What is Acute Myeloid Leukemia (AML)?

From the Guidelines

Acute Myeloid Leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues, requiring prompt treatment to improve morbidity, mortality, and quality of life.

Overview of AML

• AML is the most common form of acute leukemia among adults, with an estimated 19,940 people diagnosed in 2020, and 11,180 patients dying of the disease 1.
• The disease is more common in older adults, with approximately 54% of patients diagnosed at age ≥65 years, and a median age at diagnosis between 68 and 71 years of age 1.
• AML can be subclassified into several categories, including acute promyelocytic leukemia (APL), and recently, a new category of myeloid neoplasms with germline disposition was suggested 1.

Treatment of AML

• Treatment of AML is divided into initial remission-induction chemotherapy, postremission or consolidation therapy, and maintenance therapy, using oral azacitidine for patients who are unable to complete intensive curative therapy 1.
• The goal of treatment is to achieve complete remission, and the choice of treatment depends on the patient's age, overall health, and specific genetic characteristics of the leukemia cells.
• Advances in sequencing techniques have broadened our understanding of the molecular basis of AML, increasing the number of treatment options, including new targeted agents, like venetoclax, and alternative formulations of existing therapies 1.

Risk Assessment and Prognosis

• Risk assessment in AML includes the patient's age, initial leukocyte count, AML subtype, karyotype data, and selected molecular markers 1.
• AML with certain chromosomal translocations, such as t(15;17), t(8;21), and t(16;16), are considered favorable, while an antecedent or concomitant myelodysplastic syndrome or complex aberrant karyotype are adverse prognostic factors 1.
• The evaluation of measurable or minimal residual disease (MRD) is an important part of refining posttreatment risk stratification, and individualization of treatment and supportive care is essential to improve patient outcomes 1.

From the FDA Drug Label

RYDAPT is indicated in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by an FDA approved test RYDAPT in combination with chemotherapy was investigated in a randomized, double-blind placebo-controlled trial of 717 patients with newly-diagnosed FLT3-mutated AML.

Acute Myeloid Leukemia (AML) is a type of cancer that affects the blood and bone marrow. It is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells.

• Key points:
  • AML is a type of blood cancer
  • It affects the bone marrow and blood cells
  • Abnormal white blood cells accumulate in the bone marrow
  • Interferes with the production of normal blood cells
  • Can be treated with chemotherapy and targeted therapy, such as midostaurin (RYDAPT) in combination with standard chemotherapy for patients with FLT3 mutation-positive AML 2, 2, 2

From the Research

Definition and Overview of Acute Myeloid Leukemia (AML)

• Acute Myeloid Leukemia (AML) is the most common acute form of leukemia in adults, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells 3, 4.
• AML is a bone marrow stem cell cancer that is often fatal despite available treatments, with a poor long-term survival rate and a high relapse rate 5.
• The diagnosis of AML is based on the presence of immature leukemia cells in the blood, bone marrow, or extra-medullary tissues, and new biological insights have been integrated into recent classification systems 5.

Treatment and Management of AML

• The current standard induction regimen for AML is a combination of daunorubicin and cytarabine, known as the '3 + 7' regimen, which has remained essentially unaltered over the last 40 years 3.
• However, genetic risk stratification should be used to determine patients who are unlikely to respond to standard intensive chemotherapy, and these patients should be enrolled in clinical trials upfront 3.
• Newer agents, such as CPX-351 and midostaurin, have been approved for the treatment of AML, and the incorporation of measurable residual disease (MRD) findings into therapeutic decision-making is rapidly evolving 3, 5.
• The treatment approach for AML should integrate patient and caregiver goals of care, comorbidities, and disease characteristics, and clinicians should be able to recognize the early signs of AML and ensure prompt treatment 4, 5.

Prognosis and Risk Factors

• The prognosis for AML patients is generally poor, with a 5-year overall survival rate of less than 35% in younger patients and even lower in older patients 4, 6.
• Risk factors for very early death within 30 days after diagnosis include older age, low hemoglobin levels, low estimated glomerular filtration rate, and low Glasgow Coma Scale score 7.
• A multivariate analysis revealed that older age, low hemoglobin levels, and low Glasgow Coma Scale score are significantly associated with very early death in AML patients 7.

Recent Advances and Future Directions

• The US Food and Drug Administration has approved several new agents for the treatment of AML since 2017, including venetoclax, FLT3 inhibitors, and IDH inhibitors 6.
• Ongoing research in AML is progressing rapidly, with a focus on improving treatment outcomes and developing more effective therapeutic strategies 6.
• The incorporation of newer agents and strategies into traditional AML chemotherapy is evolving, and maintenance therapy now has a definite role in the treatment of AML 6.