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Blinatumomab

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https://www.readbyqxmd.com/read/28494518/correlates-of-resistance-and-relapse-during-blinatumomab-therapy-for-relapsed-refractory-acute-lymphoblastic-leukemia
#1
Ibrahim Aldoss, Joo Song, Tracey Stiller, Tina Nguyen, Joycelynne Palmer, Margaret O'Donnell, Anthony S Stein, Guido Marcucci, Stephen Forman, Vinod Pullarkat
We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM-ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts >50%) (P=0.02), history of prior EM-ALL (P=0...
May 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28469973/the-development-of-bispecific-antibodies-and-their-applications-in-tumor-immune-escape
#2
REVIEW
Xiaolong Zhang, Yuanyuan Yang, Dongmei Fan, Dongsheng Xiong
During the past two decades, a great evolution of bispecific antibodies (BsAbs) for therapeutic applications has been made. BsAbs can bind simultaneously two different antigens or epitopes, which leads to a wide range of applications including redirecting T cells or NK cells to tumor cells, blocking two different signaling pathways, dual targeting of different disease mediators, and delivering payloads to targeted sites. Aside from approved catumaxomab (anti-CD3 and anti-EpCAM) and blinatumomab (anti-CD3 and anti-CD19), many more BsAbs are now in various phases of clinical development...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28453885/lineage-switch-under-blinatumomab-treatment-of-relapsed-common-acute-lymphoblastic-leukemia-without-mll-rearrangement
#3
Annabelle Zoghbi, Udo Zur Stadt, Beate Winkler, Ingo Müller, Gabriele Escherich
Blinatumomab is a bispecific T-cell engaging αCD19 antibody used in refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL). Recently, lineage switch to a myeloid phenotype has been described following CD19 targeting treatment in three pediatric patients with mixed lineage leukemia (MLL) rearranged ALL. We report the case of a female who received blinatumomab for a first relapse of ALL without MLL alterations. She suffered from a second relapse early after hematopoietic stem cell transplantation and was treated with blinatumomab again...
April 28, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28389575/blinatumomab-has-activity-in-patients-with-tki-refractory-ph-all
#4
(no author information available yet)
Blinatumomab achieved complete remission with full or partial hematologic recovery in 36% of patients.
April 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28379283/blinatumomab-blincyto%C3%A2-lessons-learned-from-the-bispecific-t-cell-engager-bite%C3%A2-in-acute-lymphocytic-leukemia-all
#5
Greg Friberg, David Reese
BiTE® antibody constructs are single-chain bispecific antibodies with specificity for CD3 on the T cell and a selected surface antigen on a tumor cell. When infused into patients, they are capable of eliciting a polyclonal T cell response that is unrestricted by T cell receptor specificity, presence of MHC class, or additional T cell co-stimuli. The most clinically advanced is the CD19/CD3 construct blinatumomab (Blincyto®), which is approved in the US and EU for relapsed and refractory Philadelphia negative B-cell precursor ALL...
March 31, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28355115/complete-hematologic-and-molecular-response-in-adult-patients-with-relapsed-refractory-philadelphia-chromosome-positive-b-precursor-acute-lymphoblastic-leukemia-following-treatment-with-blinatumomab-results-from-a-phase-ii-single-arm-multicenter-study
#6
Giovanni Martinelli, Nicolas Boissel, Patrice Chevallier, Oliver Ottmann, Nicola Gökbuget, Max S Topp, Adele K Fielding, Alessandro Rambaldi, Ellen K Ritchie, Cristina Papayannidis, Lulu Ren Sterling, Jonathan Benjamin, Anthony Stein
Purpose Few therapeutic options are available for patients with Philadelphia chromosome-positive (Ph(+)) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) -based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph(+) ALL. Patients and Methods This open-label phase II study enrolled adults with Ph(+) ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib...
March 29, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28303311/-immunotherapy-of-cancer-with-checkpoint-inhibitors-not-only-in-malignant-melanoma
#7
A Neubauer
The newest weapon in cancer therapy is checkpoint inhibition, which is the result of basic immunology research. The success of this therapy is based on the fact that upon light microscopy, many solid tumors harbor lymphocytic cells infiltrating the tumor (TILs), and in many solid tumors, the presence of these TILs are prognostic. Ipilimumab was the first monoclonal antibody developed against a target present on T cells after becoming activated, CTLA-4. In malignant melanoma, ipilimumab showed its beneficial effect as compared to a placebo peptide...
March 16, 2017: Der Internist
https://www.readbyqxmd.com/read/28290492/haematological-cancer-treg-predict-responsiveness-to-blinatumomab
#8
Peter Sidaway
No abstract text is available yet for this article.
May 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28285842/blinatumomab-significantly-improves-overall-survival
#9
Talha Khan Burki
No abstract text is available yet for this article.
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28273193/-drug-therapy-of-lymphomas
#10
Lajos Gergely
The therapy of lymphomas has undergone a major expansion during the last decade. Novel therapeutic targets have appeared beyond classical chemotherapeutic combinations. These novel drugs have very pronounced action across lymphoma types, and their toxicity profile is usually better tolerable compared to standard chemotherapies. These new therapies are enabling us to offer treatment to those patients who have refractory disease, and we had no option to treat them before these drugs. The author describes several new therapeutic options...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28249141/blinatumomab-versus-chemotherapy-for-advanced-acute-lymphoblastic-leukemia
#11
RANDOMIZED CONTROLLED TRIAL
Hagop Kantarjian, Anthony Stein, Nicola Gökbuget, Adele K Fielding, Andre C Schuh, Josep-Maria Ribera, Andrew Wei, Hervé Dombret, Robin Foà, Renato Bassan, Önder Arslan, Miguel A Sanz, Julie Bergeron, Fatih Demirkan, Ewa Lech-Maranda, Alessandro Rambaldi, Xavier Thomas, Heinz-August Horst, Monika Brüggemann, Wolfram Klapper, Brent L Wood, Alex Fleishman, Dirk Nagorsen, Christopher Holland, Zachary Zimmerman, Max S Topp
BACKGROUND: Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. METHODS: In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard-of-care chemotherapy...
March 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28243848/new-treatment-strategies-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#12
REVIEW
Lalit Saini, Joseph Brandwein
PURPOSE OF REVIEW: To review recent studies that address important questions regarding the treatment of Philadelphia chromosome-positive ALL. RECENT FINDINGS: Less intensive non-myelosuppressive induction approaches can produce comparable anti-leukemic responses with less toxicity. Second-generation tyrosine kinase inhibitors (TKIs) are not clearly associated with superior outcomes compared to imatinib. Ponatinib is associated with lower early relapse rates, but has additional vascular risks...
April 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28228105/mesenchymal-stromal-cells-as-vehicles-of-tetravalent-bispecific-tandab-cd3-cd19-for-the-treatment-of-b-cell-lymphoma-combined-with-ido-pathway-inhibitor-d-1-methyl-tryptophan
#13
Xiaolong Zhang, Yuanyuan Yang, Leisheng Zhang, Yang Lu, Qing Zhang, Dongmei Fan, Yizhi Zhang, Yanjun Zhang, Zhou Ye, Dongsheng Xiong
BACKGROUND: Although blinatumomab, a bispecific T cell engaging antibody, exhibits high clinical response rates in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations because of its short half-life. Mesenchymal stromal cells (MSCs) represent an attractive approach for delivery of therapeutic agents to cancer sites owing to their tropism towards tumors, but their immunosuppression capabilities, especially induced by indoleamine 2,3-dioxygenase (IDO), should also be taken into consideration...
February 23, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28205134/minimal-residual-disease-in-acute-lymphoblastic-leukemia-how-to-recognize-and-treat-it
#14
REVIEW
Nicholas J Short, Elias Jabbour
In recent years, the identification of minimal residual disease (MRD) that persists after chemotherapy has emerged as the most powerful tool in determining the prognosis of patients with ALL, often superseding historically relevant prognostic factors. Multiple methods to detect MRD exist, each with their own advantages and disadvantages. Multiparameter flow cytometry and quantitative polymerase chain reaction are the most commonly used methods of MRD detection in clinical practice, although there is promise in the use of more sensitive assays utilizing next-generation sequencing that may be able to further refine MRD-based risk stratification...
January 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28182247/translation-and-clinical-development-of-bispecific-t-cell-engaging-antibodies-for-cancer-treatment
#15
REVIEW
T Yuraszeck, S Kasichayanula, J E Benjamin
Bispecific T-cell Engagers (BiTE®) antibody constructs enable a polyclonal T-cell response to cell-surface tumor-associated antigens, bypassing the narrow specificities of T-cell receptors and the need for antigen presentation through the major histocompatibility complex pathways. Blinatumomab, a CD19xCD3 BiTE® antibody construct, received accelerated approval for the treatment of relapsed/refractory Philadelphia chromosome negative acute lymphoblastic leukemia. Herein we review the pharmacology, safety, and efficacy observed in studies of blinatumomab and other BiTE® antibody constructs...
May 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28119525/frequency-of-regulatory-t-cells-determines-the-outcome-of-the-t-cell-engaging-antibody-blinatumomab-in-patients-with-b-precursor-all
#16
J Duell, M Dittrich, T Bedke, T Mueller, F Eisele, A Rosenwald, L Rasche, E Hartmann, T Dandekar, H Einsele, M S Topp
Blinatumomab can induce a complete haematological remission in patients in 46.6% with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) resulting in a survival benefit when compared with chemotherapy. Only bone marrow blast counts before therapy have shown a weak prediction of response. Here we investigated the role of regulatory T cells (Tregs), measured by CD4/CD25/FOXP3 expression, in predicting the outcome of immunotherapy with the CD19-directed bispecific T-cell engager construct blinatumomab...
February 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096698/burkitt-lymphoma-in-adolescents-and-young-adults-management-challenges
#17
REVIEW
Massimo Dozzo, Francesca Carobolante, Pietro Maria Donisi, Annamaria Scattolin, Elena Maino, Rosaria Sancetta, Piera Viero, Renato Bassan
About one-half of all Burkitt lymphoma (BL) patients are younger than 40 years, and one-third belong to the adolescent and young adult (AYA) subset, defined by an age between 15 and 25-40 years, based on selection criteria used in different reports. BL is an aggressive B-cell neoplasm displaying highly characteristic clinico-diagnostic features, the biologic hallmark of which is a translocation involving immunoglobulin and c-MYC genes. It presents as sporadic, endemic, or epidemic disease. Endemicity is pathogenetically linked to an imbalance of the immune system which occurs in African children infected by malaria parasites and Epstein-Barr virus, while the epidemic form strictly follows the pattern of infection by HIV...
2017: Adolescent Health, Medicine and Therapeutics
https://www.readbyqxmd.com/read/28088906/epratuzumab-and-blinatumomab-as-therapeutic-antibodies-for-treatment-of-pediatric-acute-lymphoblastic-leukemia-current-status-and-future-perspectives
#18
Raffaella Franca, Diego Favretto, Marilena Granzotto, Giuliana Decorti, Marco Rabusin, Gabriele Stocco
BACKGROUND: More than 85% of children affected by acute lymphoblastic leukemia (ALL) are successfully treated; however relapse remains a remarkable clinical concern, with 50-60% of relapsing patients facing a fatal outcome. Management of relapsed patients includes standardized intensive risk-adapted regimens based on conventional drugs, and hematopoietic stem cells transplantation for patients with unfavourable features. Biological drugs, in particular the monoclonal antibody epratuzumab and the bi-functional recombinant single chain peptide blinatumomab, have been recently recognized as novel potential agents to be integrated in salvage ALL therapy to further improve rescue outcome...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28028314/redirecting-t-cells-to-eradicate-b-cell-acute-lymphoblastic-leukemia-bispecific-t-cell-engagers-and-chimeric-antigen-receptors
#19
REVIEW
I Aldoss, R C Bargou, D Nagorsen, G R Friberg, P A Baeuerle, S J Forman
Recent advances in antibody technology to harness T cells for cancer immunotherapy, particularly in the difficult-to-treat setting of relapsed/refractory acute lymphoblastic leukemia (r/r ALL), have led to innovative methods for directing cytotoxic T cells to specific surface antigens on cancer cells. One approach involves administration of soluble bispecific (or dual-affinity) antibody-based constructs that temporarily bridge T cells and cancer cells. Another approach infuses ex vivo-engineered T cells that express a surface plasma membrane-inserted antibody construct called a chimeric antigen receptor (CAR)...
April 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27998223/phase-i-phase-ii-study-of-blinatumomab-in-pediatric-patients-with-relapsed-refractory-acute-lymphoblastic-leukemia
#20
Arend von Stackelberg, Franco Locatelli, Gerhard Zugmaier, Rupert Handgretinger, Tanya M Trippett, Carmelo Rizzari, Peter Bader, Maureen M O'Brien, Benoît Brethon, Deepa Bhojwani, Paul Gerhardt Schlegel, Arndt Borkhardt, Susan R Rheingold, Todd Michael Cooper, Christian M Zwaan, Phillip Barnette, Chiara Messina, Gérard Michel, Steven G DuBois, Kuolung Hu, Min Zhu, James A Whitlock, Lia Gore
Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II)...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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