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Refractory follicular lymphoma

Loretta J Nastoupil, Christopher R Flowers, John P Leonard
Follicular lymphoma (FL) is an incurable but treatable disease with vast treatment options. Despite the abundance of efficacious treatment modalities, there is no universally agreed upon standard approach to treatment, particularly in the relapsed/refractory setting. There is an increasing need for more robust and clinically available tools to risk-stratify patients and identify those likely to experience early relapse, which is currently recognized as the unmet need in FL. Additionally, the use of gene-expression profiling and next-generation sequencing techniques in recent years has led to a wealth of knowledge regarding the molecular drivers of lymphomagenesis...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
(no author information available yet)
The anti-CD47 drug Hu5F9-G4, also known as 5F9, in combination with the anti-CD20 therapy rituximab, may be a promising treatment for some forms of non-Hodgkin lymphoma because it allows macrophages to recognize and attack cancer cells. In a phase Ib trial testing the combination, patients with relapsed/refractory diffuse large B-cell lymphoma or follicular lymphoma had an objective response rate of 50% and few side effects.
November 21, 2018: Cancer Discovery
Hannah A Blair
Duvelisib (Copiktra™) is a small-molecule inhibitor of phosphatidylinositol-3 kinase that has been developed as an oral treatment for various cancer indications. In September 2018, duvelisib received its first global approval in the USA for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) after at least two prior therapies. Duvelisib was also granted accelerated approval in the USA for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies...
November 14, 2018: Drugs
Katsuyoshi Takata, Ken Saito, Satoshi Maruyama, Tomoko Miyata-Takata, Hidekazu Iioka, Shujiro Okuda, Yiwei Ling, Kennosuke Karube, Yukari Miki, Yoshinobu Maeda, Tadashi Yoshino, Christian Steidl, Eisaku Kondo
Despite receiving rituximab-combined chemotherapy, follicular lymphoma (FL) patients often suffer tumor recurrence, and understand the cause of relapse in FL would thus significantly ameliorate the tumor therapeutics. Here we demonstrate that the TRA-1-60-expressing cells are a unique population in FLs, converge to the conventional stem cell marker Oct3/4 and ALDH1-positive population, and resist current B-lymphoma agents. TRA-1-60 expression was observed only in scattered lymphoma cells in FL tissues as well as resting B-lymphocytes inside germinal centers...
November 11, 2018: Cancer Science
(no author information available yet)
The FDA approved duvelisib, a PI3Kδ/PI3Kγ inhibitor, for patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma who have received at least two prior therapies. The agency also granted the drug an accelerated approval for patients with relapsed/refractory follicular lymphoma following at least two other therapies.
October 23, 2018: Cancer Discovery
Greg P Coffey, Greg P Coffey, Andreas Betz, Jiajia Feng, Anjali Pandey, Matt Birrell, Janet M Leeds, Kenneth Der, Sabah Kadri, Pin Lu, Jeremy P Segal, Y Lynn Wang, Glenn Michelson, John T Curnutte, Pamela B Conley
PURPOSE: Preclinical studies suggest SYK and JAK contribute to tumor intrinsic and microenvironment-derived survival signals. The pharmacodynamics of cerdulatinib, a dual SYK/JAK inhibitor, and associations with tumor response were investigated. EXPERIMENTAL DESIGN: In a phase I dose-escalation study in adults with relapsed/refractory B-cell malignancies, cerdulatinib was administered orally to sequential dose-escalation cohorts using once-daily or twice-daily schedules...
October 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Toby A Eyre, Graham P Collins, Avinash Gupta, Nicholas Coupe, Semira Sheikh, John Whittaker, Lai Mun Wang, Leticia Campo, Elizabeth Soilleux, Finn Tysoe, Richard Cousins, Nick La Thangue, Lisa K Folkes, Michael R L Stratford, David Kerr, Mark R Middleton
BACKGROUND: In the current study, the authors sought to determine the maximum tolerated dose (MTD) of the novel class 1 selective histone deacetylase inhibitor CXD101 in a dose escalation study in patients with advanced solid tumors or recurrent/refractory lymphoma. METHODS: The authors escalated the dose of CXD101 from 1 mg twice daily orally for 5 days in a 21-day cycle (3+3 design). RESULTS: A total of 39 patients were enrolled, 36 of whom received CXD101...
October 17, 2018: Cancer
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...
November 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
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