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Refractory follicular lymphoma

Andres Forero-Torres, Radhakrishnan Ramchandren, Abdulraheem Yacoub, Michael S Wertheim, William J Edenfield, Paolo Caimi, Martin Gutierrez, Luke Akard, Carolina Escobar, Justin Call, Daniel Persky, Swaminathan Iyer, Douglas J DeMarini, Li Zhou, Xuejun Chen, Fitzroy Dawkins, Tycel J Phillips
This phase 1/2 study assessed parsaclisib (INCB050465), a next-generation, potent, and highly selective phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor, in patients with relapsed or refractory B-cell malignancies, alone or in combination with a Janus kinase 1 inhibitor (itacitinib) or chemotherapy (rituximab, ifosfamide, carboplatin, and etoposide). Seventy-two patients received parsaclisib monotherapy (5-45 mg once daily). Expansion doses were 20 and 30 mg once daily; intermittent dosing at 20 mg (once daily for 9 weeks, then once weekly) was explored...
February 25, 2019: Blood
Gilles Salles, Ajay K Gopal, Monique C Minnema, Karen Wakamiya, Huaibao Feng, Jordan M Schecter, Michael Wang
BACKGROUND: Daratumumab is a CD38 monoclonal antibody approved for treating relapsed/refractory and newly diagnosed multiple myeloma. Preclinical daratumumab studies demonstrated cytotoxic activity and reduced tumor growth in B-cell non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle-cell lymphoma (MCL). PATIENTS AND METHODS: This was a phase 2, open-label, multicenter, 2-stage trial. Patients with relapsed/refractory DLBCL, FL, or MCL with ≥ 50% CD38 expression were eligible for stage 1...
January 2, 2019: Clinical Lymphoma, Myeloma & Leukemia
(no author information available yet)
No abstract text is available yet for this article.
February 2019: Hematological Oncology
Helen Ma, Owen A O'Connor, Enrica Marchi
The peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of non-Hodgkin lymphomas originating from mature T- and NK-cells. They are aggressive diseases often resistant to chemotherapy. Areas Covered: The methodology of this review involves a literature search of data published on PubMed, abstracts from international conferences, and our own research. Recent evidence suggests that PTCL are 'epigenetic' driven diseases, an observation underscored by a series of clinical and biological observations...
February 20, 2019: Expert Review of Hematology
Hsiling Chiu, Preeti Trisal, Chad Bjorklund, Soraya Carrancio, Estela G Toraño, Carla Guarinos, Despoina Papazoglou, Patrick R Hagner, Asma Beldi-Ferchiou, Karin Tarte, Marie-Hélène Delfau-Larue, Franck Morschhauser, Alan G Ramsay, Anita K Gandhi
Chemotherapy plus rituximab has been the mainstay of treatment for follicular lymphoma (FL) for two decades but is associated with immunosuppression and relapse. In phase 2 studies, lenalidomide combined with rituximab (R2 ) has shown clinical synergy in front-line and relapsed/refractory FL. Here, we show that lenalidomide reactivated dysfunctional T and Natural Killer (NK) cells ex vivo from FL patients by enhancing proliferative capacity and T-helper cell type 1 (Th1) cytokine release. In combination with rituximab, lenalidomide improved antibody-dependent cellular cytotoxicity in sensitive and chemo-resistant FL cells, via a cereblon-dependent mechanism...
February 14, 2019: British Journal of Haematology
Ian W Flinn, Carole B Miller, Kirit M Ardeshna, Scott Tetreault, Sarit E Assouline, Jiri Mayer, Michele Merli, Scott D Lunin, Andrew R Pettitt, Zoltan Nagy, Olivier Tournilhac, Karem-Etienne Abou-Nassar, Michael Crump, Eric D Jacobsen, Sven de Vos, Virginia M Kelly, Weiliang Shi, Lori Steelman, NgocDiep Le, David T Weaver, Stephanie Lustgarten, Nina D Wagner-Johnston, Pier Luigi Zinzani
PURPOSE: Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy...
February 11, 2019: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Su-Kyung Jung, Ji-Sun Paik, Gyeong-Sin Park, Seok-Goo Cho, Suk-Woo Yang
PURPOSE: To report the clinical manifestations of 199 patients with suspected conjunctival lymphoma, the associations between these features and the pathological diagnoses, and the prognosis of conjunctival lesions during long-term follow-up. METHODS: We conducted a retrospective chart review of 199 patients who underwent conjunctival biopsy on suspicion of conjunctival lymphoproliferative disease between January 2008 and June 2015. We focused on slit-lamp findings in the conjunctiva and the pathological diagnoses...
February 1, 2019: British Journal of Ophthalmology
Anthony J Hatswell, William G Sullivan
Where medical interventions are licensed based on only uncontrolled study data (for example a single-arm trial), a common approach for estimating the incremental benefit is to compare the treatment to a 'historical control'; data collected from patients who did not receive the intervention. We illustrate with motivating examples two methods for the creation of historical controls where disease progression and overall survival are typically the key clinically meaningful endpoints. The first method utilises information routinely collected in a clinical trial programme: patients' time to disease progression on their previous line of treatment against which outcomes can be compared...
January 30, 2019: Statistical Methods in Medical Research
Dong Hoon Lee, Go Woon Kim, So Hee Kwon
Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL) with genetic alterations of BCL-2, KMT2B, and KMT6. FL is refractory to conventional chemotherapy and is still incurable in most patients. Thus, new drugs and/or novel combination treatment strategies are needed to further improve FL patient outcome. We investigated the efficacy of the histone deacetylase 6 (HDAC6) inhibitor A452 combined with a Bruton's tyrosine kinase (BTK) inhibitor ibrutinib on NHL and the underlying mechanisms compared with the current clinically tested HDAC6 inhibitor ACY-1215...
January 29, 2019: Molecular Carcinogenesis
Stalin Chellappa, Kushi Kushekhar, Ludvig A Munthe, Geir E Tjønnfjord, Einar M Aandahl, Klaus Okkenhaug, Kjetil Taskén
In chronic lymphocytic leukemia (CLL), signaling through several prosurvival B cell surface receptors activates the PI3K signaling pathway. Idelalisib is a highly selective PI3K (PI3Kδ) isoform-specific inhibitor effective in relapsed/refractory CLL and follicular lymphoma. However, severe autoimmune adverse effects in association with the use of idelalisib in the treatment of CLL, particularly as a first-line therapy, gave indications that idelalisib may preferentially target the suppressive function of regulatory T cells (Tregs)...
January 28, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Anca Prica, Michael Crump
Soon after the anti-CD20 monoclonal antibody rituximab began to change the management of indolent and aggressive B cell lymphomas, development of alternative antibodies - including chemoimmunoconjugates - was undertaken. Among humanized and fully human CD20 antibodies, obinutuzumab has emerged as one antibody that seems to have lived up to the promise of improved efficacy based on in vitro and preclinical experiments. The data available, thus, far establish obinutuzumab's preferred role as the anti-CD20 antibody of choice in chronic lymphocytic leukemia and untreated follicular lymphoma, as well as an important addition to the treatment of rituximab-refractory indolent lymphomas...
January 22, 2019: Leukemia & Lymphoma
Adam Levin, Nirav N Shah
Chimeric antigen receptor modified T (CAR-T) cell therapy against the CD19 antigen has revolutionized the therapeutic landscape for patients with relapsed, refractory B cell non-Hodgkin lymphoma (NHL). Currently there are two FDA approved products (axicabtagene ciloleucel and tisagenlecleucel) for B cell NHL, with several other constructs under clinical investigation. This review will focus on the clinical outcomes, toxicity profile, and differences among candidate CD19 CAR-T cell products for major subtypes of B cell NHL including diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma...
January 16, 2019: American Journal of Hematology
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
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 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 that the cause of relapse in FL would thus significantly ameliorate the tumor therapeutics. In the present study, we show that TRA-1-60-expressing cells are a unique population in FL, 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 in scattered lymphoma cells in FL tissues only as well as in 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, Jiajia Feng, Andreas Betz, Anjali Pandey, Matt Birrell, Janet M Leeds, Kenneth Der, Sabah Kadri, Pin Lu, Jeremy 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. PATIENTS AND METHODS: 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...
February 15, 2019: 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
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