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https://www.readbyqxmd.com/read/29296877/the-role-of-targeted-therapy-in-the-management-of-patients-with-aml
#1
REVIEW
Alexander E Perl
Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration's approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29283906/new-therapeutic-strategies-for-high-risk-acute-myeloid-leukemia
#2
Kamal Menghrajani, Martin S Tallman
PURPOSE OF REVIEW: Treatments for acute myeloid leukemia (AML) had remained essentially unchanged for several years; however, the advent of molecular testing has generated insight into the biology of this disease which is now being translated into clinical practice. New treatment strategies which improve drug delivery and exploit cellular targets are changing the landscape of how we treat this disease. RECENT FINDINGS: Induction therapy is in the process of changing for several patient populations...
December 27, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29240026/gemtuzumab-ozogamicin-containing-chemotherapy-for-relapsed-or-refractory-acute-myeloid-leukemia-aml-in-children
#3
Anthony Pak-Yin Liu, Alex Wing-Kwan Leung, Daniel Ka-Leung Cheuk, Vincent Lee, Shau-Yin Ha
No abstract text is available yet for this article.
December 12, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29222237/the-role-of-targeted-therapy-in-the-management-of-patients-with-aml
#4
REVIEW
Alexander E Perl
Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration's approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29206680/immune-therapies-in-acute-myeloid-leukemia-a-focus-on-monoclonal-antibodies-and-immune-checkpoint-inhibitors
#5
Rita Assi, Hagop Kantarjian, Farhad Ravandi, Naval Daver
PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML...
December 4, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29188435/antibody-drug-conjugates-pharmacokinetic-pharmacodynamic-modeling-preclinical-characterization-clinical-studies-and-lessons-learned
#6
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
#7
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/29172076/gemtuzumab-ozogamicin-go-inclusion-to-induction-chemotherapy-eliminates-leukemic-initiating-cells-and-significantly-improves-survival-in-mouse-models-of-acute-myeloid-leukemia
#8
Cathy C Zhang, Zhengming Yan, Bernadette Pascual, Amy Jackson-Fisher, Donghui Stephen Huang, Qing Zong, Mark Elliott, Conglin Fan, Nanni Huser, Joseph Lee, Matthew Sung, Puja Sapra
Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML). Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs)...
November 21, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29156201/which-new-agents-will-be-incorporated-into-frontline-therapy-in-acute-myeloid-leukemia
#9
REVIEW
Richard M Stone
For 4 decades, new agents had not been permanently approved for use in treating acute myeloid leukemia (AML). The long dry spell was broken in 2017, however, with the approval of several agents: midostaurin for addition to chemotherapy in mutant FLT3 patients undergoing intensive chemotherapy, enasidenib in advanced mutant IDH2 patients, CPX-351 in secondary AML patients, and gemtuzumab ozogamicin in conjunction with standard chemotherapy in AML. This review surveys the use of tyrosine kinase inhibitors to treat patients with mutant FLT3 AML, mutant KIT AML, as well as IDH inhibitors and explores some questions regarding their integration into the treatment armamentarium for AML...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156199/how-can-one-optimize-induction-therapy-in-aml
#10
REVIEW
Selina M Luger
Induction therapy for acute myeloid leukemia has not changed much since 1973, when the 7 + 3 regimen of cytarabine and daunorubicin was born. Since then, various strategies have been evaluated to improve patient response, including dose intensification, the incorporation of additional agents into the regimen, the development of novel agents, and modified approaches for older patients. Recently, two novel agents, CPX-351 and gemtuzumab ozogamicin, have been approved by the US Food and Drug Administration. This review discusses each of the induction strategies and their impact on patient outcomes...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29071049/clinical-and-experimental-efficacy-of-gemtuzumab-ozogamicin-in-core-binding-factor-acute-myeloid-leukemia
#11
Michele Gottardi, Federico Mosna, Sergio de Angeli, Cristina Papayannidis, Anna Candoni, Marino Clavio, Cristina Tecchio, Andrea Piccin, Marta Campo dell'Orto, Fabio Benedetti, Giovanni Martinelli, Filippo Gherlinzoni
No abstract text is available yet for this article.
September 26, 2017: Hematology Reports
https://www.readbyqxmd.com/read/29051180/midostaurin-enasidenib-cpx-351-gemtuzumab-ozogamicin-and-venetoclax-bring-new-hope-to-aml
#12
REVIEW
Andrew H Wei, Ing S Tiong
In 2017, 4 drugs received US Food and Drug Administration marketing approval for acute myeloid leukemia (AML) treatment: targeted therapies for mutant FLT3 and IDH2, a liposomal cytarabine-daunorubicin formulation for therapy-related AML and AML with myelodysplasia-related changes, and resurgence of an antibody-drug conjugate designed to target CD33. Promising results also emerged for the BCL-2 inhibitor venetoclax combined with low-intensity therapy in older patients unfit for intensive chemotherapy. This quintet of new drugs is likely to reshape the therapeutic landscape of AML...
December 7, 2017: Blood
https://www.readbyqxmd.com/read/29021230/gemtuzumab-ozogamicin-for-acute-myeloid-leukemia
#13
Frederick R Appelbaum, Irwin D Bernstein
On 1 September 2017, the US Food and Drug Administration (FDA) approved gemtuzumab ozogamicin (GO) for the treatment of adults with newly diagnosed CD33+ acute myeloid leukemia and for patients aged ≥2 years with CD33+ acute myeloid leukemia who have experienced a relapse or who have not responded to initial treatment. This signals a new chapter in the long and unusual story of GO, which was the first antibody-drug conjugate approved for human use by the FDA.
November 30, 2017: Blood
https://www.readbyqxmd.com/read/28931515/gemtuzumab-ozogamicin-makes-a-comeback
#14
(no author information available yet)
After being pulled from the market 7 years ago, gemtuzumab ozogamicin has been reapproved by the FDA, this time for adults newly diagnosed with acute myeloid leukemia, as well as patients 2 years of age and older with relapsed/refractory disease. The CD33-targeting antibody-drug conjugate can be given as a single agent or in combination with chemotherapy.
September 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28857842/relapsed-refractory-acute-myeloid-leukemia-any-progress
#15
Richard F Schlenk, Carsten Müller-Tidow, Axel Benner, Meinhard Kieser
PURPOSE OF REVIEW: Aim of this review was to focus on prognostic and predictive factors, standard and new treatment approaches, and on statistical considerations for future clinical trials in patients with relapsed/refractory acute myeloid leukemia (r/r-AML). RECENT FINDINGS: New prognostic molecular markers were identified in r/r-AML, FLT3-ITD, mutated IDH1, and biallelic CEBPA mutations. Intensive combination chemotherapy including gemtuzumab ozogamicin emerged as an effective salvage therapy in refractory AML...
November 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28804680/treatment-of-older-patients-with-acute-myeloid-leukemia-aml-revised-canadian-consensus-guidelines
#16
REVIEW
Joseph M Brandwein, Nancy Zhu, Rajat Kumar, Brian Leber, Mitchell Sabloff, Irwindeep Sandhu, Jeannine Kassis, Harold J Olney, Mohamed Elemary, Andre C Schuh
The treatment of acute myeloid leukemia (AML) in older patients is undergoing rapid changes, with a number of important publications in the past five years. Because of this, a group of Canadian leukemia experts has produced an update to the Canadian Consensus Guidelines that were published in 2013, with several new agents recommended, subject to availability. Recent studies have supported the survival benefit of induction chemotherapy for patients under age 80, except those with major co-morbidities or those with adverse risk cytogenetics who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT)...
2017: American Journal of Blood Research
https://www.readbyqxmd.com/read/28674028/gemtuzumab-ozogamicin-in-infants-with-aml-results-from-the-children-s-oncology-group-trials-aaml03p1-and-aaml0531
#17
LETTER
Erin M Guest, Richard Aplenc, Lillian Sung, Susana C Raimondi, Betsy A Hirsch, Todd A Alonzo, Robert B Gerbing, Yi-Cheng Jim Wang, Samir B Kahwash, Amy Heerema-McKenney, Soheil Meshinchi, Alan S Gamis
No abstract text is available yet for this article.
August 17, 2017: Blood
https://www.readbyqxmd.com/read/28644774/cd33-splicing-polymorphism-determines-gemtuzumab-ozogamicin-response-in-de-novo-acute-myeloid-leukemia-report-from-randomized-phase-iii-children-s-oncology-group-trial-aaml0531
#18
RANDOMIZED CONTROLLED TRIAL
Jatinder K Lamba, Lata Chauhan, Miyoung Shin, Michael R Loken, Jessica A Pollard, Yi-Cheng Wang, Rhonda E Ries, Richard Aplenc, Betsy A Hirsch, Susana C Raimondi, Roland B Walter, Irwin D Bernstein, Alan S Gamis, Todd A Alonzo, Soheil Meshinchi
Purpose Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C>T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy...
August 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28607471/gemtuzumab-ozogamicin-in-acute-myeloid-leukemia
#19
REVIEW
C D Godwin, R P Gale, R B Walter
CD33 is variably expressed on leukemia blasts in almost all patients with acute myeloid leukemia (AML) and possibly leukemia stem cells in some. Efforts to target CD33 therapeutically have focused on gemtuzumab ozogamicin (GO; Mylotarg), an antibody-drug conjugate delivering a DNA-damaging calicheamicin derivative. GO is most effective in acute promyelocytic leukemia but induces remissions in other AML types and received accelerated approval in the US in 2000. However, because a large follow-up study showed no survival improvement and increased early deaths the drug manufacturer voluntarily withdrew the US New Drug Application in 2010...
September 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28494506/minimal-residual-disease-eradication-with-epigenetic-therapy-in-core-binding-factor-acute-myeloid-leukemia
#20
Brittany Knick Ragon, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M Kantarjian, Gautam Borthakur
Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival...
September 2017: American Journal of Hematology
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