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Marco Ruella, Marcela V Maus
Immunotherapy is the revolution in cancer treatment of this last decade. Among multiple approaches able to harness the power of the immune system against cancer, T cell based immunotherapies represent one of the most successful examples. In particular, biotechnological engineering of protein structures, like the T cell receptor or the immunoglobulins, allowed the generation of synthetic peptides like chimeric antigen receptors and bispecific antibodies that are able to redirect non-tumor specific T cells to recognize and kill leukemic cells...
2016: Computational and Structural Biotechnology Journal
Xavier Thomas, Caroline Le Jeune
Advances in acute lymphocytic leukemia (ALL) therapy has led to long-term survival rates in children. However, only 30%-40% of adults achieve long-term disease-free survival. After relapse, the outcome of salvage chemotherapy is very disappointing with less than 10% of long survival. Novel agents are therefore desperately required to improve response rates and survival, but also the quality of life of patients. Areas covered. The following review is a comprehensive summary of various novel options reported over the past few years in the therapeutic area of adult ALL...
October 19, 2016: Expert Opinion on Pharmacotherapy
(no author information available yet)
Blinatumomab was active across age and risk groups in patients with relapsed or refractory BCP-ALL.
October 14, 2016: Cancer Discovery
Lindsay Hladnik, Kristan Augustin, Sean DeFrates
No abstract text is available yet for this article.
January 2016: Journal of the Advanced Practitioner in Oncology
Judith Feucht, Simone Kayser, David Gorodezki, Mohamad Hamieh, Michaela Döring, Franziska Blaeschke, Patrick Schlegel, Hans Bösmüller, Leticia Quintanilla-Fend, Martin Ebinger, Peter Lang, Rupert Handgretinger, Tobias Feuchtinger
T-cell immunotherapies are promising options in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We investigated the effect of co-signaling molecules on T-cell attack against leukemia mediated by CD19/CD3-bispecific T-cell engager. Primary CD19+ ALL blasts (n≥10) and physiologic CD19+CD10+ bone marrow precursors were screened for 20 co-signaling molecules. PD-L1, PD-1, LAG-3, CD40, CD86, CD27, CD70 and HVEM revealed different stimulatory and inhibitory profiles of pediatric ALL compared to physiologic cells, with PD-L1 and CD86 as most prominent inhibitory and stimulatory markers...
September 30, 2016: Oncotarget
Nikolaos Papadantonakis, Anjali S Advani
This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells...
October 2016: Therapeutic Advances in Hematology
Francisco Bautista, Jasper Van der Lugt, Pamela R Kearns, Francis J Mussai, C Michel Zwaan, Lucas Moreno
Survival rates in pediatric leukemia have greatly improved in the last decades but still a substantial number of patients will relapse and die. New agents are necessary to overcome the limitations of conventional chemotherapy and hematopoietic stem cell transplantation and to reduce their undesirable long-term toxicities. The identification of driving molecular alterations of leukemogenesis in subsets of patients will allow the incorporation of new-targeted therapies. Areas covered: In this article the authors present a detailed review of the most recent advances in targeted therapies for pediatric leukemias...
November 2016: Expert Opinion on Drug Discovery
Samantha DePadova, Christina Howlett, Kimberly Rivera
Blinatumomab (Blincyto®) has received accelerated approval for treatment of relapsed or refractory acute lymphoblastic leukemia. This article describes the authors' experience with a multidisciplinary collaboration among nursing, pharmacy, prescribers, and support staff, which has proven to be key for safe administration. The approach can be applied to other institutions planning to use blinatumomab.
October 1, 2016: Clinical Journal of Oncology Nursing
N Gökbuget, M Kelsh, V Chia, A Advani, R Bassan, H Dombret, M Doubek, A K Fielding, S Giebel, V Haddad, D Hoelzer, C Holland, N Ifrah, A Katz, T Maniar, G Martinelli, M Morgades, S O'Brien, J-M Ribera, J M Rowe, A Stein, M Topp, M Wadleigh, H Kantarjian
We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial...
2016: Blood Cancer Journal
Elias Jabbour, Nicholas J Short, Jeffrey L Jorgensen, Musa Yilmaz, Farhad Ravandi, Sa A Wang, Deborah A Thomas, Joseph Khoury, Richard E Champlin, Issa Khouri, Partow Kebriaei, Susan M O'Brien, Guillermo Garcia-Manero, Jorge E Cortes, Koji Sasaki, Courtney D Dinardo, Tapan M Kadia, Nitin Jain, Marina Konopleva, Rebecca Garris, Hagop Kantarjian
BACKGROUND: Minimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear. METHODS: This study identified 78 patients with relapsed/refractory B-cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini-hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission...
September 7, 2016: Cancer
Kum Ja Lee, Vivian Chow, Ashley Weissman, Sunil Tulpule, Ibrahim Aldoss, Mojtaba Akhtari
Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated...
2016: Therapeutics and Clinical Risk Management
Marco Ruella, David M Barrett, Saad S Kenderian, Olga Shestova, Ted J Hofmann, Jessica Perazzelli, Michael Klichinsky, Vania Aikawa, Farzana Nazimuddin, Miroslaw Kozlowski, John Scholler, Simon F Lacey, Jan J Melenhorst, Jennifer J D Morrissette, David A Christian, Christopher A Hunter, Michael Kalos, David L Porter, Carl H June, Stephan A Grupp, Saar Gill
Potent CD19-directed immunotherapies, such as chimeric antigen receptor T cells (CART) and blinatumomab, have drastically changed the outcome of patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). However, CD19-negative relapses have emerged as a major problem that is observed in approximately 30% of treated patients. Developing approaches to preventing and treating antigen-loss escapes would therefore represent a vertical advance in the field. Here, we found that in primary patient samples, the IL-3 receptor α chain CD123 was highly expressed on leukemia-initiating cells and CD19-negative blasts in bulk B-ALL at baseline and at relapse after CART19 administration...
October 3, 2016: Journal of Clinical Investigation
Max S Topp, Zachary Zimmerman, Hagop M Kantarjian
No abstract text is available yet for this article.
October 2016: Nature Reviews. Clinical Oncology
Jacqueline B Stone, Lisa M DeAngelis
No abstract text is available yet for this article.
October 2016: Nature Reviews. Clinical Oncology
Muhammad Waqas Khan, Zartash Gul
Blinatumomab, a bispecific T-cell engager monoclonal antibody used to manage Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) can be used to treat patients by inducing graft versus leukemia reaction post allogeneic hematopoietic stem cell transplantation, a feature which it was post allogeneic bone marrow transplantation, a feature which this drug was not aimed to do.
August 2016: Clinical Case Reports
Nosha Farhadfar, Mark R Litzow
Monoclonal antibodies represent a major advance in treatment of acute lymphoblastic leukemia (ALL). Targeted delivery of these agents based on leukemic cell-surface receptor recognition, improves efficacy and minimizes off-target toxicity. The antigens CD19, CD20, CD22 and CD52, are the most common antigens to which monoclonal antibodies in B-cell ALL have been directed. Rituximab, an anti-CD20 antibody, in combination with conventional chemotherapy has been shown to improve survival in newly diagnosed CD20 positive B-cell ALL...
October 2016: Leukemia Research
Stephanie A Folan, Amber Rexwinkle, Jane Autry, Jeffrey C Bryan
Adult patients with acute lymphoblastic leukemia who relapse after frontline therapy have extremely poor outcomes despite advances in chemotherapy and hematopoietic stem cell transplantation. Blinatumomab is a first-in-class bispecific T-cell engager that links T cells to tumor cells leading to T-cell activation and tumor cell lysis. In December 2014, the Food and Drug Administration approved blinatumomab for treatment of relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
Elisa Becze
No abstract text is available yet for this article.
June 2016: ONS Connect
Mohammed Alcharakh, Seongseok Yun, Yimin Dong, Nicole D Vincelette, Madiha Daud, Saima Manzoor, Irbaz Bin Riaz, Faiz Anwer
Post-stem cell transplantation (SCT) relapsed acute lymphoblastic leukemia (ALL) has extremely poor prognosis with median survival of less than 1 year. Donor lymphocyte infusion, second transplantation, chemotherapy or cytokine treatment have been tried as a salvage regimen without significant clinical benefit. Recently, blinatumomab, a bispecific monoclonal antibody targeting CD3-expressing T cells and CD19-expressing B-cell lineage malignant cells demonstrated promising outcomes in relapsed/refractory ALL patients...
July 2016: Immunotherapy
Jonathan E Benjamin, Anthony S Stein
Adults with relapsed/refractory B-acute lymphoblastic leukemia (ALL) have a complete remission (CR) rate of 20-45% and median overall survival of 3-9 months, depending on the duration of the first remission and number of lines of salvage therapy. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative option for adult patients with relapsed/refractory ALL, and achievement of CR is a crucial step before alloHSCT. Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct with dual specificity for CD19 and CD3, simultaneously binding CD3-positive cytotoxic T cells and CD19-positive B cells, resulting in T-cell-mediated serial lysis of normal and malignant B cells...
June 2016: Therapeutic Advances in Hematology
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