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Nivolumab hodgkin lymphoma

Fabian Finkelmeier, Oliver Waidmann, Joerg Trojan
T-cell checkpoint inhibition as a cancer treatment approach has been the main breakthrough in cancer treatment during the last years. Since the approval of the first commercial CTLA-4 antibody ipilimumab in 2011 for the treatment of melanoma, research and drug development in this field has accelerated massively. In 2014 the US Food and Drug Administration (FDA) approved the first PD-1 targeting agent, namely pembrolizumab, shortly followed by nivolumab. Areas covered: Nivolumab is a fully human immunoglobulin G4 anti-PD-1 monoclonal antibody which is approved for multiple advanced malignancies, including melanoma, non-small cell lung cancer, renal cell cancer, Hodgkin's lymphoma, squamous head and neck cancer and urothelial carcinoma...
October 10, 2018: Expert Review of Anticancer Therapy
Reyad Dada, Yazeed Zabani
Objectives Cancer can escape the immune system through different mechanisms. One such mechanism is the expression of program death ligand-1 which binds to PD-1 receptor on activated T cells, subsequently leading to inhibition of the immune response against cancer cells. Nivolumab is a novel antibody that binds to PD-1 and prevents such immune tolerance. Two recently published controlled clinical trials confirmed the clinical efficacy of single-agent nivolumab in pretreated patients with classical Hodgkin lymphoma...
September 26, 2018: Journal of Oncology Pharmacy Practice
Stephen M Ansell
Classic Hodgkin lymphoma has a unique tumor composition in that there is a paucity of malignant cells present, and most of the tumor consists of normal immune and stromal cells. Despite the presence of an immune infiltrate within the tumor microenvironment, the malignant cells effectively evade the immune system and appear to utilize the presence of immune cells to promote the growth and survival of Hodgkin-Reed-Sternberg cells. Hodgkin-Reed-Sternberg cells evade immune detection because of overexpression of programmed death 1 ligands, PD-L1 and PD-L2, which suppress T-cell activation, and loss of expression of major histocompatibility complex molecules that prevent effective immune recognition...
September 2018: Cancer Journal
Michael A Spinner, Ranjana H Advani, Joseph M Connors, Jacques Azzi, Catherine Diefenbach
Hodgkin lymphoma treatment continues to evolve as new means of assessing response to treatment, new appreciation of important risk factors, and more effective therapeutic agents become available. Treatment algorithms integrating functional imaging now provide the opportunity to modify therapy during its delivery, allowing adjustment of duration and intensity of chemotherapy and rationale identification of patients who may benefit from the addition of therapeutic irradiation. Novel agents, including the antibody drug conjugate brentuximab vedotin and checkpoint inhibitors such as nivolumab and pembrolizumab can improve the effectiveness of treatment while keeping toxicity within acceptable limits...
May 23, 2018: American Society of Clinical Oncology Educational Book
Joanna Zurko, Amitkumar Mehta
Immune-mediated encephalitis related to immune checkpoint inhibitor therapy is a rare but increasingly described condition that can cause significant morbidity. There are several reported cases in the literature but no previously described cases of immune-mediated cerebellitis. We describe a case of acute cerebellitis that developed in a 20-year-old man with primary refractory Hodgkin lymphoma being treated with the immune checkpoint inhibitor nivolumab. After exposure to 3 cycles of nivolumab, the patient had acute onset of headache, ataxia, nausea, and vomiting, with imaging findings of cerebellar edema, early tonsillar herniation, and early hydrocephalus...
March 2018: Mayo Clinic proceedings. Innovations, quality & outcomes
Awais Ijaz, Ali Younas Khan, Saad Ullah Malik, Warda Faridi, Muhammad Asad Fraz, Muhammad Usman, Muhammad Junaid Tariq, Seren Durer, Ceren Durer, Atlantis Russ, Nadia Nunes Cavalcante Parr, Zeeshan Baig, Fnu Sagar, Zeeshan Ali, Ali McBride, Faiz Anwer
Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT...
September 6, 2018: Biology of Blood and Marrow Transplantation
Paul J Bröckelmann, Dennis A Eichenauer, Tina Jakob, Markus Follmann, Andreas Engert, Nicole Skoetz
BACKGROUND: Hodgkin lymphoma is the most common neoplasm in young adults, with an incidence of 2 to 3 cases per 100 000 persons per year. Risk-adapted chemotherapy and radiotherapy usually lead to cure. Finding ways to lessen the treatment- associated morbidity and mortality is a major goal of current research. METHODS: For the creation of an updated guideline (DKH grant number 111778), a systematic literature search was carried out in medical databases (MEDLINE, CENTRAL) and guideline databases (GIN) (search dates: January 2012 to June 2017)...
August 6, 2018: Deutsches Ärzteblatt International
Lingdi Zhao, Yonghao Yang, Wei Li, Tiepeng Li, Quanli Gao
Hodgkin's lymphoma is a common malignant disease, especially among children in America. Although chemotherapy and radiotherapy are mainstay treatments for Hodgkin's lymphoma, a small portion of patient experiences relapsed or refractory diseases. Nivolumab provides an option for patients who experience relapsed or refractory disease, but adverse effects may occur. Here, we report a patient with relapsed/refractory Hodgkin's lymphoma who experienced cytokine-release syndrome after his first dose of nivolumab...
August 2018: Immunotherapy
Santosha Vardhana, Kara Cicero, Moises J Velez, Craig H Moskowitz
The programmed death-1 (PD-1) receptor checkpoint inhibitors nivolumab and pembrolizumab represent an important therapeutic advance in the treatment of relapsed or refractory classical Hodgkin lymphoma (cHL). Clinical trials have shown substantial therapeutic activity and an acceptable safety profile in heavily pretreated patients, resulting in U.S. Food and Drug Administration approval of nivolumab for the treatment of cHL that has relapsed or progressed after either autologous hematopoietic cell transplantation (auto-HCT) and brentuximab vedotin treatment or three or more lines of systemic therapy (including auto-HCT), and of pembrolizumab for adult or pediatric patients with refractory cHL or cHL that has relapsed after three or more prior therapies...
August 6, 2018: Oncologist
Angelo Castello, Fabio Grizzi, Dorina Qehajaj, Daoud Rahal, Fabio Lutman, Egesta Lopci
Our aim was to evaluate Hodgkin Lymphoma (HL) response to checkpoint inhibitors with 18 F-FDG PET/CT. Forty three refractory or relapsed HL patients were investigated before immunotherapy, 8 weeks and 17 weeks after administration of either nivolumab or pembrolizumab. The median follow-up was 19 months. Best clinical response was complete response (CR) in 26 patients, partial response (PR) in 5 patients, stable disease (SD) in 8 patients, and progression disease (PD) in 4 patients. At the early assessment, Deauville Score (DS) resulted significantly different in responder group compared to nonresponders...
July 22, 2018: Leukemia & Lymphoma
Elaine Chang, Anita L Sabichi, Jennifer R Kramer, Christine Hartman, Kathryn E Royse, Donna L White, Niraj R Patel, Peter Richardson, Sarvari V Yellapragada, Jose M Garcia, Elizabeth Y Chiao
Nivolumab is a standard treatment option in several advanced malignancies, but safety and efficacy are still unknown in patients with human immunodeficiency virus (HIV) infection. We describe a case series of people living with HIV (PLWH) receiving nivolumab in the Veterans Health Administration (VA) and report responses and toxicities. We identified all PLWH who received nivolumab at any VA facility since 2000 in the Corporate Data Warehouse (CDW), which provides nationwide research access to VA electronic medical records...
October 2018: Journal of Immunotherapy
Kristina Buder-Bakhaya, Jessica C Hassel
Background: Immune checkpoint inhibition (ICI) with anti-CTLA-4 and/or anti-PD-1 antibodies is standard treatment for metastatic melanoma. Anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for treatment of several other advanced malignancies, including non-small-cell lung cancer (NSCLC); renal cell, and urothelial carcinoma; head and neck cancer; gastric, hepatocellular, and Merkel-cell carcinoma; and classical Hodgkin lymphoma...
2018: Frontiers in Immunology
Marius Goldkuhle, Maria Dimaki, Gerald Gartlehner, Ina Monsef, Philipp Dahm, Jan-Peter Glossmann, Andreas Engert, Bastian von Tresckow, Nicole Skoetz
BACKGROUND: Hodgkin's lymphoma (HL) is a cancer of the lymphatic system, and involves the lymph nodes, spleen and other organs such as the liver, lung, bone or bone marrow, depending on the tumour stage. With cure rates of up to 90%, HL is one of the most curable cancers worldwide. Approximately 10% of people with HL will be refractory to initial treatment or will relapse; this is more common in people with advanced stage or bulky disease. Standard of care for these people is high-dose chemotherapy and autologous stem cell transplantation (ASCT), but only 55% of participants treated with high-dose chemotherapy and ASCT are free from treatment failure at three years, with an overall survival (OS) of about 80% at three years...
July 12, 2018: Cochrane Database of Systematic Reviews
Gerald Illerhaus, Elisabeth Schorb, Benjamin Kasenda
Primary central nervous system lymphoma (PCNSL) is a rare aggressive extranodal non- Hodgkin lymphoma. Although high remission rates can be achieved with high-dose methotrexate-based immunochemotherapy, risk of relapse and associated death is still substantial in at least a third of patients. Novel agents for treating lymphoid malignancies have substantially enriched treatment options for PCNSL. We herein systematically review the existing clinical evidence of novel agents in treatment of PCNSL, summarize ongoing studies, and discuss perspectives...
August 16, 2018: Blood
Qian Qin, Xinyu Nan, Tara Miller, Ronald Fisher, Bin Teh, Shruti Pandita, Andrew M Farach, Sai Ravi Pingali, Raj K Pandita, E Brian Butler, Tej K Pandita, Swaminathan P Iyer
Until recently, patients with relapsed Hodgkin's lymphoma after brentuximab vedotin (Bv) treatments had poor treatment outcomes. Checkpoint inhibitors such as nivolumab and pembrolizumab that bind to and inhibit programmed cell death protein-1 (PD-1), have demonstrated an overall response rate of 70% in Hodgkin's lymphoma patients; however, complete response is still low at 20% with median progression-free survival of 14 months. There are ongoing clinical studies to seek out synergistic combinations, with the goal of improving the complete response rates for the cure of Hodgkin's lymphoma...
September 2018: Radiation Research
Gunjan L Shah, Craig H Moskowitz
Checkpoint inhibition improves surveillance by the immune system and therefore outcomes in some lymphoma subtypes. In this review, we examine the available evidence regarding checkpoint inhibition in lymphoma by line of therapy. Although most published studies are in the setting of relapsed/refractory disease, several ongoing trials are looking at therapy in the upfront and second-line settings. Nivolumab and pembrolizumab have been approved for patients with relapsed or refractory Hodgkin lymphoma, whereas other programmed death 1 and programmed death ligand 1 monoclonal antibodies remain under investigation as single agents or in combination...
January 2018: Clinical Advances in Hematology & Oncology: H&O
Yucai Wang, Grzegorz S Nowakowski, Michael L Wang, Stephen M Ansell
CD30 and programmed cell death protein 1 (PD-1) are two ideal therapeutic targets in classical Hodgkin lymphoma (cHL). The CD30 antibody-drug conjugate (ADC) brentuximab vedotin and the PD-1 antibodies nivolumab and pembrolizumab are highly efficacious in treating relapsed and/or refractory cHL. Ongoing studies are evaluating their efficacy in earlier lines of therapy and have demonstrated encouraging results. These agents are expected to further change the landscape of cHL management. Increased cure rates and reduced long-term toxicity from traditional chemotherapy and radiotherapy are likely with the emergence of these novel targeted therapies...
April 23, 2018: Journal of Hematology & Oncology
Polina Shindiapina, Lapo Alinari
Immune evasion is a critical mechanism of malignant cell survival, and relies in part on molecular signaling through the programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) axis that contributes to T cell exhaustion. Immune modulatory therapy with monoclonal antibodies against PD-1 designed to enhance antitumor immune response have shown promise in the treatment of advanced solid tumors and hematologic malignancies. Classical Hodgkin's lymphoma (cHL), a unique B cell malignancy characterized by an extensive but ineffective immune cell infiltrate surrounding a small number of tumor cells, has shown significant response to anti-PD-1 directed therapy...
April 2018: Therapeutic Advances in Hematology
Michael Fuchs
Hodgkin Lymphoma is one of the best curable tumor in adults. PET adapted therapy with BEACOPPescalated is standard for 1st line treatment of advanced stage disease and the majority of patient can be sufficiently treated with 4 cycles of BEACOPPescalated only. Maintenance therapy after autologous stem cell transplantation with Brentuximab Vedotin was recently introduced. PD-1 inhibitors such as Nivolumab and Pembrolizumab were approved for the treatment of relapsed Hodgkin Lymphoma after Brentuximab Vedotin...
April 2018: Deutsche Medizinische Wochenschrift
Philippe Armand, Andreas Engert, Anas Younes, Michelle Fanale, Armando Santoro, Pier Luigi Zinzani, John M Timmerman, Graham P Collins, Radhakrishnan Ramchandren, Jonathon B Cohen, Jan Paul De Boer, John Kuruvilla, Kerry J Savage, Marek Trneny, Margaret A Shipp, Kazunobu Kato, Anne Sumbul, Benedetto Farsaci, Stephen M Ansell
Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)-naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C)...
May 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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