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Refractory follicular lymphoma

Kai Hübel
The overall prognosis for patients with relapsed or refractory aggressive non-Hodgkin's lymphomas is poor. Only a minority of patients are able to receive autologous stem cell transplantation. Patients not transplant-eligible or patients relapsing after transplantation have an urgent need for effective treatment options. Pixantrone is the only compound approved in Europe for this situation. Areas covered: This review describes the clinical development of pixantrone, starting with phase I trials up to phase III trials in order to define the role of pixantrone in treatment algorithms...
October 1, 2018: Expert Opinion on Pharmacotherapy
David J Andorsky, Kathryn S Kolibaba, Sarit Assouline, Andres Forero-Torres, Vicky Jones, Leonard M Klein, Dipti Patel-Donnelly, Mitchell Smith, Wei Ye, Wen Shi, Christopher A Yasenchak, Jeff P Sharman
Spleen tyrosine kinase (Syk) mediates B-cell receptor signalling in normal and malignant B cells. Entospletinib is an oral, selective Syk inhibitor. Entospletinib monotherapy was evaluated in a multicentre, phase 2 study of patients with relapsed or refractory indolent non-Hodgkin lymphoma or mantle cell lymphoma (MCL). Subjects received 800 mg entospletinib twice daily. Forty-one follicular lymphoma (FL), 17 lymphoplasmacytoid lymphoma/Waldenström macroglobulinaemia (LPL/WM), 17 marginal zone lymphoma (MZL) and 39 MCL patients were evaluated...
September 5, 2018: British Journal of Haematology
Michał Kwiatek, Łukasz Pruchniewski, Joanna Kwiatek, Maciej Kaźmierczak, Krzysztof Lewandowski
Follicular lymphoma (FL) is the most common of indolent non-Hodgkin's lymphomas. Its first-line treatment, based on immuno-chemotherapy with the anti-CD20 monoclonal antibody rituximab, is characterized by a high overall response rate to therapy. However, the disease is not curable in most cases and frequent relapses and transformations to other higher-grade lymphomas are observed. The effectiveness of the treatment of relapsed or refractory FL is not satisfactory, therefore the novel drugs are under investigation...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Hervé Tilly, Franck Morschhauser, Olivier Casasnovas, Thierry Jo Molina, Pierre Feugier, Steven Le Gouill, Corinne Haioun, Olivier Tournilhac, Reda Bouabdallah, Jean Gabarre, Thierry Lamy, José Cabeçadas, Stéphanie Becker, Fabrice Jardin, Nicolas Mounier, Gilles Salles
BACKGROUND: Immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is a standard front-line treatment for follicular lymphoma. The combination of lenalidomide and rituximab has shown high efficacy in relapsed or refractory and untreated follicular lymphoma. We aimed to evaluate the safety and activity of the combination of lenalidomide and R-CHOP (R2-CHOP) in previously untreated patients with high burden follicular lymphoma. METHODS: This single-arm, open-label, multicentre, phase 2 trial was done in 16 hospitals in France, all of which were Lymphoma Study Association (LYSA) sites...
September 2018: Lancet Haematology
Felix A Mensah, Jean-Pierre Blaize, Locke J Bryan
The importance of the phosphatidylinositol-3-kinase (PI3K) pathway in cell survival and proliferation has made it an attractive target in cancer therapy. The development of small molecule inhibitors for the PI3K pathway continues to provide treatment alternatives across a range of malignancy types. Several agents, including idelalisib, copanlisib and duvelisib, not only inhibit the PI3K pathway, but also have effects on associated mechanisms including the ATK and mTOR pathways. The advent of PI3K-specific small molecular inhibitors has led to increased efficacy with avoidance of an excessive toxicity profile...
2018: OncoTargets and Therapy
Tycel Phillips, Paul M Barr, Steven I Park, Kathryn Kolibaba, Paolo F Caimi, Saurabh Chhabra, Edwin C Kingsley, Thomas Boyd, Robert Chen, Anne-Sophie Carret, Elaina M Gartner, Hong Li, Cindy Yu, David C Smith
Purpose This first-in-human study evaluated SGN-CD70A, an antibody-drug conjugate (ADC) directed against the integral plasma membrane protein CD70 and linked to a pyrrolobenzodiazepine (PBD) dimer, in patients with relapsed or refractory (R/R) CD70-positive non-Hodgkin lymphoma (NHL) including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Grade 3b follicular lymphoma (FL3b). Methods SGN-CD70A was administered intravenously on Day 1 of 3-week cycles beginning at 8 mcg/kg with planned dose escalation to 200 mcg/kg...
August 22, 2018: Investigational New Drugs
Aaron Galaznik, Rachel Huelin, Michael Stokes, Yelan Guo, Meredith Hoog, Tarun Bhagnani, Jill Bell, Yaping Shou
To identify real-world evidence on outcomes from therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), we systematically reviewed literature in Medline/Embase for DLBCL/FL-related articles on real-world results published during January 2012-May 2016. Among 33 included articles, therapies included stem cell transplant (SCT) and chemotherapy, including experimental regimens. The highest overall survival rates were observed for SCT, long considered an optimal strategy following initial relapse...
July 2018: Future Science OA
S de Vos, L J Swinnen, D Wang, E Reid, N Fowler, J Cordero, M Dunbar, S H Enschede, C Nolan, A M Petrich, J A Ross, A H Salem, M Verdugo, S Agarwal, L Zhou, M Kozloff, L J Nastoupil, C R Flowers
Background: Venetoclax is a selective, potent inhibitor of the anti-apoptotic B-cell leukemia/lymphoma-2 protein approved for treatment of chronic lymphocytic leukemia. We conducted a dose-finding study of venetoclax in combination with bendamustine-rituximab (BR) in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL). Patients and methods: BR was given for six cycles at standard doses. Intermittent and continuous oral venetoclax administration was explored at 50-1200 mg daily doses...
September 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Theo Pirich, Elisabeth Zwickl-Traxler, Martin Pecherstorfer, Josef Singer
Background & Aim: In randomised clinical trials, the type II anti-CD20 antibody obinutuzumab has been shown to be more effective than rituximab for therapy of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). However, this enhanced efficacy was linked with elevated rates of high-grade adverse events. The aim of this study was to assess the tolerability and toxicity profile of obinutuzumab treatment in routine patients with CLL and FL, of whom the majority had experienced toxicity or resistance to rituximab...
July 6, 2018: Oncotarget
(no author information available yet)
A recently reported clinical trial indicates that the EZH2 inhibitor tazemetostat is effective against relapsed or refractory follicular lymphoma. Three of 28 patients with EZH2 mutations had complete responses, and 17 had partial responses.
August 2018: Cancer Discovery
Frank Stenner, Christoph Renner
Follicular lymphoma (FL) is the most frequent indolent lymphoma in the Western world and is characterized in almost all cases by the t(14;18) translocation that results in overexpression of BCL2, an anti-apoptotic protein. The entity includes a spectrum of subentities that differ from an indolent to a very aggressive growth pattern. As a consequence, treatment can include watch & wait up to intensive chemotherapy including allogeneic stem cell transplantation. The immune cell microenvironment has been recognized as a major driver of outcome of FL patients and gene expression profiling has identified a clinically relevant gene expression signature that classifies an immune response to the lymphoma cells...
2018: Frontiers in Oncology
Preetesh Jain, Sergej Konoplev, Ohad Benjamini, Jorge Romagura, Jan A Burger
No abstract text is available yet for this article.
June 2018: Blood Research
Lorenzo Falchi, Alessandra Ferrajoli, Ira Jacobs, Pilar Nava-Parada
Combination regimens with anti-CD20 agents might improve the outcomes of patients with relapsed or refractory B-cell malignancies; however, the available comparative clinical evidence is limited. The present review assessed the reported evidence on the efficacy of anti-CD20 monoclonal antibodies combined with chemotherapy for patients with relapsed or refractory chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), or diffuse large B-cell lymphoma (DLBCL), using a rapid evidence assessment approach...
August 2018: Clinical Lymphoma, Myeloma & Leukemia
Fredrik Salvesen Haukaas, Audun Ohna, Tania Krivasi
AIMS: To evaluate the cost-effectiveness of obinutuzumab in combination with bendamustine followed by obinituzumab maintenance (Obin-Benda) compared to bendamustine alone (Benda) in patients with refractory follicular lymphoma (FL) in a Norwegian setting. METHODS: A three-state area-under-the-curve (AUC) model was developed. The states included were progression-free-survival (PFS), progressed disease (PD), and death. Each state had costs and utilities assigned to it...
June 19, 2018: Applied Health Economics and Health Policy
Julio C Chavez, Frederick L Locke
B-cell non-Hodgkin's lymphoma (NHLs)is a very heterogonous malignancy with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) as the most common subtypes. Standard treatment with anti-CD20 based chemoimmunotherapy is usually very effective for disease control. However a significant proportion of patients with high-risk features (double hit lymphoma, transformed lymphomas or early relapses) will become refractory to standard therapies and will have limited alternatives for cure. Adoptive therapy with chimeric antigen receptor (CAR) T-cells is a new paradigm for effective treatment of poor prognosis lymphomas...
June 2018: Best Practice & Research. Clinical Haematology
Gregory F Guzauskas, Anthony Masaquel, Carolina Reyes, Coen Bernaards, Tania Krivasi, David L Veenstra
AIMS: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G + B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy...
October 2018: Journal of Medical Economics
Andrew M Intlekofer, Erel Joffe, Connie L Batlevi, Patrick Hilden, Jie He, Venkatraman E Seshan, Andrew D Zelenetz, M Lia Palomba, Craig H Moskowitz, Carol Portlock, David J Straus, Ariela Noy, Steven M Horwitz, John F Gerecitano, Alison Moskowitz, Paul Hamlin, Matthew J Matasar, Anita Kumar, Marcel R van den Brink, Kristina M Knapp, Janine D Pichardo, Michelle K Nahas, Sally E Trabucco, Tariq Mughal, Amanda R Copeland, Elli Papaemmanuil, Mathai Moarii, Ross L Levine, Ahmet Dogan, Vincent A Miller, Anas Younes
We sought to define the genomic landscape of diffuse large B-cell lymphoma (DLBCL) by using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. We studied 198 samples (114 de novo, 58 previously treated, and 26 large-cell transformation from follicular lymphoma)...
June 12, 2018: Blood Cancer Journal
Peter Martin
No abstract text is available yet for this article.
April 2018: Clinical Advances in Hematology & Oncology: H&O
Ajay K Gopal, Stephen J Schuster, Nathan H Fowler, Judith Trotman, Georg Hess, Jing-Zhou Hou, Abdulraheem Yacoub, Michael Lill, Peter Martin, Umberto Vitolo, Andrew Spencer, John Radford, Wojciech Jurczak, James Morton, Dolores Caballero, Sanjay Deshpande, Gary J Gartenberg, Shean-Sheng Wang, Rajendra N Damle, Michael Schaffer, Sriram Balasubramanian, Jessica Vermeulen, Bruce D Cheson, Gilles Salles
Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee-assessed overall response rate (ORR; complete response plus partial response)...
August 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Yan Qin, Yuqin Song, Zhixiang Shen, Xin Du, Wei Ji, Wanling Hsu, Jun Zhu, Yuankai Shi
BACKGROUND: Patients with relapsed/refractory B-cell lymphomas have limited treatment options. GERSHWIN is an open-label, single-arm, phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically documented CD20+ relapsed/refractory chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL). The primary outcome measure of pharmacokinetics has been previously reported. We now present data on the secondary endpoint measures (e...
May 30, 2018: Cancer communications
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