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Nivolumab hodgkin lymphoma

Marcin Sokołowski, Anna Sokołowska, Grzegorz Mazur, Aleksandra Butrym
The checkpoint inhibitors have been continuously present in haematology for 20 years. From the first description, several of them were enrolled to the list of the oncological drugs. The research on nivolumab, avelumab, durvolumab is still in progress. In the treatment of some diseases, for instance, Hodgkin lymphoma, the programmed death cell pathway has already an important role. During the last years, the guidelines were enriched by using these drugs, both in solid and haematological malignancies. In this review, we present a history of discovery, research and clinical use of this new class of drugs potentially providing a significant change in curability rates of some haematological malignancies...
March 2019: Critical Reviews in Oncology/hematology
Inmaculada Peiró, Ramón Palmero, Pedro Iglesias, Juan José Díez, Andreu Simó-Servat, Juan Antonio Marín, Laura Jiménez, Eva Domingo-Domenech, Nuria Mancho-Fora, Ernest Nadal, Carlos Villabona
PURPOSE: Nivolumab is a monoclonal antibody that blocks the activation of programmed death-1 receptor, promoting T-cell activation against cancer cells. Thyroid dysfunction (TD) is a common immune-related adverse event (irAE) induced by nivolumab. We report the prevalence, patterns and outcomes of nivolumab-induced TD among cancer patients in our center. METHODS: All patients treated with nivolumab during 2016 were included. We assessed thyroid function tests, thyroid autoimmunity, thyroid imaging, and clinical outcome during nivolumab therapy as well as overall survival (OS)...
February 25, 2019: Endocrine
K Steinerová, P Jindra, D Lysák, M Karas
BACKGROUND: Allogeneic hematopoietic stem cell transplantation is one of the therapeutic options for patients with relapsed or refractory classic Hodgkins lymphoma (cHL). In the case of dis-ease relapse after transplant, other treatment options are still limited (for example donor lymphocyte infusion, and chemother-apy with brentuximab, bendamustine, or other agents) with uncertain outcomes in terms of patient tolerance and long-term dis-ease remission. One way to achieve remission is administration of the PD-1 inhibitor nivolumab, a PD-1 checkpoint inhibitor...
2019: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
A Amraee, M R Evazi, M Shakeri, N Roozbeh, M Ghazanfarpour, M Ghorbani, J Ansari, L Darvish
AIMS: The primary standard treatment for classic Hodgkin's lymphoma (cHL) is chemotherapy and radiation therapy. However, some patients get relapsed, or their diseases become resistant. PD1 blocking antibodies have been used to increase the response of treatment in solid tumors, and led to potentially stable responses that are acceptable. Our purpose in this study is to investigate the effect of nivolumab as a PD1 blocking antibody on the survival rate of patients with Hodgkin's cancer...
February 9, 2019: Clinical & Translational Oncology
Kirill V Lepik, Natalia B Mikhailova, Ivan S Moiseev, Elena V Kondakova, Luibov A Tsvetkova, Yuri R Zalyalov, Evgeniya S Borzenkova, Elena V Babenko, Vadim V Baykov, Inna V Markova, Boris V Afanasyev
No abstract text is available yet for this article.
February 4, 2019: Leukemia & Lymphoma
J Rogado, J M Sánchez-Torres, N Romero-Laorden, A I Ballesteros, V Pacheco-Barcia, A Ramos-Leví, R Arranz, A Lorenzo, P Gullón, O Donnay, M Adrados, P Costas, J Aspa, A Alfranca, R Mondéjar, R Colomer
BACKGROUND: Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy. PATIENTS AND METHODS: We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer...
January 22, 2019: European Journal of Cancer
Anas Younes, Joshua Brody, Cecilia Carpio, Armando Lopez-Guillermo, Dina Ben-Yehuda, Burhan Ferhanoglu, Arnon Nagler, Muhit Ozcan, Irit Avivi, Francesc Bosch, Maria Dolores Caballero Barrigón, Andrzej Hellmann, Bryone Kuss, David D F Ma, Fatih Demirkan, Münci Yağci, Netanel A Horowitz, Paula Marlton, Raul Cordoba, Tomasz Wrobel, Daniela Buglio, Michael Streit, Brendan P Hodkinson, Michael Schaffer, John Alvarez, Rob Ceulemans, Sriram Balasubramanian, Jan de Jong, Shean-Sheng Wang, Nele Fourneau, Wojciech Jurczak
BACKGROUND: Preclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed or refractory B-cell malignant diseases. METHODS: We did a two-part, open-label, phase 1/2a study at 21 hospitals in Australia, Israel, Poland, Spain, Turkey, and the USA. The primary objective of part A (dose escalation) was to assess the safety of daily oral ibrutinib (420 mg or 560 mg) in combination with intravenous nivolumab (3 mg/kg every 2 weeks) to ascertain a recommended phase 2 dose in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma (del17p or del11q), follicular lymphoma, or diffuse large B-cell lymphoma...
February 2019: Lancet Haematology
Marie Dilly-Feldis, Nathalie Aladjidi, John K Refait, Marie Parrens, Stéphane Ducassou, Anne Rullier
BACKGROUND: Although a prognosis of recurrent or refractory childhood Hodgkin lymphoma (HL) is associated with poor outcomes despite intensive therapy, the immune checkpoint inhibitors PD-1/PD-L1 appear to be therapeutic alternatives for advanced adult cases. However, these pharmacotherapies are yet to be studied in a pediatric population. PROCEDURE: The present study measured the expression of PD-1/PD-L1 in diagnostic samples of children with classical HL, according to the disease course...
January 13, 2019: Pediatric Blood & Cancer
Takahiro Kobayashi, Yong-Mei Guo, Takaya Yamashita, Miho Nara, Tomoko Yoshioka, Yoshihiro Kameoka, Takahiro Fukuda, Naoto Takahashi
Although programmed cell death (PD)-1 blockade induces immune-related adverse events (irAEs), little is known about the safety of PD-1 blockade after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we describe immune system changes during nivolumab-related myositis in a patient with Hodgkin's lymphoma after allogeneic HSCT; to our knowledge, this is the first such report in the literature. At the onset of myositis, the patient lost lower limb mobility against gravity, and had an activated immune profile with increased cytotoxic CD107a and granzyme B expression, as well as pro-inflammatory cytokines, interferon-γ, tumor necrosis factor-α, interleukin-2 in T and NK cells compared to healthy donor...
January 3, 2019: International Journal of Hematology
Laurent Gilardin, Sandy Amorim, Sophie Bernard, Odonchimeg Ravdan, Catherine Thieblemont, Pauline Brice
Classical Hodgkin lymphoma (HL) is a rare hematological cancer, affecting preferentially young adults. Using a risk-adapted approach, HL has become highly curable (>80%) with front-line chemotherapy in addition with radiotherapy, despite long term significant toxicity. Some patients are primary refractory or relapse after first-line chemotherapy, requiring high dose chemotherapy with serious side effects. Studies of the microenvironment from HL tissue reveal ineffective inflammatory and immune cell infiltrate surrounding Reed-Sternberg cells, involving the Programmed cell Death 1 (PD-1)/PD-ligand-1 checkpoint pathways...
December 2018: Bulletin du Cancer
Steven M Bair, Lauren E Strelec, Tatyana A Feldman, Gulrayz Ahmed, Philippe Armand, Nirav N Shah, Arun N Singavi, Nishitha Reddy, Nadia Khan, Charalambos Andreadis, Khoan Vu, Scott F Huntington, Smith Giri, Chaitra Ujjani, Christina Howlett, Malik Faheem, Matthew R Youngman, Sunita D Nasta, Daniel J Landsburg, Stephen J Schuster, Jakub Svoboda
BACKGROUND: Although classical Hodgkin lymphoma (cHL) is highly curable, 20%-30% of patients will not be cured with conventional treatments. The programmed death-1 (PD-1) inhibitors (PD-1i) nivolumab and pembrolizumab have been Food and Drug Administration-approved for relapsed/refractory (R/R) cHL. There is limited data on the real-world experience with PD-1i in cHL and it is unknown whether fewer selected patients treated with PD-1i derive benefits similar to those observed in published trials...
December 19, 2018: Oncologist
Gottfried von Keudell, Anas Younes
Hodgkin Lymphoma (HL) is a B-cell lymphoproliferative disorder with an excellent prognosis for the majority of patients who are treated with multi-agent chemotherapy, with or without radiation. A subset of patient, however, does not respond to therapy or relapses after accomplishing an initial response. Their outcome is poor and new treatment strategies are urgently needed for this patient population. Recent advances in the understanding of the tumour biology of HL and its microenvironment have ushered a new era of targeted- and immuno-therapies with remarkable activity...
December 11, 2018: British Journal of Haematology
Alex F Herrera
Genetic alterations of the PD-L1 / PD-L2 locus on chromosome 9p24.1 are a defining biological feature of classical Hodgkin lymphoma (HL). The resulting programmed death-ligand 1 (PD-L1) expression on Hodgkin Reed-Sternberg cells as well as the PD-L1 expressed in the HL microenvironment result in an ineffective host antitumor immune response and make HL a ripe target for programmed cell death-1 (PD-1) blockade. Anti-PD-1 antibody monotherapy has been effective and well tolerated in patients with relapsed or refractory (rel/ref) HL, with the majority of patients experiencing an objective response (approximately two-thirds of patients) and a median duration of response of 16...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Panayotis Kaloyannidis, Eshrak Al Shaibani, Miral Mashhour, Mohammed Gamil, Ioannis Apostolidis, Hani Al Hashmi, Khalid Ahmed Al Anazi
The programmed cell death protein-1 (PD-1) inhibitor nivolumab has been recently approved as an effective and safe treatment for patients with refractory/relapsed Hodgkin's lymphomas. Dermatological adverse events, mainly skin rash, have been reported in 1-5% of patients. We describe a case of de novo psoriasis vulgaris (PsV), diagnosed after nivolumab treatment for refractory Hodgkin's lymphoma. After administration of 6 cycles, skin lesions appeared in the right tibia, forearms, and dorsum of hands, and biopsy confirmed the diagnosis of PsV...
2018: Case Reports in Hematology
Boris Böll, Helen Görgen
The outcome of patients with Hodgkin lymphoma (HL) has dramatically improved over the past decades and continues to improve with the development of novel targeted therapies, such as the immunoconjugate brentuximab vedotin and the checkpoint inhibitors nivolumab and pembrolizumab. Moreover, with the use of response-adapted strategies using positron-emission-tomography (PET), the overall intensity of treatment for most patients can be reduced, resulting in less acute and late toxicity. However, these advances are mainly restricted to younger patients, as advances in patients above the age of 60 years ('older' patients) have been much less pronounced...
November 8, 2018: British Journal of Haematology
Xiaoli Wang, Elizabeth A Ludwig, Julie Passarell, Akintunde Bello, Amit Roy, Matthew W Hruska
Nivolumab, a fully human immunoglobulin G4 monoclonal anti-programmed death-1 antibody, has demonstrated clinical benefits in multiple tumors, including classical Hodgkin lymphoma. The aim of this study was to characterize the pharmacokinetics (PK) of nivolumab in patients with classical Hodgkin lymphoma using a population approach and to assess the exposure-response (E-R) relationship for safety, thereby supporting the dose recommendation in patients with classical Hodgkin lymphoma. Nivolumab PK and the effect of covariates were consistent with that observed in solid tumors, except that baseline clearance of nivolumab was lower in patients with classical Hodgkin lymphoma by 28%...
October 19, 2018: Journal of Clinical Pharmacology
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...
December 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
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