More Versus Less Therapy for Older Adults With Acute Myeloid Leukemia: New Perspectives on an Old Debate

Author(s):  
Heidi D. Klepin ◽  
Elihu Estey ◽  
Tapan Kadia

Most patients with newly diagnosed acute myeloid leukemia (AML) are at least age 65 and continue to have short survival, with many patients receiving no specific anti-AML therapy, particularly if they are older than age 75. Although consensus regarding optimal treatment of this growing population is lacking, treatment options are expanding even for the oldest patients. A fundamental question when seeing an older patient with AML is whether to recommend “more intensive” or “less intensive” induction therapy. Existing data can support more intensive treatment strategies for selected older adults, although there is growing evidence to support less intensive therapies as well. Randomized trials to provide clear comparisons between treatment strategies among well-characterized older adult populations are lacking. Reliance on age alone to determine treatment choice is problematic, as “fitness” or “unfitness” varies dramatically among patients of the same chronologic age and remains poorly characterized in existing studies. This article will provide differing perspectives on the “more” versus “less” question, with particular attention to recent drug approvals. Issues relevant to both treatment decision-making in practice and alternative trial design to inform gaps in knowledge will be discussed. Given the heterogeneity, an important conclusion will be that there is unlikely to be a single best approach and that appropriate decision-making requires considerations of many factors specific to individual patients.

2015 ◽  
Vol 15 (8) ◽  
pp. 477-483 ◽  
Author(s):  
Jihane Fattoum ◽  
Giovanna Cannas ◽  
Mohamed Elhamri ◽  
Isabelle Tigaud ◽  
Adriana Plesa ◽  
...  

2016 ◽  
Vol 26 (12) ◽  
pp. 2063-2068 ◽  
Author(s):  
Thomas W. LeBlanc ◽  
Laura J. Fish ◽  
Catherine T. Bloom ◽  
Areej El-Jawahri ◽  
Debra M. Davis ◽  
...  

2014 ◽  
Vol 32 (24) ◽  
pp. 2541-2552 ◽  
Author(s):  
Heidi D. Klepin ◽  
Arati V. Rao ◽  
Timothy S. Pardee

Treatment of older adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is challenging because of disease morbidity and associated treatments. Both diseases represent a genetically heterogeneous group of disorders primarily affecting older adults, with treatment strategies ranging from supportive care to hematopoietic stem-cell transplantation. Although selected older adults can benefit from intensive therapies, as a group they experience increased treatment-related morbidity, are more likely to relapse, and have decreased survival. Age-related outcome disparities are attributed to both tumor and patient characteristics, requiring an individualized approach to treatment decision making beyond consideration of chronologic age alone. Selection of therapy for any individual requires consideration of both disease-specific risk factors and estimates of treatment tolerance and life expectancy derived from evaluation of functional status and comorbidity. Although treatment options for older adults are expanding, clinical trials accounting for the heterogeneity of tumor biology and aging are needed to define standard-of-care treatments for both disease groups. In addition, trials should include outcomes addressing quality of life, maintenance of independence, and use of health care services to assist in patient-centered decision making. This review will highlight available evidence in treatment of older adults with AML or MDS and unanswered clinical questions for older adults with these diseases.


2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Lagadinou D. Eleni ◽  
Zoumbos C. Nicholas ◽  
Spyridonidis Alexandros

Whereas in younger patients diagnosed with acute myeloid leukemia (AML) treatment is straightforward and the goal is cure, the optimal treatment decision for older adults remains highly controversial. Physicians need to determine whether palliation, “something” beyond palliation, intensive therapy, or an investigational therapy is the most appropriate treatment option. This requires understanding of the biology and risk profile of the AML, clinical judgment in evaluating the functional status of the patient, communication skills in understanding the patient's wishes and social background, and medical expertise in available therapies. The physician has to accurately inform the patient about (a) the unique biological considerations of his leukemia and his prognosis; (b) the risks and benefits of all available treatment options; (c) novel therapeutic approaches and how the patient can get access to these treatments. Last but not least, he has to recommend a treatment. This paper tries to discuss each of these issues.


Leukemia ◽  
2004 ◽  
Vol 18 (4) ◽  
pp. 809-816 ◽  
Author(s):  
M A Sekeres ◽  
R M Stone ◽  
D Zahrieh ◽  
D Neuberg ◽  
V Morrison ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5722
Author(s):  
Maximilian Fleischmann ◽  
Ulf Schnetzke ◽  
Andreas Hochhaus ◽  
Sebastian Scholl

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.


Author(s):  
Michael Heuser ◽  
Alain Mina ◽  
Eytan M. Stein ◽  
Jessica K. Altman

Pretreatment somatic mutations influence acute myeloid leukemia (AML) pathogenesis and responses to chemotherapy. Integration of cytogenetic abnormalities and molecular mutations, co-occurring and in isolation, have resulted in a more refined prognostic assessment. In addition, research performed over the last few years has led to the development of novel therapies and new drug approvals in patients with both newly diagnosed and relapsed/refractory (R/R) AML. Here we discuss the use of these newly approved therapies. Advances in AML have also occurred through development of better tools to assess response to treatment. Both multiparameter flow cytometry and polymerase chain reaction can be used to assess for the presence or absence of measurable residual disease (MRD) and increase the sensitivity of response assessment. The role of MRD assessment is gaining relevance and its integration in clinical trials and treatment decision making will be explored in the second half of this article.


Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 51-56
Author(s):  
Alison R. Walker

Abstract Until recently, treatment options for patients with acute myeloid leukemia (AML) were limited to cytotoxic chemotherapeutic agents that possessed little specificity for the cytogenetic and molecular mutations known to risk stratify patients with this disease. With the approval of multiple new therapies, not only have the agents that we treat patients with changed, but the way we talk about these options, decide on, and manage therapy has also been transformed. Given these complexities, it is important that we help patients make an informed decision by weighing the risk of relapse with patient wishes and desired quality of life. Shared decision making (SDM) is an approach to medical decision making for those situations in which most clinicians would agree that there is more than 1 correct choice for a patient. Here we review the principles of SDM and provide an overview of the 3-talk model and how it may be incorporated into the care of patients with AML.


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