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refractory non hodgkin lymphoma

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https://www.readbyqxmd.com/read/28220479/a-phase-1-2-trial-of-ublituximab-a-novel-anti-cd20-monoclonal-antibody-in-patients-with-b-cell-non-hodgkin-lymphoma-or-chronic-lymphocytic-leukaemia-previously-exposed-to-rituximab
#1
Ahmed Sawas, Charles M Farber, Marshall T Schreeder, Mazen Y Khalil, Daruka Mahadevan, Changchun Deng, Jennifer E Amengual, Petros G Nikolinakos, Jill M Kolesar, John G Kuhn, Peter Sportelli, Hari P Miskin, Owen A O'Connor
This phase 1/2 study evaluated the safety, pharmacokinetic behavior and anti-tumour activity of ublituximab, a unique type I, chimeric, glycoengineered anti-CD20 monoclonal antibody, in rituximab-relapsed or -refractory patients with B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukaemia (CLL). Induction therapy (doses of 450-1200 mg) consisted of 4 weekly infusions in cycle 1 for NHL and 3 weekly infusions in cycles 1 and 2 for CLL. Patients received ublituximab maintenance monthly during cycles 3-5, then once every 3 months for up to 2 years...
February 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28211162/efficacy-of-the-oral-mtorc1-inhibitor-everolimus-in-relapsed-or-refractory-indolent-lymphoma
#2
N Nora Bennani, Betsy R LaPlant, Stephen M Ansell, Thomas M Habermann, David J Inwards, Ivana N Micallef, Patrick B Johnston, Luis F Porrata, Joseph P Colgan, Svetomir N Markovic, Grzegorz S Nowakowski, William R Macon, Craig B Reeder, Joseph R Mikhael, Donald W Northfelt, Irene M Ghobrial, Thomas E Witzig
Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas...
February 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28203344/emerging-role-of-checkpoint-blockade-therapy-in-lymphoma
#3
REVIEW
Natalie Galanina, Justin Kline, Michael R Bishop
Following the successful application of immune checkpoint blockade therapy (CBT) in refractory solid tumors, it has recently gained momentum as a promising modality in the treatment of relapsed lymphoma. This significant therapeutic advance stems from decades of research that elucidated the role of immune regulation pathways and the mechanisms by which tumors can engage these critical pathways to escape immune detection. To date, two main pathways, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1), have emerged as key targets of CBT demonstrating unprecedented activity particularly in heavily pretreated relapsed/refractory Hodgkin lymphoma and some forms of non-Hodgkin disease...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28194058/l-probe-a-novel-non-anthracycline-combination-chemotherapy-regimen-for-aggressive-b-cell-non-hodgkin-lymphoma-in-elderly-patients
#4
Arjun Datt Law, Gaurav Prakash, Alka Khadwal, Ashim Das, Subhash Varma, Pankaj Malhotra
The management of aggressive B cell lymphomas in elderly patients is associated with poor tolerability of commonly used chemotherapeutic agents. The safety and tolerability of a novel combination chemotherapy regimen utilizing rituximab, lenalidomide, bendamustine, vincristine and prednisolone was assessed in a series of elderly patients with new onset or relapsed/refractory aggressive B cell lymphoma and inability to receive conventional chemotherapy due to poor performance status and/or significant comorbidities...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28168350/allogeneic-hematopoietic-stem-cell-transplantation-for-non-hodgkin-s-lymphomas-a-retrospective-analysis-of-77-cases
#5
Ana M Picleanu, Silvana Novelli, Anna Monter, Irene Garcia-Cadenas, Ana C Caballero, Rodrigo Martino, Albert Esquirol, Javier Briones, Jorge Sierra
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for relapsed, advanced, and otherwise incurable non-Hodgkin's lymphomas (NHL) suggested by the existence of a graft-versus-lymphoma effect. The main complications are graft-versus-host disease and infections. We performed a retrospective analysis of patients with NHL, who received an allo-SCT between January 1995 and December 2014. The parameters that had an impact on overall survival were age ≤60 years old, chemosensitive disease pre-allo-SCT, and indolent NHL histology...
February 6, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28137826/anti-cd20-interleukin-21-fusokine-targets-malignant-b-cells-via-direct-apoptosis-and-nk-cell-dependent-cytotoxicity
#6
Shruti Bhatt, Salma Parvin, Yu Zhang, Hyun-Mi Cho, Kranthi Kunkalla, Francisco Vega, John M Timmerman, Seung-Uon Shin, Joseph D Rosenblatt, Izidore S Lossos
In spite of newly emerging therapies and the improved survival of non-Hodgkin lymphoma (NHL) patients, relapses or primary refractory disease are commonly observed and associated with dismal prognosis. While discovery of the anti-CD20 antibody rituximab has markedly improved outcomes in B-cell NHL, rituximab resistance remains an important obstacle to successful treatment of these tumors. To improve the efficacy of CD20-targeted therapy, we fused IL-21, which induces direct lymphoma cytotoxicity and activates immune effector cells, to the anti-CD20 antibody (αCD20-IL-21 fusokine)...
January 30, 2017: Blood
https://www.readbyqxmd.com/read/28134921/improving-outcomes-after-allogeneic-hematopoietic-cell-transplantation-for-hodgkin-lymphoma-in-the-brentuximab-vedotin-era
#7
L Hegerova, Q Cao, A Lazaryan, B L McClune, D J Weisdorf, C G Brunstein, V Bachanova
Allogeneic hematopoietic cell transplantation (alloHCT) remains a valuable treatment alternative for relapsed/refractory (R/R) Hodgkin lymphoma (HL). Data on alloHCT outcomes in the era of new HL therapies are needed. We evaluated 72R/R HL patients who received reduced intensity conditioning alloHCT and compared the time periods 2009-2013 (n=20) with 2000-2008 (n=52). Grafts included HLA-matched sibling (35%), unrelated donor (8%) and umbilical cord blood (56%). In the recent period, patients more often received brentuximab vedotin (BV, 60% vs 2%), had fewer comorbidities (Sorror index 0: 60% vs 12%) and were in complete remission (50% vs 23%)...
January 30, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28126962/safety-and-efficacy-of-abexinostat-a-pan-histone-deacetylase-inhibitor-in-non-hodgkin-lymphoma-and-chronic-lymphocytic-leukemia-results-of-a-phase-2-study
#8
Vincent Ribrag, Won Seog Kim, Reda Bouabdallah, Soon Thye Lim, Bertrand Coiffier, Arpad Illes, Bernard Lemieux, Martin J S Dyer, Fritz Offner, Zakia Felloussi, Ioana Kloos, Ying Luan, Remus Vezan, Thorsten Graef, Franck Morschhauser
Histone deacetylase inhibitors are members of a class of epigenetic drugs that have proven activity in T-cell malignancies, but little is known about their efficacy in B-cell lymphomas. Abexinostat is an orally available hydroxamate-containing histone deacetylase inhibitor that differs from approved inhibitors; its unique pharmacokinetic profile and oral dosing schedule, twice daily 4 hours apart, allows for continuous exposure at concentrations required for efficient tumor cell killing. In this phase 2 study, patients with relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia received oral abexinostat at 80 mg BID for 14 days of a 21-day cycle and continued until progressive disease or unacceptable toxicity...
January 25, 2017: Haematologica
https://www.readbyqxmd.com/read/28123744/complete-response-to-azacitidine-priming-and-nab-paclitaxel-in-non-hodgkin-lymphoma-resistant-to-biochemotherapy
#9
Randy C Bowen, Andrew W Hahn, Thomas W Butler, Hung T Khong
The standard of care for first-line therapy in diffuse large B-cell lymphoma (DLBCL) is the rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) regimen. For patients who fail to respond, have an incomplete response or relapse, numerous effective options exists besides salvage cisplatin-based regimen and autologous stem cell therapy. Even with this approach, the outcome remains very poor for this group of patients. The present case illustrates a 55-year-old woman diagnosed with DLBCL, who experienced an early incomplete response, later progression during treatment with the R-CHOP regimen...
January 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28118604/tenovin-6-inhibits-proliferation-and-survival-of-diffuse-large-b-cell-lymphoma-cells-by-blocking-autophagy
#10
Hongfeng Yuan, Meilan He, Fan Cheng, Rosemary Bai, Suzane Ramos da Silva, Ricardo C T Aguiar, Shou-Jiang Gao
Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive non-Hodgkin lymphomas. It is curable but one-third of cases are refractory to therapy or relapse after initial response highlighting the urgent need for developing novel therapeutic approaches. Targeting sirtuins, particularly SIRT1 by genetic approaches or using pharmaceutical inhibitor tenovin-6, has shown promising therapeutic potential in various hematopoietic malignancies. However, it remains unknown whether these approaches are effective for DLBCL...
January 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28110394/chimeric-antigen-receptor-car-t-cells-lessons-learned-from-targeting-of-cd19-in-b-cell-malignancies
#11
Kevin A Hay, Cameron J Turtle
Adoptive immunotherapy with chimeric antigen receptor-modified (CAR)-T cells is a rapidly growing therapeutic approach to treating patients with refractory cancer, with over 100 clinical trials in various malignancies in progress. The enthusiasm for CAR-T cells has been driven by the clinical success of CD19-targeted CAR-T cell therapy in B-cell acute lymphoblastic leukemia, and the promising data in B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Despite the success of targeting CD19 with CAR-T cells in early clinical studies, many challenges remain to improve outcomes, reduce toxicity, and determine the appropriate settings for CAR-T cell immunotherapy...
January 21, 2017: Drugs
https://www.readbyqxmd.com/read/28095146/phase-i-first-in-human-study-of-venetoclax-in-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma
#12
Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A Humerickhouse, Gary B Gordon, John F Gerecitano
Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts...
January 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28094575/treatment-approaches-of-hard-to-treat-non-hodgkin-lymphomas
#13
Lakshminarayanan Nandagopal, Amitkumar Mehta
Even after recent advancements with monoclonal antibodies, antibody drug conjugates and immune therapies, relapsed and refractory lymphomas remain challenging to treat; and the definition and treatment approaches of hard-to-treat lymphomas (HTL) continue to evolve. Areas covered: In this review, we will address HTL encompassing diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and peripheral T cell lymphomas (PTCL). DLBCL, which comprises 30-40% of non-Hodgkin lymphomas is a highly aggressive and heterogeneous malignancy, with primary refractory or relapsed disease remaining a therapeutic challenge...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28067872/reduced-intensity-and-non-myeloablative-allogeneic-stem-cell-transplantation-from-alternative-hla-mismatched-donors-for-hodgkin-lymphoma-a-study-by-the-french-society-of-bone-marrow-transplantation-and-cellular-therapy
#14
J Gauthier, L Castagna, F Garnier, T Guillaume, G Socié, S Maury, N Maillard, R Tabrizi, T Marchand, J Malfuson, A Gac, E Gyan, M Mercier, Y Béguin, J Delage, P Turlure, A Marçais, S Nguyen, R Dulery, J Bay, A Huynh, E Daguindau, J Cornillon, C Régny, M Michallet, R Peffault de Latour, I Yakoub-Agha, D Blaise
Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28067179/cd20-based-immunotherapy-of-b-cell-derived-hematologic-malignancies
#15
Dariush Shanehbandi, Jafar Majidi, Tohid Kazemi, Behzad Baradaran, Leili Aghebati-Maleki
CD20 is a surface antigen which is expressed at certain stages of B-cell differentiation. Targeting the CD20-positive B-cells with therapeutic monoclonal antibodies (MAbs) has been an effectual strategy in the treatment of hematologic malignancies such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Initial success with Rituximab (RTX) has encouraged the creation and development of more effective CD20 based therapeutics. However, treatment with conventional MAbs has not been adequate to overcome the problems such as refractory/relapsed disease...
January 9, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28040682/t-cell-lymphoma-recent-advances-in-characterization-and-new-opportunities-for-treatment
#16
REVIEW
Carla Casulo, Owen O'Connor, Andrei Shustov, Michelle Fanale, Jonathan W Friedberg, John P Leonard, Brad S Kahl, Richard F Little, Lauren Pinter-Brown, Ranjani Advani, Steven Horwitz
Peripheral T-cell lymphomas (PTCLs) are uncommon, heterogeneous, and aggressive non-Hodgkin's lymphomas. Despite progress in the last several years resulting in a deeper understanding of PTCL biology and pathogenesis, there is currently no accepted single standard of care for newly diagnosed patients, and for those with relapsed or refractory disease, prognosis is dismal. The National Cancer Institute convened a Clinical Trials Planning Meeting to advance the national clinical trial agenda in lymphoma. The objective was to identify unmet needs specific to five major lymphoma subtypes and develop strategies to address them...
February 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28024487/-clinical-efficacy-of-autologous-hematopoietic-stem-cell-transplantation-using-tumor-ablative-conditioning-regimen-for-patients-with-refractory-relapsed-non-hodgkin-s-lymphoma
#17
Xue-Liang Yang, Ya-Mei Wu, Yong-Bin Cao, Xiao-Hong Li, Li-Xin Xu, Zhou-Yang Liu, Bei Liu, Bei Yan, Song-Wei Li, Wan-Ming DA, Xiao-Xiong Wu
OBJECTIVE: To investigate the safety and effectiveness of autologous hematopoietic stem cell transplantation (auto-HSCT) using tumor-ablative conditioning regiment for patients with refractory/relapsed non-Hodgkin's lymphoma. METHODS: The clinical data of 16 patients with refractory/relapsed non-Hodgkin's lymphoma received above-mentioned therapeutic regimen from January 2013 to July 2015 was analyzed retrospectively, and conditioning-related toxicity, engraftment, infection, relapse and survival rate were evaluated...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28007754/myeloablative-versus-reduced-intensity-allogeneic-stem-cell-transplantation-for-relapsed-refractory-hodgkin-s-lymphoma-in-recent-years-a-retrospective-analysis-of-the-lymphoma-working-party-of-the-european-group-for-blood-and-marrow-transplantation
#18
S Genadieva-Stavrik, A Boumendil, P Dreger, K Peggs, J Briones, P Corradini, A Bacigalupo, G Socié, F Bonifazi, H Finel, A Velardi, M Potter, B Bruno, L Castagna, R Malladi, N Russell, A Sureda
BACKGROUND: To evaluate long-term outcome of myeloablative allogeneic stem cell transplantation (allo-SCT) (MAC) versus reduced-intensity allo-SCT (RIC) in patients with relapsed/refractory Hodgkin's lymphoma (HL) in recent years. PATIENTS AND METHODS: A total of 312 patients (63 MAC and 249 RIC) with relapsed/refractory HL who received allo-SCT between 2006 and 2010 and were reported to the EBMT Database were included in the study. RESULTS: With a median follow-up for alive patients of 56 (26-73) months, there were no significant differences in non-relapse mortality (NRM) between MAC and RIC...
December 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28004361/a-review-of-obinutuzumab-ga101-a-novel-type-ii-anti-cd20-monoclonal-antibody-for-the-treatment-of-patients-with-b-cell-malignancies
#19
REVIEW
Kensei Tobinai, Christian Klein, Naoko Oya, Günter Fingerle-Rowson
Obinutuzumab (GA101) is a novel, type II, glycoengineered, humanized anti-CD20 monoclonal antibody that has been developed to address the need for new therapeutics with improved efficacy in patients with lymphocytic leukemia and lymphoma of B-cell origin. Obinutuzumab has a distinct mode of action relative to type I anti-CD20 antibodies, such as rituximab, working primarily by inducing direct cell death and antibody-dependent cell-mediated cytotoxicity. Obinutuzumab is under investigation in a wide-ranging program of clinical trials in patients with B-cell malignancies...
December 21, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27981793/responses-to-romidepsin-by-line-of-therapy-in-patients-with-relapsed-or-refractory-peripheral-t-cell-lymphoma
#20
Francine Foss, Barbara Pro, H Miles Prince, Lubomir Sokol, Dolores Caballero, Steven Horwitz, Bertrand Coiffier
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas typically associated with poor prognosis. Most patients with PTCL receive chemotherapy as first-line treatment, but many experience rapid relapse. For patients with relapsed/refractory PTCL, responses to treatment and long-term outcomes tend to worsen with increasing lines of therapy. Romidepsin is a potent class I histone deacetylase inhibitor approved by the US Food and Drug Administration for the treatment of PTCL in patients who have received ≥1 prior therapy...
January 2017: Cancer Medicine
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