Improved Survival for AML Patients Enrolled in Clinical Trials

Given the lack of large population-based studies of patients with acute myeloid leukemia (AML), long-term data on the therapies these patients receive and long-term outcome are scarce. In a recent paper in Leukemia, Avinash G. Dinmohamed, MSc, BASc, from Erasmus MC Cancer Institute in Rotterdam, Netherlands, and colleagues conducted a nationwide population-based study of adult patients with AML to assess patterns of primary treatment, trial participation, and survival rates.

The researchers identified a total of 12,032 patients in the Netherlands who were diagnosed with AML between 1989 and 2012 (median age = 66 years; 54% male), as well as 585 patients with acute promyelocytic leukemia (APL; median age = 52 years; 47% male).

All patients were then categorized into four calendar periods (1989-1994, 1995-2000, 2001-2006, and 2007-2012) and four age groups (18-40, 41-60, 61-70, and >70 years of age) to determine if trial participation and survival changed according to age and time of diagnosis.

Data on the primary treatment for individual patients (including supportive care only, chemotherapy, and hematopoietic cell transplantation [HCT]) were taken from the Netherlands Cancer Registry.

The overall age-standardized incidence of AML and APL remained stable over time (3.0 per 100,000 and 0.15 per 100,000, respectively), the authors noted. Treatment including allogeneic HCT increased over time among non-APL AML patients younger than 70 while, for APL, the use of chemotherapy increased across all age groups over time (TABLE). Among patients older than 70, treatment remained conservative, with higher rates of supportive care only, the authors pointed out.

Allogeneic HCT was used more frequently than autologous HCT over time in patients with non-APL AML <70 years, with autologous HCT being applied in ~10 percent and allogenic HCT in 50 percent of patients. This increase was most pronounced among patients 41 to 60 years old, increasing from 8 to 46 percent from 1989 to 2012. Allogeneic HCT was gradually introduced in the treatment of patients 61 to 70 years old during the early 2000s.

Treatment of patients older than 70 years remained conservative, with supportive care remaining the therapy of choice for the majority of patients (ranging from 65% to 69% over time).

For patients with APL, use of chemotherapy gradually decreased as age increased:

  • 18-40 group: 77%
  • 41-60 group: 78%
  • 61-70 group: 75%
  • >70 group: 52%

“The data show that older patients are approached very differently by their doctors and are comparatively infrequently entered on clinical studies: Only 30 percent of patients between 61 and 70 years of age were enrolled in a trial and only 12 percent of patients >70 years,” Bob Löwenberg, MD, PhD, from Erasmus University Medical Center and a co-author of the study, told ASH Clinical News. “We are in need of new, more effective therapies which should come to us via clinical trials.”

Clinical trials participation in patients with non-APL AML was highest in the youngest cohort of patients, and decreased as age increased:

  • 18-40 group: 68%
  • 41-60 group: 57%
  • 61-70 group: 30%
  • >70 group: 11%

There were no trial data available for patients with APL.

Relative survival rates improved over time among both non-APL AML and APL patients. Between the first and last calendar periods (1989-1994 and 2007-2012), the five-year relative survival rates increased from 12 percent (95% CI 11%-14%) to 20 percent (95% CI 18%-21%) in patients with non-APL AML, and from 45 percent (95% CI 35%-54%) to 66 percent (95% CI 58%-74%) in patients with APL.

“For patients between 60 and 70 years old, one-year survival is more than 40 percent and five-year survival is 14 percent, which argues for actively offering these patients therapy,” Dr. Löwenberg added. “One of the unmet needs in the treatment of AML concerns patients at advanced age. Treatment outcomes in older patients is still highly unsatisfactory.”

“Survival over the past two decades has increased, which may be explained by the increased use of intensive and potentially curative treatment over time,” Dr. Dinmohamed and authors wrote. “As survival remained poor for older AML patients over the last two decades, clinical trials and active participation in those trials are warranted to explore innovative treatment strategies for this elderly population,” the authors concluded.

There are some limitations of the study to note, including changes in classification and registration practice over time. “Detailed data on clinical (for example, comorbidity and performance status) and disease-related characteristics (for example, cytogenetics and molecular analysis) are not yet available in the Netherlands Cancer Registry,” the authors added.


Reference

Dinmohamed AG, Visser O, van Norden Y, et al. Treatment, trial participation and survival in adult acute myeloid leukemia: a population-based study in the Netherlands, 1989-2012. Leukemia. 2015 July 17. [Epub ahead of print]

TABLE. Use of Therapy for Patients with Non-APL AML According to Age Group
18-40 years 41-60 years 61-70 years >70 years
Supportive care only 11% 12% 29% 70%
Chemotherapy 40% 52% 64% 29.5%
Autologous HCT 15% 10% <1% N/A
Allogeneic HCT 38% 27% 7% N/A

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