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https://www.readbyqxmd.com/read/29781323/targeting-the-b-cell-receptor-pathway-a-review-of-current-and-future-therapies-for-non-hodgkin-s-lymphoma
#1
Thomas D Rodgers, Patrick M Reagan
The B-cell receptor (BCR) pathway is a crucial aspect of mature lymphocytes and is maintained in B-cell neoplasms. Many small module inhibitors targeting kinases within the BCR pathway are approved, with others in development, offering alternative treatment options to standard chemoimmunotherapy. Areas Covered: This review covers both approved inhibitors and investigational inhibitors of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), and phosphoinositide-3-kinase (PI3K) in the treatment of B-cell lymphomas...
May 20, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29777163/evolution-of-cll-treatment-from-chemoimmunotherapy-to-targeted-and-individualized-therapy
#2
REVIEW
Jan A Burger, Susan O'Brien
During the past 5 years, a number of highly active novel agents, including kinase inhibitors targeting BTK or PI3Kδ, an antagonist of the antiapoptotic protein BCL-2, and new anti-CD20 monoclonal antibodies, have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). In these exciting times, care is needed to optimally integrate these novel agents into the traditional treatment algorithm without overlooking or compromising the benefits of established treatments, especially chemoimmunotherapy...
May 18, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29773430/surrogate-endpoints-and-risk-adaptive-strategies-in-previously-untreated-follicular-lymphoma
#3
REVIEW
Mayur S Narkhede, Bruce D Cheson
Follicular lymphoma is the second most common subtype of non-Hodgkin lymphoma with an estimated 3.18 cases per 100,000 people. Despite the prolongation of survival with chemoimmunotherapy, variability in response to initial treatment and outcome still exists. Whereas prolonging overall survival is important, it is generally an unreasonable primary endpoint in the front-line setting. The long follow-up needed and the influence of subsequent therapies creates a potential bias. Thus, clinical trials require approximately 5 to 8 years from activation to completion and analysis of outcomes...
May 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29769624/serial-minimal-residual-disease-mrd-monitoring-during-first-line-fcr-treatment-for-cll-may-direct-individualized-therapeutic-strategies
#4
Philip A Thompson, Christine B Peterson, Paolo Strati, Jeff Jorgensen, Michael J Keating, Susan M O'Brien, Alessandra Ferrajoli, Jan A Burger, Zeev Estrov, Nitin Jain, Tapan M Kadia, Gautam Borthakur, Courtney D DiNardo, Naval Daver, Elias Jabbour, William G Wierda
Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end of therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10-4 ). Eighteen percent of patients had U-MRD after C3 and 48% at EOT...
April 17, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29761908/rituximab-maintenance-therapy-of-follicular-lymphoma-in-clinical-practice
#5
Ulrich Dührsen, Stefanie Broszeit-Luft, Annette Dieing, Andreas Lück, Piotr Porowski, Marcel Reiser, Ulrike Schwinger, Sandra Klawitter, Katja Krumm, Kathleen Jentsch-Ullrich
Standard of care for patients with symptomatic, advanced-stage follicular lymphoma (FL) is rituximab-containing chemoimmunotherapy followed by rituximab maintenance. This prospective, multicenter, noninterventional study analyzed how efficacy and safety data from randomized controlled trials translate into clinical practice in Germany. Both treatment-naïve and relapsed/refractory patients with FL, who responded to rituximab-containing induction and were scheduled for rituximab maintenance, were observed for 24 months...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29749320/combined-treatment-for-gastric-cancer-immunological-approach
#6
Olzhas Zhandossov, Galina Kaussova, Avraam Koten
BACKGROUND/AIMS: Gastric cancer is one of the most common oncological diseases. It can develop in any part of the stomach and spread to other organs, especially the esophagus, lungs, and liver. The aim of our study was to investigate the effectiveness of our proposed therapy. MATERIALS AND METHODS: Our research promises more effective neoadjuvant therapy, including immunotherapy and multi-agent chemotherapy. Of the 62 patients involved in our study, 32 underwent neoadjuvant chemotherapy in combination with surgery, whereas the rest underwent neoadjuvant chemoimmunotherapy with surgery...
March 2018: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/29744624/a-rare-case-of-paediatric-primary-central-nervous-system-lymphoma-treated-with-high-dose-methotrexate-and-rituximab-based-chemoimmunotherapy-and-whole-brain-radiotherapy-followed-by-tumour-bed-boost-with-three-dimensional-conformal-radiation-technique
#7
Narayan Adhikari, Ahitagni Biswas, Sameer Bakhshi, Gaurav Khanna, Vaishali Suri
BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare in the paediatric population. CLINICAL CASE: A 12-year-old boy presented to our clinic with complaints of multiple episodes of generalised tonic-clonic seizures for 1 year and gradual loss of vision in both eyes for 3 months. Baseline magnetic resonance imaging (MRI) of the brain showed a large (7.2 × 7 cm) enhancing soft tissue lesion in the right frontal lobe causing mass effect and midline shift...
May 9, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29742083/update-on-signal-inhibitors-in-chronic-lymphocytic-leukemia
#8
Prajwal Boddu, Nitin Jain
The last decade has seen major progress in our understanding of the pathobiology of chronic lymphocytic leukemia (CLL) and the identification of potential new therapeutic targets. As a result, researchers have developed novel targeted therapies, several of which are already approved and many of which are in advanced stages of clinical development. These new agents are much less toxic than chemoimmunotherapy and may be preferred for their superior efficacy in patients with certain high-risk features, such as del(17p)...
April 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29728204/chronic-lymphocytic-leukemia-diagnosis-and-treatment
#9
REVIEW
Paolo Strati, Nitin Jain, Susan O'Brien
The complexity of the treatment of patients with chronic lymphocytic leukemia has increased substantially over the past several years as a consequence of the advent of novel biological agents such as ibrutinib, idelalisib, and venetoclax, as well as increasingly potent anti-CD20 monoclonal antibodies. In addition, the identification of molecular predictive markers and the introduction of more sensitive and sophisticated techniques to assess minimal residual disease have allowed optimization of the use of chemoimmunotherapy and targeted therapies and may become standard of care in the future...
May 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29675465/elimination-of-established-tumors-with-nanodisc-based-combination-chemoimmunotherapy
#10
Rui Kuai, Wenmin Yuan, Sejin Son, Jutaek Nam, Yao Xu, Yuchen Fan, Anna Schwendeman, James J Moon
Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein-mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29674504/efficacy-of-bendamustine-and-rituximab-as-first-salvage-treatment-in-chronic-lymphocytic-leukemia-and-indirect-comparison-with-ibrutinib-a-gimema-eric-and-uk-cll-forum-study
#11
Antonio Cuneo, George Follows, Gian Matteo Rigolin, Alfonso Piciocchi, Alessandra Tedeschi, Livio Trentin, Angeles Medina Perez, Marta Coscia, Luca Laurenti, Gerardo Musuraca, Lucia Farina, Alfredo Rivas Delgado, Ester Maria Orlandi, Piero Galieni, Francesca Romana Mauro, Carlo Visco, Angela Amendola, Atto Billio, Roberto Marasca, Annalisa Chiarenza, Vittorio Meneghini, Fiorella Ilariucci, Monia Marchetti, Stefano Molica, Francesca Re, Gianluca Gaidano, Marcos Gonzalez, Francesco Forconi, Stefania Ciolli, Agostino Cortelezzi, Marco Montillo, Lukas Smolej, Anna Schuh, Toby A Eyre, Ben Kennedy, Kris M Bowles, Marco Vignetti, Javier de la Serna, Carol Moreno, Robin Foà, Paolo Ghia
We performed an observational study on the efficacy of bendamustine and rituximab as first salvage regimen in chronic lymphocytic leukemia. In an intention-to-treat analysis including 237 patients, the median progression free survival was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter progression free survival at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis...
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29669928/cx3cr1-identifies-pd-1-therapy-responsive-cd8-t-cells-that-withstand-chemotherapy-during-cancer-chemoimmunotherapy
#12
Yiyi Yan, Siyu Cao, Xin Liu, Susan M Harrington, Wendy E Bindeman, Alex A Adjei, Jin Sung Jang, Jin Jen, Ying Li, Pritha Chanana, Aaron S Mansfield, Sean S Park, Svetomir N Markovic, Roxana S Dronca, Haidong Dong
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti-PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of chemotherapy and are increased in patients with metastatic melanoma who responded to chemoimmunotherapy (paclitaxel and carboplatin plus PD-1 blockade)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29651351/acquired-von-willebrand-disease-associated-with-mantle-cell-lymphoma
#13
Dominique Maas, Britta Laros-van Gorkom, Sanne Gianotten, Marjan Cruijsen, Waander van Heerde, Marten Nijziel
We present a rare case of acquired von Willebrand syndrome (AVWS) caused by a mantle cell lymphoma. A 61-year-old male suffered from recurrent bleeding symptoms since a few months. Initially, physical examination was normal. von Willebrand factor antigen (VWF:Ag) level and factor VIII activity (FVIII:C) were low (0.31 IU/ml and 0.43 IU/ml, resp.). Ristocetin cofactor activity (VWF:RCo) was 0.09 IU/ml, and collagen binding activity (VWF:CB) was 0.10 IU/ml. VWF:RCo/VWF:Ag ratio was 0.29, and RIPA value was normal...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29645093/autologous-transplantation-versus-allogeneic-transplantation-in-patients-with-follicular-lymphoma-experiencing-early-treatment-failure
#14
Sonali M Smith, James Godfrey, Kwang Woo Ahn, Alyssa DiGilio, Sairah Ahmed, Vaibhav Agrawal, Veronika Bachanova, Ulrike Bacher, Asad Bashey, Javier Bolaños-Meade, Mitchell Cairo, Andy Chen, Saurabh Chhabra, Edward Copelan, Parastoo B Dahi, Mahmoud Aljurf, Umar Farooq, Siddhartha Ganguly, Mark Hertzberg, Leona Holmberg, David Inwards, Abraham S Kanate, Reem Karmali, Vaishalee P Kenkre, Mohamed A Kharfan-Dabaja, Andreas Klein, Hillard M Lazarus, Matthew Mei, Alberto Mussetti, Taiga Nishihori, Praveen Ramakrishnan Geethakumari, Ayman Saad, Bipin N Savani, Harry C Schouten, Nirav Shah, Alvaro Urbano-Ispizua, Ravi Vij, Julie Vose, Anna Sureda, Mehdi Hamadani
BACKGROUND: Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. METHODS: This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014...
April 12, 2018: Cancer
https://www.readbyqxmd.com/read/29644450/monitoring-and-management-of-toxicities-of-novel-b-cell-signaling-agents
#15
REVIEW
Joanna Rhodes, Anthony Mato, Jeff P Sharman
PURPOSE REVIEW: B cell signaling agents, including ibrutinib, idelalisib, and the BCL-2 inhibitor venetoclax have become an integral part of therapy for patients with non-Hodgkin's lymphomas. The toxicity profiles of these medications is distinct from chemoimmunotherapy. Here, we will review the mechanism of action of these drugs, their efficacy, and toxicity management. RECENT FINDINGS: Ibrutinib use is associated with increased risk of atrial fibrillation and bleeding which can be managed using dose interruptions and modifications...
April 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29618689/-osteonecrosis-developing-after-rituximab-containing-chemotherapy-for-waldenstr%C3%A3-m-macroglobulinemia
#16
Fumihiko Nakamura, Risen Hirai, Takashi Higo, Tomiteru Togano, Rieko Sekine
A 71-year-old woman presented with fever, weight loss, and anemia because of recurrent Waldenström macroglobulinemia (WM) with cryoglobulinemia. Treatment with five cycles of doxorubicin, vincristine, cyclophosphamide, and prednisolone (CHOP) therapy was initiated, which resulted in insufficient improvement in anemia. Hence, a combination of rituximab and CHOP therapy was subsequently initiated. The patient complained of lumbago and lower leg pain on day 4 of the chemoimmunotherapy. X-ray findings for the affected sites were unremarkable, and the patient's symptoms gradually and spontaneously subsided...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29605154/prognostication-of-diffuse-large-b-cell-lymphoma-in-the-molecular-era-moving-beyond-the-ipi
#17
REVIEW
Joel C Wight, Geoffrey Chong, Andrew P Grigg, Eliza A Hawkes
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. Despite the majority of patients being cured with combination chemoimmunotherapy, up to 30% eventually succumb to the disease. Until recently, baseline prognostic assessment has centred on the International Prognostic Index (IPI), although this index is yet to impact strongly on treatment choice. Molecular features such as cell of origin, MYC and BCL-2 genetic alterations and protein overexpression were identified over a decade ago, yet their prognostic value is still not fully elucidated...
March 26, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29596546/rituximab-maintenance-therapy-after-first-line-induction-chemoimmunotherapy-for-follicular-lymphoma
#18
Talal Hilal, Jose F Leis, Craig B Reeder
Clinical Question: Is rituximab maintenance therapy after first-line induction chemoimmunotherapy for follicular lymphoma associated with improved outcomes? Bottom Line: Compared with observation, rituximab maintenance therapy prolongs progression-free survival without an improvement in overall survival or quality of life after first-line induction chemoimmunotherapy.
March 29, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29571669/chronic-lymphocytic-leukemia-and-infection-risk-in-the-era-of-targeted-therapies-linking-mechanisms-with-infections
#19
REVIEW
Talal Hilal, Juan C Gea Banacloche, Jose F Leis
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the world. Patient with CLL are at particular risk for infections due to inherent disease-related immune dysfunction in addition to the effect of certain systemic therapies on the immune system. The advent of B-cell receptor (BCR) inhibitors such as ibrutinib and idelalisib has led to a practice change that utilizes these targeted agents in the treatment of CLL, either in place of chemoimmunotherapy (CIT) or in later line settings. In this paper, we review the pathophysiology of immune dysfunction in CLL, the spectrum of immunodeficiency with the various therapeutic agents along with prevention strategies with a focus on targeted therapies...
March 16, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29558107/tumor-ablation-and-therapeutic-immunity-induction-by-an-injectable-peptide-hydrogel
#20
Honglin Jin, Chao Wan, Zhenwei Zou, Guifang Zhao, Lingling Zhang, Yuanyuan Geng, Tong Chen, Ai Huang, Fagang Jiang, Jue-Ping Feng, Jonathan F Lovell, Jing Chen, Gang Wu, Kunyu Yang
Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells...
March 20, 2018: ACS Nano
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