Novel Approaches to the Treatment of Acute Myeloid Leukemia

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Gail J. Roboz
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Molecular Genetic ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
The United States ◽  
Current Treatment ◽  
Treatment Standards ◽  
Acute Myeloid

Abstract Approximately 12 000 adults are diagnosed with acute myeloid leukemia (AML) in the United States annually, the majority of whom die from their disease. The mainstay of initial treatment, cytosine arabinoside (ara-C) combined with an anthracycline, was developed nearly 40 years ago and remains the worldwide standard of care. Advances in genomics technologies have identified AML as a genetically heterogeneous disease, and many patients can now be categorized into clinicopathologic subgroups on the basis of their underlying molecular genetic defects. It is hoped that enhanced specificity of diagnostic classification will result in more effective application of targeted agents and the ability to create individualized treatment strategies. This review describes the current treatment standards for induction, consolidation, and stem cell transplantation; special considerations in the management of older AML patients; novel agents; emerging data on the detection and management of minimal residual disease (MRD); and strategies to improve the design and implementation of AML clinical trials.

scholarly journals Clonal hematopoiesis and measurable residual disease assessment in acute myeloid leukemia

Blood ◽  
2020 ◽  
Vol 135 (20) ◽  
pp. 1729-1738 ◽  
Author(s):  
Robert P. Hasserjian ◽  
David P. Steensma ◽  
Timothy A. Graubert ◽  
Benjamin L. Ebert
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Molecular Genetic ◽  
Disease Assessment ◽  
Clonal Hematopoiesis ◽  
Myeloid Neoplasm ◽  
Measurable Residual Disease ◽  
Acute Myeloid

Abstract Current objectives regarding treatment of acute myeloid leukemia (AML) include achieving complete remission (CR) by clinicopathological criteria followed by interrogation for the presence of minimal/measurable residual disease (MRD) by molecular genetic and/or flow cytometric techniques. Although advances in molecular genetic technologies have enabled highly sensitive detection of AML-associated mutations and translocations, determination of MRD is complicated by the fact that many treated patients have persistent clonal hematopoiesis (CH) that may not reflect residual AML. CH detected in AML patients in CR includes true residual or early recurrent AML, myelodysplastic syndrome or CH that is ancestral to the AML, and independent or newly emerging clones of uncertain leukemogenic potential. Although the presence of AML-related mutations has been shown to be a harbinger of relapse in multiple studies, the significance of other types of CH is less well understood. In patients who undergo allogeneic hematopoietic cell transplantation (HCT), post-HCT clones can be donor-derived and in some cases engender a new myeloid neoplasm that is clonally unrelated to the recipient’s original AML. In this article, we discuss the spectrum of CH that can be detected in treated AML patients, propose terminology to standardize nomenclature in this setting, and review clinical data and areas of uncertainty among the various types of posttreatment hematopoietic clones.

Genetic and immunophenotypical diagnostics for acute myeloid leukemia and their implication on treatment strategy

2012 ◽  
Vol 0 (0) ◽  
pp. -
Author(s):  
Sabine Kayser ◽  
Richard F. Schlenk
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Strategy ◽  
Myeloid Leukemia ◽  
Molecular Genetic ◽  
Treatment Strategies ◽  
Disease Classification ◽  
Novel Drugs ◽  
Genetic Abnormalities ◽  
Binding Factor ◽  
Acute Myeloid

AbstractCytogenetic and molecular genetic abnormalities in acute myeloid leukemia (AML) play an important role in the pathogenesis, are absolutely necessary for disease classification, are the most important prognostic factors for induction success and survival, and are increasingly used for specific genotype-adapted treatment approaches. In particular, molecular-targeted treatment strategies are evolving within clinical trials in the AML entities core-binding factor AML, characterized by t(8;21) and inv(16)/t(16;16), and AML with mutated NPM1, as well as AML with an internal tandem duplication of the FMS-related tyrosine kinase 3 (FLT3) gene. The link between the leukemogenic importance of genetic abnormalities and their role as a potential target for well-known and novel drugs will contribute to the stepwise replacement of purely risk-adapted therapy to a more and more genotype-adapted treatment strategy.

scholarly journals Cytotoxic therapy in acute myeloid leukemia: not quite dead yet

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 51-62 ◽  
Author(s):  
Laura C. Michaelis
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Disease Risk ◽  
Standard Of Care ◽  
Current Treatment ◽  
Lymphocytic Leukemia ◽  
Treatment Expectations ◽  
New Agents ◽  
Clinical Tools ◽  
Acute Myeloid

AbstractGiven the recent approvals of new agents for acute myeloid leukemia (AML), a clinical trial pipeline stocked with novel therapies, and the rapid integration of imaginative approaches in diseases like acute lymphocytic leukemia and chronic lymphocytic leukemia, it is reasonable to ask whether treatment of AML might finally depart from the classical cytotoxic induction therapy that has been employed since the 1970s. However, for better or worse, in 2018, cytotoxic induction regimens remain the standard of care for most patients. Indeed, the future likely lies in combinations of therapies that act with a spectrum of mechanisms. Using a case-based format, this review will outline current treatment expectations for patients according to karyotypic risk and familiarize readers with the basis for common induction choices. Relapsed/refractory disease may be especially amenable to interventions with novel agents or clinical trials; however, there are still some patients who most benefit from intensive chemotherapy. This review will outline risk systems that help the practitioner identify those with the best chances for response and survival. Finally, clinical tools, including geriatric assessments and comorbidity calculators, may help clinicians recognize patients for whom disease risk and comorbidity tip the balance against classical chemotherapy, a frequent challenge for those who treat this devastating disease.

scholarly journals Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5722
Author(s):  
Maximilian Fleischmann ◽  
Ulf Schnetzke ◽  
Andreas Hochhaus ◽  
Sebastian Scholl
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Current Status ◽  
Epigenetic Therapy ◽  
Comprehensive Overview ◽  
Secondary Resistance ◽  
Acute Myeloid

Treatment of acute myeloid leukemia (AML) has improved in recent years and several new therapeutic options have been approved. Most of them include mutation-specific approaches (e.g., gilteritinib for AML patients with activating FLT3 mutations), or are restricted to such defined AML subgroups, such as AML-MRC (AML with myeloid-related changes) or therapy-related AML (CPX-351). With this review, we aim to present a comprehensive overview of current AML therapy according to the evolved spectrum of recently approved treatment strategies. We address several aspects of combined epigenetic therapy with the BCL-2 inhibitor venetoclax and provide insight into mechanisms of resistance towards venetoclax-based regimens, and how primary or secondary resistance might be circumvented. Furthermore, a detailed overview on the current status of AML immunotherapy, describing promising concepts, is provided. This review focuses on clinically important aspects of current and future concepts of AML treatment, but will also present the molecular background of distinct targeted therapies, to understand the development and challenges of clinical trials ongoing in AML patients.

scholarly journals The Current Understanding of and Treatment Paradigm for Newly-Diagnosed TP53-Mutated Acute Myeloid Leukemia

Hemato ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 748-763
Author(s):  
Rory M. Shallis ◽  
Maximilian Stahl ◽  
Jan Philipp Bewersdorf ◽  
Amer M. Zeidan
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Disease Status ◽  
Current Treatment ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Treatment Paradigm ◽  
The Impact ◽  
Acute Myeloid

About 10% of newly diagnosed and 20–30% of therapy-related acute myeloid leukemia (AML) harbors a TP53 mutation (mTP53-AML). Unfortunately, this biological subset predicts one of the worst prognoses among patients with AML, specifically a median overall survival of about 7 months with fewer than 10% of patients eventually cured of disease. Although remission rates appear to be increased with venetoclax-based, less-intensive regimens when compared with contemporary, intensive chemotherapy (55–65% vs. 40%), survival appears to be no different between the two approaches. Attempts to discern whether or not the prognosis of mTP53-AML is universally poor have centered around the study of concurrent cytogenetic risk and predicted TP53 allelic state, measurable residual disease status and the impact of conditioning intensity for patients proceeding to allogeneic hematopoietic stem cell transplantation. We discuss these considerations in this review and offer the current treatment approach to TP53-mutated AML.

scholarly journals Clinical Applications of MicroRNAs in Acute Myeloid Leukemia: A Mini-Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Bhavana Bhatnagar ◽  
Ramiro Garzon
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Clinical Applications ◽  
Response To Therapy ◽  
Medical Decision ◽  
Cellular Processes ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid

MicroRNAs (miRs) are short non-coding RNAs, typically 18-25 nucleotides in length, that are critically important, through their direct effects on target mRNAs, in a variety of cellular processes including cell differentiation, proliferation and survival. Dysregulated miR expression has been identified in numerous cancer types including acute myeloid leukemia (AML). From a clinical standpoint, several miRs have been shown to associate with prognosis in AML patients. Furthermore, they also carry the potential to be used as biomarkers and to inform medical decision making. In addition, several preclinical studies have provided strong rationale to develop novel therapeutic strategies to target miRs in AML. This review will focus on potential clinical applications of miRs in adult AML and will discuss unique miR signatures in specific AML subtypes, their role in prognostication and response to therapy, as well as miRs that are promising therapeutic targets and ongoing clinical trials directed towards targeting clinically relevant miRs in AML that could allow for improvements in current treatment strategies.

scholarly journals Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape

2017 ◽  
Vol 8 (6) ◽  
pp. 185-195 ◽  
Author(s):  
Valeriy Sedov ◽  
Robert K. Stuart
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Standard Of Care ◽  
Initial Response ◽  
Current Treatment ◽  
Phase Iii ◽  
Double Blind ◽  
Poor Outcomes ◽  
Acute Myeloid

Treatment for acute myeloid leukemia (AML) generally consists of a combination of cytarabine and an anthracycline. Although induction therapy leads to complete remission (CR) for most patients, refractoriness to chemotherapy or relapse after initial response is associated with poor outcomes. The 1-year survival rates after first relapse have been reported at 29%, declining to 11% at 5 years. Prognosis is particularly poor among older patients whose higher prevalence of unfavorable cytogenetics and high frequency of comorbidities diminish their ability to tolerate intensive chemotherapy. There is no standard of care for relapsed/refractory (R/R) AML, and no new therapies have shown consistently superior outcomes in this setting in over two decades. Vosaroxin is an anticancer quinolone derivative (AQD) that was evaluated in combination with cytarabine for the treatment of R/R AML in the randomized, double-blind, placebo-controlled, phase III VALOR study ( n = 711). Compared with placebo/cytarabine, the vosaroxin/cytarabine regimen demonstrated favorable CR rates and survival in patients ⩾60 years of age, with toxicities similar to other AML regimens. Here we review outcomes of recent studies of commonly used chemotherapy regimens for the treatment of R/R AML and evaluate the results of the VALOR trial in the context of the current treatment landscape.

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