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bortezomib lymphoma

Madeliene Parrott, Simon Rule
Mantle cell lymphoma (MCL) is a rare but often aggressive B-cell non-Hodgkin lymphoma (NHL). Initial therapy can achieve high response rates but invariably patients relapse and die from their disease. Incorporating a maintenance phase into the treatment strategy may prolong remission duration and ultimately prolong survival. Areas covered: The current literature incorporating a maintenance phase into treatment strategies for newly diagnosed and pre-treated MCL patients has been summarized. A literature search was performed using search terms "mantle cell lymphoma", "indolent NHL", "maintenance", "interferon", "rituximab", "lenalidomide", "bortezomib" and "ibrutinib"...
March 9, 2018: Expert Review of Hematology
Jorge J Castillo, Joshua N Gustine, Kirsten Meid, Toni E Dubeau, Patricia Severns, Lian Xu, Guang Yang, Zachary R Hunter, Steven P Treon
Waldenström macroglobulinaemia (WM) is a rare and incurable lymphoma. Comparative studies evaluating the efficacy of primary therapy in symptomatic WM patients have not been performed. In this study, we compared response and survival outcomes in WM patients who received primary therapy with cyclophosphamide-dexamethasone-rituximab (CDR), bortezomib-dexamethasone-rituximab (BDR) and bendamustine-rituximab (Benda-R), as well as maintenance rituximab following primary therapy. Analyses were adjusted for relevant clinical factors associated with response and survival...
February 22, 2018: British Journal of Haematology
Johannes Drach, Huiqiang Huang, Olga Samoilova, Andrew Belch, Charles Farber, André Bosly, Jan Novak, Jan Zaucha, Angela Dascalescu, Udomsak Bunworasate, Zvenyslava Masliak, Kateryna Vilchevskaya, Tadeusz Robak, Lixia Pei, Brendan Rooney, Helgi van de Velde, Franco Cavalli
This post-hoc subanalysis of the LYM-3002 phase 3 study assessed the efficacy and safety of substituting vincristine in rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHOP; n = 42) for bortezomib (VR-CAP; n = 38) in a subgroup of 80 mantle cell lymphoma (MCL) patients aged <60 years who did not receive stem cell transplantation (SCT) despite medical eligibility. Complete response (CR)/unconfirmed CR (CRu) rates were 67 vs. 39% (odds ratio 3.69 [95% CI(confidence interval): 1.31, 10...
January 17, 2018: Leukemia & Lymphoma
Mohamad Bassam Sonbol, Talal Hilal, Amylou C Dueck, Allison C Rosenthal, Christopher R Conley, Heidi E Kosiorek, Brenda F Ginos, Katherine M Gano, Craig S Nichols, Jose F Leis, Patrick B Johnston, Thomas M Habermann, Donald W Northfelt, Peter Leif Bergsagel, David J Inwards, Thomas E Witzig, Stephen M Ansell, Craig B Reeder
In this phase 2 trial, we sought to evaluate the efficacy and safety of rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included rituximab on day 1 with weekly cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m2 IV in a 28-day cycle. Twenty one patients were enrolled on the study. Median age was 69 years (range 51-80) and 17 (81%) patients had two or more prior treatments. Histologies included FL (n = 8), MCL (n = 8), and LPL/WM (n = 5)...
January 10, 2018: Leukemia & Lymphoma
Christopher Dittus, Natalie Grover, Steven Ellsworth, Xianming Tan, Steven I Park
Plasmablastic lymphoma (PBL) is a rare and aggressive form of B-cell non-Hodgkin lymphoma. This subtype of lymphoma has a post-germinal center cell-of-origin called the plasmablast, and the immunophenotype is more consistent with that of a plasma cell than a lymphocyte. Because of these unique features, PBL is notoriously difficult to treat. Case reports and small reviews have evaluated the addition of agents directed against plasma cell disorders in combination with traditional lymphoma-directed regimens. We describe the largest case series to date, with the longest follow-up, evaluating bortezomib in combination with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (V-EPOCH) for the treatment of PBL...
January 5, 2018: Leukemia & Lymphoma
Atsushi Uematsu, Kohki Kido, Erika Manabe, Hiroyuki Takeda, Hirotaka Takahashi, Minoru Hayashi, Yuuki Imai, Tatsuya Sawasaki
Nuclear factor-κB (NF-κB) proteins are transcription factors that play key roles in regulating most immune responses and cell death. Constitutively active NF-κB has been shown to exhibit chemoresistance by inducing anti-apoptosis in tumor cells. Multiple myeloma is known as a constitutive NF-κB activating disease, and the proteasome inhibitor bortezomib is used to treat multiple myeloma and mantle cell lymphoma. We demonstrate here that DANFIN (N,N'-bis-(2,4-dimethyl-phenyl)-ethane-1,2-diamine) functions as an inhibitor of the p65 family proteins and induces chemosensitization to bortezomib in multiple myeloma...
December 25, 2017: Biochemical and Biophysical Research Communications
Suresh Kumar Balasubramanian, Meena Sadaps, Swapna Thota, Mai Aly, Bartlomiej P Przychodzen, Cassandra M Hirsch, Valeria Visconte, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Pure red cell aplasia is an orphan disease, and as such lacks rationally established standard therapies. Most cases are idiopathic; a subset is antibody-mediated. There is overlap between idiopathic cases and those with T-cell large granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas. In each of the aforementioned, the pathogenetic mechanisms may involve autoreactive cytotoxic responses. We selected 62 uniformly diagnosed pure red cell aplasia patients and analyzed their pathophysiologic features and responsiveness to rationally applied first-line and salvage therapies in order to propose diagnostic and therapeutic algorithms that may be helpful in guiding the management of prospective patients, 52% of whom were idiopathic, while the others involved large granular lymphocytic leukemia, thymoma, and B-cell dyscrasia...
February 2018: Haematologica
Ian W Flinn, Dana S Thompson, Ralph V Boccia, Gerald Miletello, Andrew Lipman, Douglas Flora, Daniel Cuevas, Steven W Papish, Jesus G Berdeja
This Phase II trial evaluated the efficacy of bendamustine, bortezomib and rituximab in patients with previously untreated low-grade lymphoma. Eligible patients had low grade lymphoma with no previous systemic disease treatment. Treatment for all patients was given in 28-day cycles for a maximum of 6 cycles. Patients received rituximab 375 mg/m2 intravenously (IV) on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6; bendamustine 90 mg/m2 IV on days 1 and 2; and bortezomib 1·6 mg/m2 IV on days 1, 8 and 15...
February 2018: British Journal of Haematology
Rebecca Kohnken, Jing Wen, Bethany Mundy-Bosse, Kathleen McConnell, Ashleigh Keiter, Leah Grinshpun, Alex Hartlage, Max Yano, Betina McNeil, Nitin Chakravarti, Basem William, James E Bradner, Michael A Caligiuri, Pierluigi Porcu, Anjali Mishra
MicroRNA (miRNA) dysregulation is a hallmark of cutaneous T-cell lymphoma (CTCL), an often-fatal malignancy of skin-homing CD4+ T cells for which there are few effective therapies. The role of microRNAs (miRs) in controlling epigenetic modifier-dependent transcriptional regulation in CTCL is unknown. In this study, we characterize a novel miR dysregulation that contributes to overexpression of the epigenetic reader bromodomain-containing protein 4 (BRD4). We used patient CD4+ T cells to show diminished levels of miR-29b compared with healthy donor cells...
February 15, 2018: Blood
Nabil Yafour, Florence Beckerich, Claude Eric Bulabois, Patrice Chevallier, Étienne Daguindau, Cécile Dumesnil, Thierry Guillaume, Anne Huynh, Stavroula Masouridi Levrat, Anne-Lise Menard, Mauricette Michallet, Cécile Pautas, Xavier Poiré, Aurelie Ravinet, Ibrahim Yakoub-Agha, Ali Bazarbachi
Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory disease or with persistent molecular or radiological (PET-CT scan) residual disease. Within the frame of the 7th annual workshops of the francophone society for bone marrow transplantation and cellular therapy, the working group reviewed the literature in order to elaborate unified guidelines for the prevention and treatment of relapse after allo-HCT...
December 2017: Bulletin du Cancer
Martin Dreyling, Igor Aurer, Sergio Cortelazzo, Olivier Hermine, Georg Hess, Mats Jerkeman, Steven Le Gouill, Vincent Ribrag, Marek Trněný, Carlo Visco, Jan Walewski, Francesco Zaja, Pier Luigi Zinzani
Patients with mantle cell lymphoma (MCL) usually respond to initial combination chemotherapy, but the disease inevitably relapses and often follows an aggressive course. Here, clinical study results published since 2008 for patients with relapsed/refractory MCL were reviewed to compare available evidence for treatment guidance. Most trials identified were non-randomized, phase II studies performed at a limited number of sites, and many evaluated MCL as one of multiple non-Hodgkin lymphoma subtypes. Additional randomized, comparative trials are needed...
November 27, 2017: Leukemia & Lymphoma
Sudjit Luanpitpong, Nawin Chanthra, Montira Janan, Jirarat Poohadsuan, Parinya Samart, Yaowalak U-Pratya, Yon Rojanasakul, Surapol Issaragrisil
Aberrant energy metabolism represents a hallmark of cancer and contributes to numerous aggressive behaviors of cancer cells, including cell death and survival. Despite the poor prognosis of mantle cell lymphoma (MCL), due to the inevitable development of drug resistance, metabolic reprograming of MCL cells remains an unexplored area. Posttranslational modification of proteins via O- GlcNAcylation is an ideal sensor for nutritional changes mediated by O -GlcNAc transferase (OGT) and is removed by O -GlcNAcase (OGA)...
February 2018: Molecular Cancer Therapeutics
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
November 20, 2017: Cell Cycle
Ling-Ling Shi, Yong-Ping Zhai
Over the last decade, bortezomib(BTZ) has been extensively applied in the treatment of hematological malignancies, particularly in multiple myeloma and mantle cell lymphoma, however, the appearence of secondary resistance to BTZ has brought a huge challenge in MM treatment. In the present review, the mechanisms of resistance to bortezomib in MM are summarized, focusing on the action of ubiquitin-proteasome system(UPS), endoplasmin reticulum stress, antophagy, inducible pro-survival signalling and bone marrow microenvironment as well as exploration of the potential therapeutic strategies in the clinical perspective...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
Soham D Puvvada, José Guillen-Rodriguez, Abhijeet Kumar, Lora Inclán, Kara Heard, Xavier I Rivera, Faiz Anwer, Jonathan H Schatz, Daruka Mahadevan, Daniel O Persky
BACKGROUND: Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). PATIENTS AND METHODS: Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
Marisa Granato, Maria Anele Romeo, Mariangela Sara Tiano, Roberta Santarelli, Roberta Gonnella, Maria Saveria Gilardini Montani, Alberto Faggioni, Mara Cirone
KSHV and EBV are gammaherpesviruses strictly linked to human cancers. Even if the majority of cancer cells harbor a latent infection, the few cells that undergo viral replication may contribute to the pathogenesis and maintenance of the virus-associated malignancies. Cytotoxic drugs used for the therapies of cancers harboring virus-infection often have, as side effect, the activation of viral lytic cycle. Therefore it is important to investigate whether they affect viral reactivation and understand the underlying mechanisms involved...
October 12, 2017: Scientific Reports
Nivedita Arora, Arjun Gupta, Navid Sadeghi
Plasmablastic lymphoma (PBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) classically seen in patients infected with the human immunodeficiency virus, but can also be seen in other immunocompromised states such as transplant recipients, autoimmune diseases and the elderly. PBL is generally associated with a poor prognosis despite chemotherapy. There is evidence supporting the use of bortezomib in combination with standard chemotherapy to achieve durable responses in patients with PBL. We describe a patient with acquired immunodeficiency syndrome who presented with rectal pain and bright red blood per rectum...
October 9, 2017: BMJ Case Reports
Koji Izutsu
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by CD5+, CCND1+, and the CCND1-IGH translocation. Although patients with MCL respond, at least temporarily, to conventional chemotherapy, they eventually have a relapse and the prognosis is generally poor. As a primary treatment option for patients with untreated MCL, a rituximab-containing chemotherapy regimen is administered according to the patient's eligibility for high-dose chemotherapy followed by autologous stem cell transplantation (ASCT)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Marisa Granato, Maria Saveria Gilardini Montani, Maria Anele Romeo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Metformin, the most used drug for the treatment of diabetes type 2 patients, has been shown to have anti-cancer properties. In this study, we found that metformin induced apoptosis in Primary Effusion Lymphoma (PEL) cells, an aggressive B cell lymphoma associated with KSHV against which the conventional therapies usually fail. The cytotoxic effect of metformin correlated with intracellular reactive oxygen species reduction, activation of AMPK, the inhibition of pro-survival pathways such as mTOR and STAT3 and the down-regulation of v-FLIP, a latent viral antigen that also plays a pivotal role in PEL cell survival...
December 2017: Cellular Signalling
Thomas A Guerrero-Garcia, Renzo J Mogollon, Jorge J Castillo
Plasmablastic lymphoma (PBL) is a rare and hard to treat disease. With current standard chemotherapeutic regimens, PBL is associated with a median overall survival of 12-15 months. We performed a systematic review of the literature through March 31, 2017 looking for patients with a diagnosis of PBL who were treated with bortezomib, alone or in combination. We identified 21 patients, of which 11 received bortezomib in the frontline setting and 10 received bortezomib in the relapsed setting. Eleven patients were HIV-positive and 10 were HIV-negative...
November 2017: Leukemia Research
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