Abstract
Acute myeloid leukemia (AML), with an incidence increasing with age, is the most common acute leukemia in adults. Concurrent comorbidities, mild to severe organ dysfunctions, and low performance status (PS) are frequently found in older patients at the onset, conditioning treatment choice and crucially influencing the outcome. Although anthracyclines plus cytarabine-based chemotherapy, also called “7 + 3” regimen, remains the standard of care in young adults, its use in patients older than 65 years should be reserved to selected cases because of higher incidence of toxicity. These adverse features of AML in the elderly underline the importance of a careful patient assessment at diagnosis as a critical tool in the decision-making process of treatment choice. In this review, we will describe selected recently approved drugs as well as examine prognostic algorithms that may be helpful to assign treatment in elderly patients properly.
Highlights
Acute myeloid leukemia (AML), with a yearly incidence in Europe of 5–8 cases per 100,000 individuals, is cancer predominantly of the elderly, with a median age at diagnosis of 67 years [1].In the last decades, unlike for young adults, overall survival (OS) has not changed meaningfully for the elderly ones, with less than 10% of patients older than 65 years being alive 5 years after the diagnosis [2].Considering that the life expectancy of people aged 65 in the Western world is of approximately 15–20 additional years, the negative social impact of AML is evident [3]
Double-blind placebo-controlled, Phase III study that enrolled 717 adult patients (18–59 years of age) with newly diagnosed AML carrying FLT3 mutations, the association of midostaurin/placebo plus a standard induction chemotherapy followed by midostaurin/placebo maintenance showed a clear advantage for the midostaurin containing arm (EFS, 8.2 months versus 3.0 months, p = 0.002; disease-free survival (DFS), 26.7 months versus 15.5 months, p = 0.01; OS, 74.7 months versus 25.6 months, p = 0.009)
The results of this trial led to the approval of midostaurin by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), “in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy, and for patients in complete response followed by Midostaurin single-agent maintenance therapy, for adult patients with newly diagnosed acute myeloid leukemia who are FLT3 mutation-positive”
Summary
Acute myeloid leukemia (AML), with a yearly incidence in Europe of 5–8 cases per 100,000 individuals, is cancer predominantly of the elderly, with a median age at diagnosis of 67 years [1]. The biological and cytogenetic profile of elderly patients with AML differs from that of the young with a major incidence of unfavorable cytogenetics [6], of secondary AML supervening after previous hematological disorders like myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN), or following exposure to radio-chemotherapy (therapy-related AML) [5]. All these elements explain the poor outcome of AML of older/elderly patients, pointing out the importance of delivering as personalized as possible treatment strategies supplanting the conventional “one-size-fits-all” approach. We believe this is a critical step since availability of non-intensive, effective options raises the issue as to whether intensive chemotherapy remains a choice of significance for older patients with AML
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