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https://www.readbyqxmd.com/read/29741514/management-of-acute-lymphoblastic-leukemia-in-young-adults
#1
Lori S Muffly, Natalie Reizine, Wendy Stock
Substantial interest in acute lymphoblastic leukemia (ALL) in young adults (YAs) and investigations focused on this patient population have resulted in therapeutic advancements that are changing the management paradigm and improving outcomes. The pediatric ALL approach is feasible and effective when administered by medical oncologists. Advanced diagnostics and minimal residual disease measurements aid in prognostication and have resulted in shifting recommendations regarding allogeneic hematopoietic cell transplant in first remission...
February 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29713210/inotuzumab-ozogamicin-in-the-treatment-of-relapsed-refractory-acute-b-cell-lymphoblastic-leukemia
#2
REVIEW
Natalie Uy, Michelle Nadeau, Maximilian Stahl, Amer M Zeidan
The improvement in outcomes of adult patients with acute lymphoblastic leukemia (ALL) has been modest, with the exception of Philadelphia chromosome-positive disease, despite advances in supportive care and stem cell transplantation. The recent approvals of novel agents, including the bispecific T-cell engager blinatumomab, the antibody-drug conjugate inotuzumab ozogamicin, and chimeric antigen receptor T-cell products are changing the management of B-ALL, which traditionally relied on chemotherapy-based approaches...
2018: Journal of Blood Medicine
https://www.readbyqxmd.com/read/29572070/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-agents-targeting-lymphoid-or-myeloid-cells-surface-antigens-ii-cd22-cd30-cd33-cd38-cd40-slamf
#3
REVIEW
Lubos Drgona, Carlota Gudiol, Simone Lanini, Bernd Salzberger, Giuseppe Ippolito, Małgorzata Mikulska
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
March 20, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29544528/cd19-car-t-cell-therapy-for-relapsed-refractory-acute-lymphoblastic-leukemia-factors-affecting-toxicities-and-long-term-efficacies
#4
Li-Na Zhang, Yongping Song, Delong Liu
The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy...
March 15, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29517084/inotuzumab-ozogamicin-for-the-treatment-of-patients-with-acute-lymphocytic-leukemia
#5
A Choudhry, S M O'Brien
Inotuzumab ozogamicin is an antibody-drug conjugate comprised of a humanized anti-CD22 monoclonal antibody conjugated to calicheamicin, a cytotoxic antibiotic agent. Inotuzumab ozogamicin binds to CD22-expressing tumor cells, resulting in apoptotic cell death. Based on the results of the pivotal, phase III INO-VATE trial in acute lymphoblastic leukemia (ALL), approval of inotuzumab ozogamicin was recently granted for the treatment of patients with relapsed or refractory ALL, a group that otherwise has a poor prognosis with standard chemotherapy...
December 2017: Drugs of Today
https://www.readbyqxmd.com/read/29508899/patient-reported-outcomes-from-a-phase-3-randomized-controlled-trial-of-inotuzumab-ozogamicin-versus-standard-therapy-for-relapsed-refractory-acute-lymphoblastic-leukemia
#6
Hagop M Kantarjian, Yun Su, Elias J Jabbour, Helen Bhattacharyya, Eric Yan, Joseph C Cappelleri, David I Marks
BACKGROUND: Inotuzumab ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, demonstrated superior clinical activity versus standard-of-care (SOC) chemotherapies for relapsed/refractory B-cell acute lymphoblastic leukemia in the phase 3 randomized controlled INO-VATE trial. The authors assessed patient-reported outcomes (PROs) from that study. METHODS: Patients were randomized to receive either InO (1.8 mg/m2 per cycle for ≤6 cycles) or SOC (fludarabine/cytarabine [ara-C]/granulocyte colony-stimulating factor, or ara-C plus mitoxantrone, or high-dose ara-C for ≤4 cycles) and completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the EuroQoL 5 Dimensions Questionnaires at baseline, on day 1 of each cycle, and at the end of treatment...
May 15, 2018: Cancer
https://www.readbyqxmd.com/read/29423571/novel-therapies-for-older-adults-with-acute-lymphoblastic-leukemia
#7
REVIEW
Nicholas J Short, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi
PURPOSE OF REVIEW: Older adults with acute lymphoblastic leukemia (ALL) have worse survival compared to their younger counterparts. Here, we review the reasons for the poorer outcomes of older patients with ALL and also summarize the current and future therapeutic approaches to ALL in the elderly population. RECENT FINDINGS: The poor outcomes of older adults with ALL are driven largely by lack of tolerance to standard-dose chemotherapy, which leads to unacceptably high rates of myelosuppression-related deaths...
April 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29381191/efficacy-and-safety-analysis-by-age-cohort-of-inotuzumab-ozogamicin-in-patients-with-relapsed-or-refractory-acute-lymphoblastic-leukemia-enrolled-in-ino-vate
#8
Elias J Jabbour, Daniel J DeAngelo, Matthias Stelljes, Wendy Stock, Michaela Liedtke, Nicola Gökbuget, Susan O'Brien, Tao Wang, M Luisa Paccagnella, Barbara Sleight, Erik Vandendries, Anjali S Advani, Hagop M Kantarjian
BACKGROUND: Inotuzumab ozogamicin (InO) has demonstrated efficacy and tolerability in patients aged 18 to 78 years with relapsed/refractory acute lymphoblastic leukemia (ALL) in the INO-VATE trial. This subset analysis compared the efficacy and safety of InO in younger and older patients. METHODS: Intent-to-treat analyses of morphologic responses and overall survival (OS) included 326 randomized patients, and safety assessments included 307 patients receiving 1 or more doses of the study treatment...
April 15, 2018: Cancer
https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#9
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
February 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352702/inotuzumab-ozogamicin-in-older-patients-with-acute-lymphoblastic-leukaemia-premises-and-promises
#10
Carmelo Rizzari
No abstract text is available yet for this article.
February 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29330398/management-of-important-adverse-events-associated-with-inotuzumab-ozogamicin-expert-panel-review
#11
Partow Kebriaei, Corey Cutler, Marcos de Lima, Sergio Giralt, Stephanie J Lee, David Marks, Akil Merchant, Wendy Stock, Koen van Besien, Matthias Stelljes
No abstract text is available yet for this article.
April 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29300693/antibodies-to-watch-in-2018
#12
Hélène Kaplon, Janice M Reichert
The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016...
February 2018: MAbs
https://www.readbyqxmd.com/read/29296758/inotuzumab-ozogamicin-in-adults-with-relapsed-or-refractory-cd22-positive-acute-lymphoblastic-leukemia-a-phase-1-2-study
#13
Daniel J DeAngelo, Wendy Stock, Anthony S Stein, Andrei Shustov, Michaela Liedtke, Charles A Schiffer, Erik Vandendries, Katherine Liau, Revathi Ananthakrishnan, Joseph Boni, A Douglas Laird, Luke Fostvedt, Hagop M Kantarjian, Anjali S Advani
This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic leukemia. In phase 1, patients received InO 1.2 (n = 3), 1.6 (n = 12), or 1.8 (n = 9) mg/m2 per cycle on days 1, 8, and 15 over a 28-day cycle (≤6 cycles). The recommended phase 2 dose (RP2D) was confirmed (expansion cohort; n = 13); safety and activity of InO were assessed in patients receiving the RP2D in phase 2 (n = 35) and in all treated patients (n = 72)...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29239690/antibody-drug-conjugates-design-and-development-for-therapy-and-imaging-in-and-beyond-cancer-labex-mabimprove-industrial-workshop-july-27-28-2017-tours-france
#14
Camille Martin, Claire Kizlik-Masson, André Pèlegrin, Hervé Watier, Marie-Claude Viaud-Massuard, Nicolas Joubert
The annual "Antibody Industrial Symposium", co organized by LabEx MAbImprove, MabDesign and Polepharma, was held in Tours, France on June 27-28, 2017. The focus was on antibody-drug-conjugates (ADCs), new entities which realize the hope of Paul Ehrlich's magic bullet. ADCs result from the bioconjugation of a highly cytotoxic drug to a selective monoclonal antibody, which acts as a vector. Building on knowledge gained during the development of three approved ADCs, brentuximab vedotin (Adcetris®), ado trastuzumab emtansine (Kadcyla®) and inotuzumab ozogamicin (Besponsa®), and the many ADCs in development, this meeting addressed strategies and the latest innovations in the field from fundamental research to manufacturing...
February 2018: MAbs
https://www.readbyqxmd.com/read/29188435/antibody-drug-conjugates-pharmacokinetic-pharmacodynamic-modeling-preclinical-characterization-clinical-studies-and-lessons-learned
#15
REVIEW
William D Hedrich, Tamer E Fandy, Hossam M Ashour, Hongbing Wang, Hazem E Hassan
Antibody-drug conjugates are an emerging class of biopharmaceuticals changing the landscape of targeted chemotherapy. These conjugates combine the target specificity of monoclonal antibodies with the anti-cancer activity of small-molecule therapeutics. Several antibody-drug conjugates have received approval for the treatment of various types of cancer including gemtuzumab ozogamicin (Mylotarg® ), brentuximab vedotin (Adcetris® ), trastuzumab emtansine (Kadcyla® ), and inotuzumab ozogamicin, which recently received approval (Besponsa® )...
November 29, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29176353/new-developments-in-immunotherapy-for-pediatric-leukemia
#16
Jessica B Foster, Shannon L Maude
PURPOSE OF REVIEW: Immunotherapy for the treatment of cancer has advanced at a tremendous pace over the last decade. In this review, we provide an overview of recent progress in immunotherapy for the treatment of leukemia, focusing on antibody-drug conjugates (ADC), bi-specific T-cell engagers (BiTE), and chimeric antigen receptor (CAR) T cells. RECENT FINDINGS: Ongoing clinical trials of CAR T cells directed against CD19 have produced complete remission rates as high as 93%, prompting global multicenter phase 2 trials and the first FDA approval of a CAR T-cell therapy...
February 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29092647/inotuzumab-ozogamicin-for-the-treatment-of-acute-lymphoblastic-leukemia
#17
REVIEW
Ariella Tvito, Jacob M Rowe
Acute lymphoblastic leukemia (ALL) is an uncommon disorder that affects about 20% of adults with acute leukemia. Historically, those who relapse from this condition have a dismal prognosis. Recent developments in immunoconjugate usage has changed the landscape of lymphoid B-cell malignancy therapy. One recent development is the FDA approved therapy inotuzumab ozogamicin which has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to possibly increase the number of patients who may achieve a state of minimal residual disease...
December 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29050699/how-should-we-treat-a-patient-with-relapsed-ph-negative-b-all-and-what-novel-approaches-are-being-investigated
#18
REVIEW
Nicola Gökbuget
Despite significant improvements in outcome of newly diagnosed B-precursor ALL, the results in relapsed or refractory adult ALL are overall poor. Large retrospective studies revealed significant differences in terms of outcome, with particularly poor response rates in early or refractory relapses, whereas late relapses usually respond very well to repeated standard induction. Particularly new immunotherapy compounds like the CD19 bispecific antibody Blinatumomab and the conjugated CD22 antibody Inotuzumab yielded promising response rates compared to standard therapies in randomised trials...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050693/how-should-we-treat-older-adults-with-ph-adult-all-and-what-novel-approaches-are-being-investigated
#19
REVIEW
Matthew J Wieduwilt
Treatment of older patients with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia presents unique challenges. Advanced age, comorbidities, high treatment-related death rates with traditional chemotherapy, and relapse combine to yield poor survival. Reduced-intensity induction with BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) and corticosteroids yields CR rates 96-100% with no induction mortality but relapse is nearly certain without effective consolidation. Few clinical trials provide guidance on optimal consolidation for older Ph+ ALL...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29025266/the-abcs-of-immunotherapy-for-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#20
Troy Z Horvat, Amanda N Seddon, Adebayo Ogunniyi, Amber C King, Larry W Buie, Ryan J Daley
OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR)...
March 2018: Annals of Pharmacotherapy
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