AML Survival: Changes over 3 Decades
Abstract & Commentary
By William B. Ershler, MD
Synopsis:In an epidemiological evaluation of acute myeloid leukemia survival over 3.5 decades, dramatic improvement was demonstrable for younger patients, but not so for the elderly. The data are consistent with data recently published from Sweden and the United States. In this disease that occurs most frequently in geriatric populations, there is a great need for developing more effective treatment strategies.
Source: Shah A, et al. Survival and cure of acute myeloid leukemia in England, 1971-2006: A population-based study. Br J Haematol 2013;162:509-516.
Acute myeloid leukemia (AML) accounts for approximately 80% of all acute leukemia in
adults and its incidence has remained fairly stable over the past several decades except for a fairly dramatic increase in its occurrence in patients 75 years and older,1a finding that may reflect improved diagnostic techniques and registration. However, with the demographic changes currently upon us and with this increased recognition of AML in the elderly, the median age at diagnosis is currently 70 years.2,3It is estimated that 13,780 individuals were diagnosed with AML in the United States in 2012, and that 10,200 will die of the disease.1The incidence increased from two to three per 100,000 in young adults to 13 to 15 per 100,000 in the seventh and eighth decades of life.4
There has been a sense that the developments in AML management including standardized chemotherapeutic approach, the selective use of novel targeted agents, and improved supportive management have resulted in improved survival.5,6However, most reports examining survival are derived from clinical trials that include younger and functionally more capable patients, and these may not reflect the general population of AML patients.7To get a sense of the magnitude of improvement in treatment success for the general population of AML patients, Shah and colleagues presented epidemiological data derived from cancer registries throughout England. This population-based study estimated the 5-year relative survival and "cure" for 48,380 adult patients diagnosed with AML in England during 1971-2006. Taking a statistical perspective, "cure" was defined as when AML patients experience the same mortality as individuals without AML who have similar demographic characteristics. The authors argue that "cure" models facilitate greater insights into the outcome of patients than survival alone. The aim of this study was to evaluate trends in population-based survival (measured by 5-year relative survival), the percentage "cured," and the median survival time of the "uncured" for adult patients diagnosed with AML in England during 1971-2006.
The analysis indicated the 5-year relative survival and the percentage "cured" increased for patients aged < 70 years at diagnosis during 1971-2006, but advancing age remained associated with poorer outcome. During the study period, a dramatic increase in 5-year relative survival occurred in those aged 15-24 years, from 7% to 53%. The percentage "cured" was < 10% for all ages in 1975, but increased to 45% for those aged 15-24 years in 2000. Cure could not be estimated for patients > 70 years, because survival was consistently low (< 5%).
As a reader unaccustomed to thinking of "cure" in an epidemiologic sense, I found the current report to be both refreshing and enlightening. Certainly, over these three and one-half decades, the long-term outcome for patients with AML has improved substantially, but notably, only for younger patients. And, even for younger patients, there remains room for improvement.
The data presented are comparable to a similar population-based analysis of AML "cure" conducted in Sweden for patients diagnosed between 1973-2001.8The percentage "cured" was < 7% for all patients in 1975, which increased to 68% in patients aged 19-40 years at diagnosis and to 8% in patients aged 61-70 years by 2000. Similarly, Thein and colleagues examined the NCI SEER database and examined overall AML survival by decade for different age groups.9In that analysis, there was modest 2-year survival improvement for those aged 65-74 years over the 3 decades (from 10% to 17%), but no survival improvement over the same period for those aged ≥ 75 years.
Thus, as anticipated by the published results from clinical trials, there is epidemiological evidence for improvement in survival and even cures (defined epidemiologically) over the past 3 decades. However, the data also highlight the discouraging lack of survival improvement for older patients. What accounts for this remains to be established, but explanations probably include the inability or reluctance to use standard chemotherapy schedules as well as tumor-related factors such as less favorable cytogenetics and prior myelodysplasia, both of which are more common in the elderly. Nonetheless, as the population ages, an increased emphasis on developing effective AML treatment for older patients is in order. Age-specific clinical trials, such as the European trial of clofarabine for elderly AML patients,10will hopefully result in epidemiological evidence for improved survival for the population as a whole.
- Siegel R, et al. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.
- Estey E, Dohner H. Acute myeloid leukaemia. Lancet 2006;368:1894-1907.
- Phekoo KJ, et al. The incidence and outcome of myeloid malignancies in 2,112 adult patients in southeast England. Haematologica 2006;91:1400-1404.
- Lowenberg B, et al. Acute myeloid leukemia. N Engl J Med 1999;341:1051-1062.
- Dohner H, et al. Diagnosis and management of acute myeloid leukemia in adults: Recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453-474.
- Grimwade D, Hills RK. Independent prognostic factors for AML outcome. Hematology Am Soc Hematol Educ Program 2009:385-395.
- Hills RK, Burnett AK. Applicability of a "Pick a Winner" trial design to acute myeloid leukemia. Blood 2011;118:2389-2394.
- Andersson TM, et al. Temporal trends in the proportion cured among adults diagnosed with acute myeloid leukaemia in Sweden 1973-2001, a population-based study. Br J Haematol 2010;148:918-924.
- Thein MS, et al. Outcome of older patients with acute myeloid leukemia: An analysis of SEER data over 3 decades. Cancer 2013;119:2720-2727.
- Burnett AK, et al. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol 2010;28:2389-2395.