Exploring Treatment for Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is an aggressive type of blood cancer in which the bone marrow makes abnormal myeloblasts, or immature white blood cells, resulting in low healthy white cell count. AML is also sometimes referred to as acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute nonlymphocytic leukemia.¹ 

AML is the most common acute leukemia in adults with an estimated 21,450 new cases expected in 2019 in the United States and approximately 10,920 deaths.² Patients with existing blood disorders, such as myelodysplastic syndrome or inherited syndromes ,may be more likely to be diagnosed with AML, but symptoms for the cancer are often non-specific. A patient may present with weight loss, fatigue, fever, night sweats, or loss of appetite. However, if the AML has advanced to the point of leukostasis, a patient’s symptoms could resemble those similar to a stroke including headaches, weakness on one side of the body, slurred speech, confusion, and sleepiness.³ 

FAST DIAGNOSIS IS KEY 

Prognosis varies widely due to speed of diagnosis and age of patients. Being more prevalent among adults, the incidence of AML increases with age, from 1.3 per 100,000 patients less than 65 years old to 12.2 cases per 100,000 in those over 65 years.⁴ 

Diagnosis of AML could include a number a number of tests, but the time between diagnosis to treatment is crucial. Tests for diagnosis could include biopsy, blood panels, bone marrow aspiration and biopsy, molecular and genetic testing, imaging, and lumbar puncture.⁵ 

Both the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines recommend including complete blood count tests with a routine chemistry profile, coagulation profiles, and molecular testing for c-KIT, FLT3-ITD, NPM1, CEBPA, and other mutations for patients presenting with possible AML.⁶ 

TREATMENT OPTIONS 

Treatment for most patients with AML can be divided into two main chemotherapy phases—remission induction (induction) and consolidation (post remission therapy).⁷ As this particular kind of cancer can progress rapidly, treatment needs to be started immediately. 

According to the National Cancer Institute, recent advancements in the treatment of AML have resulted in significant improvements in patient complete remission (CR) rates. Induction therapy has proven effective with 60% to 70% of adults with AML achieving CR status following treatment.² 

According to a JAMA study, the United States Food and Drug Administration (FDA), approved 2 new AML treatments: for older adults who cannot undergo intensive chemotherapy and one for patients with a specific genetic mutation. Glasdegib tablets are indicated for use in combination with low doses of chemotherapy medication cytarabine in adults aged 75 years or older with newly diagnosed AML. Gilteritinib tablets were approved for patients presenting with the FLT3 gene mutation, who are prone to more aggressive forms of AML and at higher risk of relapse.⁸ 

This approval was based on a recent clinical trial for adults with relapsed or refractory AML. Participnts in the trial were randomized in a 2:1 ratio to receive gilteritinib 120 mg once daily (n = 247) for continuous 28-day cycles or salvage chemotherapy, which included intensive cytotoxic chemotherapy or a low-intensity regimen (n = 124). OS was measured from date of randomization through to death by any cause. The median OS was 9.3 months and 5.6 months for patients receiving gilteritinib and those in the chemotherapy arm, respectively (hazard ratio [HR], 0.64; 95% CI, 0.49-0.83; 1-sided P value = .0004). These findings were consistent in the intensive chemotherapy (HR, 0.66; 95% CI, 0.47-0.93) and low-intensity regimen (HR, 0.56; 95% CI, 0.38-0.84) stratums.⁹ 

Although advances in the treatment of AML have led to significant improvements in outcomes for younger patients, prognosis in the elderly, who account for the majority of new cases, remains poor. Even with current treatments, as much as 70% of patients 65 years or older will die of their disease within 1 year of diagnosis.² 

A study published in 2010 set the cost of induction therapy at $63,000. In a similar study, health care costs and utilization during the first year after a diagnosis of AML for privately insured non- Medicare patients in the United States aged 50 to 64 years who were treated with either chemotherapy or chemotherapy and allogeneic hematopoietic cell transplantation (alloHCT), were estimated based on MarketScan (Truven Health Analytics) adjudicated total payments for inpatient, outpatient, and prescription drug claims from 2007 to 2011. Adjusted mean 1-year costs were $280,788 for chemotherapy and $544,178 for alloHCT.¹⁰ 

 References 

1. National Cancer Institute. Adult acute myeloid leukemia treatment (PDQ)–patient version. 2019.https://www.cancer.gov/types/leukemia/ patient/adult-aml-treatment-pdq. Updated October 19, 2018. Accessed June 7, 2019. 
2. National Cancer Institute. Adult acute myeloid leukemia treatment (PDQ)–health professional version. 2019. https://www.cancer.gov/types/ leukemia/hp/adult-aml-treatment-pdq. Updated February 8, 2019. Accessed June 7, 2019. 
3. American Cancer Society. Acute myeloid leukemia in adults. https://www.cancer.org/cancer/ acute-myeloid-leukemia/detection-diagnosis-staging/detection.html. Revised August 21, 2018. Accessed June 7, 2019. 
4. De Kouchkovsky I, Abdul-Hay M. 'Acute myeloid leukemia: a comprehensive review and 2016 update'. Blood Cancer J. 2016;6(7):e441. doi:10.1038/bcj.2016.50 
5. Cancer.net Editorial Board; American Society of Clinical Oncology (ASCO). Leukemia - Acute Myeloid – AML: Diagnosis. cancer.net website. Published June 2016. https://www.cancer.net/ cancer-types/leukemia-acute-myeloid-aml/ diagnosis. Accessed June 11, 2019. 
6. Seiter K. Acute myeloid leukemia (AML) guidelines. Medscape. May 10, 2019. https:// emedicine.medscape.com/article/197802- guidelines#g1. Accessed June 11, 2019. 
7. American Cancer Society. Typical treatment of acute myeloid leukemia (Except APL). https:// www.cancer.org/cancer/acute-myeloid-leukemia/treating/typical-treatment-of-aml.html. Updated May 3, 2019. Accessed June 7, 2019 
8. Voelker R. New acute myeloid leukemia therapy. JAMA. 2019;321(1):23. doi:10.1001/ jama.2018.20416. 
9. US Food and Drug Administration. FDA approves addition of survival data to gilteritinib label for refractory AML with a FLT3 mutation. fda.gov website. https://www.fda.gov/drugs/ resources-information-approved-drugs/fda-approves-addition-survival-data-gilteritinib-label-refractory-aml-flt3-mutation. Updated May 30, 2019. Accessed June 11, 2019. 
10. Cardarelli WJ. The evolution of care for acute myeloid leukemia and the challenges of defining value. J Clin Pathways. 2018;4(suppl 1):S28-S34. doi:10.25270/jcp.2018.05.00014.