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https://www.readbyqxmd.com/read/28550712/combined-immune-checkpoint-blockade-anti-pd-1-anti-ctla-4-evaluation-and-management-of-adverse-drug-reactions
#1
REVIEW
Jessica C Hassel, Lucie Heinzerling, Jens Aberle, Oliver Bähr, Thomas K Eigentler, Marc-Oliver Grimm, Victor Grünwald, Jan Leipe, Niels Reinmuth, Julia K Tietze, Jörg Trojan, Lisa Zimmer, Ralf Gutzmer
Combined immune checkpoint blockade (ICB) provides unprecedented efficacy gains in numerous cancer indications, with PD-1 inhibitor nivolumab plus CTLA-4 inhibitor ipilimumab in advanced melanoma as first-ever approved therapies for combined ICB. However, gains in efficacy must be balanced against a higher frequency and severity of adverse drug reactions (ADR). Because delays in diagnosis and management might result in symptom worsening and further complications, clinicians shall be well trained to identify ADR promptly and monitor patients adequately...
May 18, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#2
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28536740/-nivolumab-combined-with-ipilimumab-versus-sunitinib-monotherapy-sunniforecast-an-41-16-of-the-auo-a-phase-2-randomized-open-label-study-in-subjects-with-previously-untreated-and-advanced-unresectable-or-metastatic-non-clear-cell-renal-cell-carcinoma
#3
https://www.readbyqxmd.com/read/28530525/cost-effectiveness-of-nivolumab-ipilimumab-combination-therapy-compared-with-monotherapy-for-first-line-treatment-of-metastatic-melanoma-in-the-united-states
#4
Anna Oh, Dang M Tran, Leann C McDowell, Dor Keyvani, Jay Andrew Barcelon, Oscar Merino, Leslie Wilson
BACKGROUND: The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients. OBJECTIVE: To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#5
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28525897/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#6
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28499411/paraneoplastic-acral-vascular-syndrome-in-a-patient-with-metastatic-melanoma-under-immune-checkpoint-blockade
#7
Thilo Gambichler, Stefanie Strutzmann, Andrea Tannapfel, Laura Susok
BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested. CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla...
May 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28495807/neurologic-serious-adverse-events-associated-with-nivolumab-plus-ipilimumab-or-nivolumab-alone-in-advanced-melanoma-including-a-case-series-of-encephalitis
#8
James Larkin, Bartosz Chmielowski, Christopher D Lao, F Stephen Hodi, William Sharfman, Jeffrey Weber, Karijn P M Suijkerbuijk, Sergio Azevedo, Hewei Li, Daniel Reshef, Alexandre Avila, David A Reardon
BACKGROUND: Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune-related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life-threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment-related encephalitis, and provide practical guidance on diagnosis and management...
May 11, 2017: Oncologist
https://www.readbyqxmd.com/read/28489616/complete-response-to-anti-pd-1-nivolumab-in-massive-skin-metastasis-from-melanoma-efficacy-and-tolerability-in-an-elderly-patient
#9
Andrea Sponghini, Federica Patrucco, Roberto Giorgione, Pamela Farinelli, Francesca Zottarelli, David Rondonotti, Paola Savoia
The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma. The 30-40% of treated patients experience an objective tumour regression, with a significantly prolonged survival and an improved quality of life. Here, we report a case of a 75-year-old Caucasian woman affected by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced multiple relapses after surgery and repeated electrochemotherapy treatments...
May 9, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28458865/primary-anorectal-melanoma-a-rare-entity-case-report
#10
Konstantinos Kothonidis, Fadi Maassarani, Yves Couvreur, Bernard Vanhoute, Robert De Keuleneer
Anorectal melanoma is a rare disorder. There have only been a few cases reported and there is no consensus of treatment. We report a case of 50-year-old Caucasian man presenting intermittent prolapse of an anorectal mass during 6 months with occasional bleeding. Biopsies came up with the diagnosis of malignant melanoma. No distant metastases were found. He underwent an abdominoperineal resection due to internal sphincter invasion. A second tumour was diagnosed in final histologic examination: a dysplastic rectal polyp invaded by the melanoma (collision tumour)...
March 2017: Journal of Surgical Case Reports
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#11
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28436601/management-of-skin-adverse-events-associated-with-immune-checkpoint-inhibitors-in-patients-with-melanoma-a-nursing-perspective
#12
Melissa Thebeau, Krista Rubin, Matthias Hofmann, Julia Grimm, Alyona Weinstein, Jennifer N Choi
PURPOSE: Immune checkpoint inhibitors are associated with a unique immune-related side effect profile that requires prompt recognition and management. Skin toxicities are the most common, and often earliest occurring, drug-related adverse events (AEs) of any grade observed upon treatment with these agents. The purpose of this review is to provide practical guidance on the identification and treatment of skin AEs associated with the immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab) from a nursing perspective, and demonstrate hands-on application of the guidance using relevant patient case studies...
May 2017: Journal of the American Association of Nurse Practitioners
https://www.readbyqxmd.com/read/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#13
REVIEW
Jacek Mackiewicz, Andrzej Mackiewicz
The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28430376/acute-generalized-exanthematous-pustulosis-associated-with-ipilimumab-and-nivolumab
#14
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/28426103/neurotoxicity-from-immune-checkpoint-inhibition-in-the-treatment-of-melanoma-a-single-centre-experience-and-review-of-the-literature
#15
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
#16
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/28417343/adjuvant-therapy-for-melanoma
#17
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/28403786/immune-checkpoint-inhibitors-and-cardiac-toxicity-an-emerging-issue
#18
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/28387097/-new-paradigms-and-metaphors-in-cutaneous-melanoma-treatment
#19
REVIEW
G E Piérard, J L Nizet, P Humbert
In recent years, new drugs have been designed for treating advanced cutaneous malignant melanoma, in particular the metastases. They afford modest benefits despite the fact they are commonly heralded as breakthroughs in the lay press and by some medical opinion leaders. Unfortunately, the use of inflated descriptors of the drug efficacy leads to misunderstandings among the clinicians in charge of patients. Currently, vemurafenib, ipilimumab, pembrolizumab and nivolumab have demonstrated their relative activity in the control of advanced malignant melanoma...
December 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28383639/immune-checkpoint-inhibitors-in-advanced-renal-cell-carcinoma-experience-to-date-and-future-directions
#20
M B Atkins, J I Clark, D I Quinn
In recent years, there has been dramatic expansion of the treatment armamentarium for patients with advanced renal cell carcinoma (aRCC), including drugs targeting vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. Despite these advances, patient outcomes remain suboptimal, underscoring the need for therapeutic interventions with novel mechanisms of action. The advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment landscape for several solid malignancies...
April 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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