng Yu, Paul E Kim, Naveed A Wagle, Michael K Wong, Gabriel Zada, Eric L Chang
OBJECTIVE Tumor and edema volume changes of brain metastases after stereotactic radiosurgery (SRS) and ipilimumab are not well described, and there is concern regarding the safety of combination treatment. The authors evaluated tumor, edema, and adverse radiation-induced changes after SRS with and without ipilimumab and identified associated risk factors. METHODS This single-institution retrospective study included 72 patients with melanoma brain metastases treated consecutively with upfront SRS from 2006 to 2015...
January 5, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29285547/association-of-immunotherapy-with-durable-survival-as-defined-by-value-frameworks-for-cancer-care
#16
Omer Ben-Aharon, Racheli Magnezi, Moshe Leshno, Daniel A Goldstein
Importance: Modern immuno-oncology agents have generated great excitement because of their potential to provide durable survival for some patients. However, there is concern regarding the cost of cancer care, and multiple frameworks have been developed to assess value. The American Society of Clinical Oncology (ASCO) framework awards bonus points if substantial durable survival is demonstrated. Objective: To assess whether modern immuno-oncology agents reach defined efficacy thresholds in value frameworks...
December 28, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29284380/potential-cost-savings-by-dose-down-rounding-of-monoclonal-antibodies-in-a-community-cancer-center
#17
Mehmet S Copur, Curtis Gnewuch, Megan Schriner, Mark Tharnish, Mithat Gonen, Monica McDonald, Jami Kezeor, Ryan C Ramaekers, Dron Gauchan, Douglas Clark, Lois Greenwalt, Mary Mickey, Max Norvell
Purpose Increasing new cancer cases and approval of effective but expensive new drugs extending survival have led to unsustainable cancer care costs. Potential cost savings by a hypothetical dose down-rounding project of monoclonal antibodies at a community-based cancer center is presented. Methods From October 2014 through October 2015, metastatic cancer patients receiving monoclonal antibodies at CHI-Health St Francis Cancer Treatment Center in Grand Island, Nebraska, were identified through electronic health records...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29283791/durable-complete-response-after-discontinuation-of-pembrolizumab-in-patients-with-metastatic-melanoma
#18
Caroline Robert, Antoni Ribas, Omid Hamid, Adil Daud, Jedd D Wolchok, Anthony M Joshua, Wen-Jen Hwu, Jeffrey S Weber, Tara C Gangadhar, Richard W Joseph, Roxana Dronca, Amita Patnaik, Hassane Zarour, Richard Kefford, Peter Hersey, Jin Zhang, James Anderson, Scott J Diede, Scot Ebbinghaus, F Stephen Hodi
Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab...
December 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29279030/case-report-of-ipilimumab-induced-diffuse-nonnecrotizing-granulomatous-lymphadenitis-and-granulomatous-vasculitis
#19
Kari Arellano, James C Mosley, Donald C Moore
Ipilimumab is indicated for the treatment of melanoma in both the metastatic and adjuvant setting. Ipilimumab inhibits cytotoxic T-lymphocyte antigen 4, leading to the augmentation of T-cell activity and an antitumor immune system response. The side effect profile of ipilimumab consists of autoimmune-like events such as dermatitis, colitis, and thyroiditis. These immune-related adverse events can be serious, often resulting in the need for systemic immunosuppression with corticosteroids. We present a case of diffuse, nonnecrotizing granulomatous lymphadenitis and granulomatous vasculitis in a heavily pretreated patient with metastatic melanoma...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29275461/tumor-immuno-environment-in-cancer-progression-and-therapy
#20
Pawel Kalinski, James E Talmadge
The approvals of Provenge (Sipuleucel-T), Ipilimumab (Yervoy/anti-CTLA-4) and blockers of the PD-1 - PD-L1/PD-L2 pathway, such as nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq), have established immunotherapy as a key component of comprehensive cancer care. Further, murine mechanistic studies and studies in immunocompromised patients have documented the critical role of immunity in effectiveness of radio- and chemotherapy. However, in addition to the ability of the immune system to control cancer progression, it can also promote tumor growth, via regulatory T cells (Tregs), myeloid-derived dendritic cells (MDSCs) and tumor associated macrophages (TAM), which can enhance survival of cancer cells directly or via the regulation of the tumor stroma...
2017: Advances in Experimental Medicine and Biology
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