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"nivolumab" and "ipilimumab"

Erik H Middlebrooks, Brian C Westbrook, Robert M Conry
Immune checkpoint blockade (CPB) utilizing such agents as ipilimumab, nivolumab, or pembrolizumab has revolutionized melanoma therapy and has seen continued utilization in numerous other malignancies in recent years. However, these agents come at the price of inflammatory immune-related adverse events. Despite the increasing recognition of biochemical thyroid dysfunction associated with CPB, information regarding potential imaging findings is sparse. We describe the first 2 cases of acute thyroiditis following CPB presenting as diffuse thyromegaly documented by computed tomography, ultrasound, and iodine uptake imaging...
February 2018: Radiology Case Reports
Matthew J Bott, Jonathan Cools-Lartigue, Kay See Tan, Joseph Dycoco, Manjit S Bains, Robert J Downey, James Huang, James M Isbell, Daniela Molena, Bernard J Park, Valerie W Rusch, Smita Sihag, David R Jones, Prasad S Adusumilli
BACKGROUND: Surgeons are increasingly asked to operate on patients with residual disease after immunotherapy. The safety and utility of lung resection in this setting are unknown. METHODS: We performed a retrospective review of patients who underwent lung resection within 6 months of treatment with checkpoint blockade agents for metastatic or unresectable cancer. Survival was estimated from first resection using the Kaplan-Meier approach. RESULTS: Database query identified 19 patients who underwent 22 resections for suspected residual disease with therapeutic intent following immunotherapy between 2012 and 2016...
March 14, 2018: Annals of Thoracic Surgery
Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
Georges Al-Helou, Nardos Temesgen, Jonathan Gwizdala, Jalil Ahari
Our patient is a 69-year-old man who presented to the emergency department with left-sided hemiparesis that started 4 hours prior to presentation. Brain CT showed right basal ganglia and internal capsule haemorrhagic strokes. MRI revealed multiple brain lesions suspicious for metastases. Further workup revealed a 5 cm lung mass and a 1 cm pancreatic nodule. Biopsy of both pulmonary and pancreatic lesions was consistent with melanoma and was similar histologically. The patient underwent cyberknife stereotactic radiosurgery to the brain metastases followed by immunotherapy with pembrolizumab, and then by nivolumab and ipilimumab...
March 15, 2018: BMJ Case Reports
Kevin Zarrabi, Shenhong Wu
BACKGROUND: Nivolumab is approved for the treatment of many cancers. This meta-analysis was conducted to determine the risk of hepatotoxicity with nivolumab therapy. METHODS: An analysis from all phase I-III clinical trials up to December 2016 examining nivolumab was conducted. Data on elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each trial. Incidence and relative risk (RR) were calculated using random- or fixed-effects models with 95% confidence intervals (CIs)...
March 14, 2018: Oncology
Yang Meng, Nadine Hertel, John Ellis, Edith Morais, Helen Johnson, Zoe Philips, Neil Roskell, Andrew Walker, Dawn Lee
BACKGROUND: Nivolumab was the first programmed death receptor 1 (PD-1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients. OBJECTIVE: To evaluate the cost effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. METHODS: A Markov state-transition model was developed to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and versus ipilimumab, dabrafenib, and vemurafenib for BRAF mutation-positive patients...
March 9, 2018: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
Nghi C Nguyen, Melissa K Yee, Abuzar M Tuchayi, John M Kirkwood, Hussein Tawbi, James M Mountz
Introduction: This pilot study aimed at exploring the utility of the proliferation tracer F-18 fluorothymidine (FLT) and positron-emission tomography (PET)/magnetic resonance imaging (MRI) (FLT-PET/MRI) for early treatment monitoring in patients with melanoma brain metastasis (MBM) who undergo targeted therapy or immunotherapy. Material and Methods: Patients with newly diagnosed MBM underwent baseline and follow-up FLT-PET/MRI scans at 3-4 weeks of targeted therapy or immunotherapy...
2018: Frontiers in Oncology
Katjana S Schwab, Glenn Kristiansen, Hans H Schild, Stefanie E A Held, Annkristin Heine, Peter Brossart
Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) are limited, and prognosis is poor. Nivolumab (Opdivo) has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HNSCC who have disease progression on or after platinum-based therapy. Recently, in patients with metastatic malignant melanoma a significant improvement of outcome and response was achieved with the combination of ipilimumab (CTLA4 antibody) and the programmed death (PD)-1 inhibitor nivolumab compared with monotherapy...
January 2018: Case Reports in Oncology
Taku Fujimura, Yumi Kambayashi, Yota Sato, Kayo Tanita, Sadanori Furudate, Akira Tsukada, Hisayuki Tono, Akira Hashimoto, Setsuya Aiba
Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod...
January 2018: Case Reports in Oncology
Akira Utsunomiya, Noritaka Oyama, Shiro Iino, Natsuki Baba, Takenao Chino, Natsuko Utsunomiya, Minoru Hasegawa
Immune checkpoint inhibitors, such as ipilimumab and nivolumab, reverse the imbalance of antitumor self-tolerance and enhance T-cell responses. Currently, ipilimumab and nivolumab have a reported therapeutic impact on unresectable or metastatic melanomas; however, they also induce immune-related adverse events (irAEs). Ipilimumab-induced cutaneous irAEs are mostly low grade and manageable, although all-grade rash may occur in approximately 45% of all patients. We here report the case of a young woman with erythema multiforme major, which developed after sequential use of these 2 immune checkpoint inhibitors for advanced melanoma of the scalp...
January 2018: Case Reports in Dermatology
Florence Gunawan, Elizabeth George, Adam Roberts
Immune checkpoint inhibitors are the mainstay of treatment for advanced melanoma, and their use is being increasingly implicated in the development of autoimmune endocrinopathies. We present a case of a 52-year-old man with metastatic melanoma on combination nivolumab and ipilumimab therapy who developed concurrent hypophysitis, type 1 diabetes mellitus (T1DM) and diabetes insipidus. He presented prior to third cycle of combination treatment with a headache, myalgias and fatigue. Biochemistry and MRI pituitary confirmed anterior pituitary dysfunction with a TSH: 0...
2018: Endocrinology, Diabetes & Metabolism Case Reports
Danielle Benedict Sacdalan, Josephine Anne Lucero, Dennis Lee Sacdalan
Introduction: Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR) is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients...
2018: OncoTargets and Therapy
Motoo Nomura, Atsushi Otsuka, Michio Yoshimura, Yumi Nonomura, Yo Kaku, Shigemi Matsumoto, Manabu Muto
BACKGROUND: The objective of this study was to evaluate the efficacy and safety of concurrent immune checkpoint inhibitor therapy and radiotherapy (immunoradiotherapy) in patients with metastatic melanoma after progression on nivolumab. PATIENTS AND METHODS: A retrospective review was performed on 16 consecutive patients with metastatic melanoma treated with concurrent immunoradiotherapy after progression on nivolumab. Best responses to immunoradiotherapy were assessed either inside or outside of the radiation fields...
March 3, 2018: Cancer Chemotherapy and Pharmacology
Marlana Orloff
The incidence of cutaneous melanoma in the elderly continues to rise. Immunotherapies such as the immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab have shown great promise in the management of this disease. There are growing data, mostly out of clinical trial experience, that shows the efficacy and tolerability of these agents across all ages, including those older than 75 years. Though at first glance immunotherapy for melanoma may appear to be a one-size fits all when it comes to age, a rationale is evolving for why this approach may warrant additional personalization in the older patient...
March 2, 2018: Current Oncology Reports
Haibo Qiu, Zhiwei Zhou
The National Comprehensive Cancer Network (NCCN) issued the clinical practice guidelines for gastric cancer 2017 edition version 5, which has been fully updated for the treatment of gastric cancer, including systematic treatment, surgery and radiotherapy. This article review and summarize the updated NCCN clinical practice guidelines for gastric cancer in 2017 and try to interpret it. (1)Biomarkers: mismatch repair defect (dMMR) or high microsatellite instability (MSI-H), programmed death ligand 1 (PD-L1) and tumor Epstein Barr virus (EBV) status should be considered for patients with gastric cancer...
February 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Michiru Shiba, Hidefumi Inaba, Hiroyuki Ariyasu, Shintaro Kawai, Yuko Inagaki, Shohei Matsuno, Hiroshi Iwakura, Yuki Yamamoto, Masahiro Nishi, Takashi Akamizu
An 80-year-old woman with malignant melanoma received 20 cycles of anti-PD-1 antibody (nivolumab) treatment and showed normal glucose tolerance. Three weeks after switching to anti-CTLA-4 antibody (ipilimumab), her plasma glucose level was elevated to 639 mg/dL, her HbA1c was 7.7%, and her fastening serum CPR was undetectable. Anti-GAD and IA-2 antibodies were negative. She was diagnosed with fulminant type 1 diabetes mellitus (F1DM). Remarkably, her anti-insulin antibody was positively converted, and her KL-6 levels increased after ipilimumab therapy...
February 28, 2018: Internal Medicine
Yanxia Guo, Alice M Walsh, Mary Canavan, Mihir D Wechalekar, Suzanne Cole, Xuefeng Yin, Brittney Scott, Mathew Loza, Carl Orr, Trudy McGarry, Michele Bombardieri, Frances Humby, Susanna M Proudman, Costantino Pitzalis, Malcolm D Smith, Joshua R Friedman, Ian Anderson, Loui Madakamutil, Douglas J Veale, Ursula Fearon, Sunil Nagpal
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development...
2018: PloS One
Linda Chen, Jacqueline Douglass, Lawrence Kleinberg, Xiaobu Ye, Ariel E Marciscano, Patrick M Forde, Julie Brahmer, Evan Lipson, William Sharfman, Hans Hammers, Jarushka Naidoo, Chetan Bettegowda, Michael Lim, Kristin J Redmond
PURPOSE: To characterize the effect of concurrent stereotactic radiosurgery-stereotactic radiation therapy (SRS-SRT) and immune checkpoint inhibitors on patient outcomes and safety in patients with brain metastases (BMs). METHODS AND MATERIALS: We retrospectively identified metastatic non-small cell lung cancer, melanoma, and renal cell carcinoma patients who had BMs treated with SRS-SRT from 2010 to 2016 without prior whole-brain radiation therapy. We included SRS-SRT patients who were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) and anti-programmed cell death protein 1 receptor (nivolumab, pembrolizumab)...
March 15, 2018: International Journal of Radiation Oncology, Biology, Physics
Hiroyuki Ariyasu, Hidefumi Inaba, Takayuki Ota, Hiroyuki Yamaoka, Yasushi Furukawa, Hiroshi Iwakura, Naotaka Doi, Yuki Yamamoto, Takashi Akamizu
BACKGROUND: Immune-checkpoint inhibitors (ICIs) are novel promising agents for the treatment of malignant tumors. However, critical endocrine immune-related adverse events (irAEs) by ICIs often occur. CASE REPORT: A 63-year-old woman with advanced malignant melanoma had received anti-PD-1 antibody (nivolumab, 2 mg/kg every 3 weeks) for 8 cycles (from day 0 to day 147). On day 168, nivolumab was switched to anti-CTLA-4 antibody (ipilimumab, 3mg/kg every 3 weeks)...
March 2018: In Vivo
Gisele Alborghetti Nai, Andressa Bazan, Caroline Andrade Rocha, Juliana Souza Nagy, Isadora Tanaka Campos
Melanomas of the female genital tract may occur in the vulva, the vagina, the ovary or the cervix. Pregnancy has been considered an aggravating factor in the evolution and prognosis of melanoma. A 35-year-old female presented with vaginal bleeding 2 months after a term cesarean delivery. An endovaginal ultrasound revealed a lesion in the uterine cervix. The pathological report revealed a small round-cell neoplasm, and the immunohistochemistry confirmed the diagnosis of malignant melanoma. A positron emission tomography revealed an expansive hypermetabolic lesion centered on the cervix, and hypermetabolic lesions in the liver and right kidney...
February 23, 2018: Revista Brasileira de Ginecologia e Obstetrícia
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