scholarly journals New drugs for acute myeloid leukemia inspired by genomics and when to use them

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Daniel A. Pollyea
Keyword(s):  
Acute Myeloid Leukemia ◽  
Targeted Therapies ◽  
Myeloid Leukemia ◽  
Clinical Care ◽  
Personalized Therapy ◽  
New Drugs ◽  
Targeted Sequencing ◽  
Minimal Toxicity ◽  
New Treatment ◽  
Acute Myeloid

Abstract We are several years into the “postdiscovery” era in acute myeloid leukemia (AML) thanks to extensive work involving the sequencing of genomes and exomes of countless patients, which has led to routine comprehensive targeted sequencing in clinical care. The ability to unlock the molecular underpinnings of each patient’s disease was supposed to usher in a new treatment era in which each patient was assigned, based on her mutational profile, a personalized cocktail of targeted therapies that would snuff the disease into submission with minimal toxicity. Whether we have fully realized the promise of personalized therapy in AML is unclear. Here, I review those new drugs that have been inspired by genomics, discuss others that might be possible and their potential roles, and consider whether the ability to target genomic mutations in a personalized manner constitutes the future of AML therapeutics or is representative of an era that has already passed.

scholarly journals How I treat acute myeloid leukemia in the era of new drugs

Blood ◽  
2020 ◽  
Vol 135 (2) ◽  
pp. 85-96 ◽  
Author(s):  
Courtney D. DiNardo ◽  
Andrew H. Wei
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
B Cell Lymphoma ◽  
New Drugs ◽  
Selective Treatment ◽  
Isocitrate Dehydrogenase 1 ◽  
Key Issues ◽  
New Treatment ◽  
Case Presentations ◽  
Acute Myeloid

Abstract The acute myeloid leukemia (AML) treatment landscape has changed substantially since 2017. New targeted drugs have emerged, including venetoclax to target B-cell lymphoma 2, midostaurin and gilteritinib to target FLT3, and ivosidenib and enasidenib to target mutant isocitrate dehydrogenase 1 and 2, respectively. Other additions include reapproval of gemtuzumab ozogomycin to target CD33, glasdegib to target the hedgehog pathway, and a liposomal formulation of daunorubicin and cytarabine (CPX-351). Genomically heterogeneous AML has a tendency to evolve, particularly under selective treatment pressure. For decades, treatment decisions have largely centered around chemotherapy drug intensity. Physicians now have access to an increasing number of drugs with novel mechanisms of action and distinctive side-effect profiles. Key issues faced by hematologists in this era of new drugs include (1) the timely identification of actionable mutations at diagnosis and at relapse; (2) deciding which drug to use among several therapeutic options; and (3) increasing awareness of how to anticipate, mitigate, and manage common complications associated with these new agents. This article will use 3 case presentations to discuss some of the new treatment challenges encountered in AML management, with the goal of providing practical guidance to aid the practicing physician.

Genomics of Acute Myeloid Leukemia Diagnosis and Pathways

2017 ◽  
Vol 35 (9) ◽  
pp. 934-946 ◽  
Author(s):  
Lars Bullinger ◽  
Konstanze Döhner ◽  
Hartmut Döhner
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Clinical Care ◽  
Clonal Expansion ◽  
Disease Classification ◽  
Disease Evolution ◽  
Myeloid Neoplasms ◽  
Increased Risk ◽  
Acute Myeloid

In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. The same genes are frequently found to be mutated in elderly individuals along with clonal expansion of hematopoiesis that confers an increased risk for the development of hematologic cancers. Furthermore, such mutations may persist after therapy, lead to clonal expansion during hematologic remission, and eventually lead to relapsed disease. In contrast, mutations involving NPM1 or signaling molecules (eg, FLT3, RAS) typically are secondary events that occur later during leukemogenesis. Genetic data are now being used to inform disease classification, risk stratification, and clinical care of patients. Two new provisional entities, AML with mutated RUNX1 and AML with BCR- ABL1, have been included in the current update of the WHO classification of myeloid neoplasms and AML, and mutations in three genes— RUNX1, ASXL1, and TP53—have been added in the risk stratification of the 2017 European LeukemiaNet recommendations for AML. Integrated evaluation of baseline genetics and assessment of minimal residual disease are expected to further improve risk stratification and selection of postremission therapy. Finally, the identification of disease alleles will guide the development and use of novel molecularly targeted therapies.

scholarly journals Target Therapy in Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Vasko Graklanov
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Acute Leukemia ◽  
Mechanism Of Action ◽  
Myeloid Leukemia ◽  
Target Therapy ◽  
New Drugs ◽  
Cytotoxic Treatment ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is the most common form of acute leukemia in elderly patients. Over the past four decades the basic therapeutic armamentarium was the standard cytotoxic treatment. The new insights in understanding the pathogenesis of AML was the momentum that revolutionized the treatment landscape in AML. The last five years unprecedented growth has been seen in the number of target therapy drugs for the treatment of AML. These new drugs did not just have a clinical benefit as single agents but also have improved AML patient outcomes if combined with conventional cytotoxic therapy. Here, we review recent advances in target-based therapy for patients with AML focusing on their mechanism of action and the results from already published clinical trials.

New drugs creating new challenges in acute myeloid leukemia

2019 ◽  
Vol 58 (12) ◽  
pp. 903-914 ◽  
Author(s):  
Ing S. Tiong ◽  
Andrew H. Wei
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
New Drugs ◽  
New Challenges ◽  
Acute Myeloid

scholarly journals Economic burden of elderly patients with acute myeloid leukemia treated in routine clinical care in the United States

2018 ◽  
Vol 71 ◽  
pp. 27-33 ◽  
Author(s):  
Jill A. Bell ◽  
Aaron Galaznik ◽  
Eileen Farrelly ◽  
Marlo Blazer ◽  
Sharanya Murty ◽  
...  
Keyword(s):  
United States ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Economic Burden ◽  
Myeloid Leukemia ◽  
Clinical Care ◽  
The United States ◽  
Routine Clinical Care ◽  
Acute Myeloid

scholarly journals From Bench to Bedside and Beyond: Therapeutic Scenario in Acute Myeloid Leukemia

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 357 ◽  
Author(s):  
Carmelo Gurnari ◽  
Maria Teresa Voso ◽  
Jaroslaw P. Maciejewski ◽  
Valeria Visconte
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Response To Therapy ◽  
New Drugs ◽  
Survival Outcomes ◽  
Variable Response ◽  
Therapeutic Approaches ◽  
Long Term Survivors ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a heterogeneous group of clonal disorders characterized by abnormal proliferation of undifferentiated myeloid progenitors, impaired hematopoiesis, and variable response to therapy. To date, only about 30% of adult patients with AML become long-term survivors and relapse and/or disease refractoriness are the major cause of treatment failure. Thus, this is an urgent unmet clinical need and new drugs are envisaged in order to ameliorate disease survival outcomes. Here, we review the latest therapeutic approaches (investigational and approved agents) for AML treatment. A specific focus will be given to molecularly targeted therapies for AML as a representation of possible agents for precision medicine. We will discuss experimental and preclinical data for FLT3, IDH1, BCL-2, Hedgehog pathway inhibitors, and epitherapy.

scholarly journals Low-intensity regimens versus standard-intensity induction strategies in acute myeloid leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062072091301 ◽  
Author(s):  
Norbert Vey
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Assessment Tools ◽  
New Drugs ◽  
Prognostic Scores ◽  
Hypomethylating Agents ◽  
Low Intensity ◽  
Acute Myeloid

Treatment options for elderly patients with acute myeloid leukemia (AML) remain limited. In this age group, AML is frequently associated with poor-risk features, while patients’ present comorbidities and reduced functional reserves. As such, intensive chemotherapy (ICT) is frequently too toxic or ineffective in elderly patients and is restricted to a select minority, though it is standard therapy for the youngest and fittest patients or for those belonging to either the favorable or intermediate-risk groups. The use of hypomethylating agents represent an effective alternative for patients who are unfit for ICT, yet the results remain unsatisfactory. In recent years, prognostic scores were developed that include geriatric assessment tools and improved risk-stratification. In addition, several effective new drugs have emerged. The combination of these drugs with hypomethylating agents or low-dose cytarabine has produced encouraging preliminary results that may change standard practices and offer an alternative to the dilemma of ICT versus low-intensity therapies.

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