Only adult patients with acute myeloid leukemia (AML) aged 50 years and older showed significant improvements in overall survival (OS) from 2000 to 2016, according to results of a retrospective, population-based study conducted in Denmark. These findings were presented during the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.

AML is a clinically and genetically diverse disease associated with a poor prognosis. The estimated median OS for patients diagnosed with AML who are younger than 60 years is less than 3 years and for patients who are diagnosed at age 60 years or older it is less than 1 year. With a median age at diagnosis of approximately 70 years, AML is typically diagnosed in older adults.

Over the last several years, a number of targeted therapies have been approved (eg, FLT3 and IDH inhibitors) or reapproved (eg, gemtuzumab ozogamicin, an anti-CD33 antibody drug conjugate) for the treatment of patients with AML, with the development of novel agents largely driven by an increased understanding of the molecular landscape of the disease. While few new treatments were approved in the setting of AML in the 15 years preceding these recent drug approvals, a number of advancements in routine clinical practice regarding the delivery of chemotherapy, supportive care, and the use of allogeneic hematopoietic stem cell transplantation (ASCT) were made during that period of time.

The primary aim of this study was to examine the temporal change in OS for adult patients with AML included in the Danish National Acute Leukemic Registry who were diagnosed with the disease between 2000 and 2016. In addition, trends in treatment strategy since 2000 were also examined.

Of the 3825 patients included in the overall study cohort, the 2-year OS rates for patients diagnosed with AML between 2000 to 2006, 2007 to 2011, and 2012 to 2016 were not significantly different at 26%, 24%, and 25%, respectively. However, an analysis of patient age at the time of AML diagnosis within these time periods showed an increase in the proportion of patients aged 60 years and older from 2000 to 2006 and 2012 to 2016. While only 27% of patients were 75 years or older in 2000 to 2006, this percentage increased to 36% in 2012 to 2016.

Age-standardized survival analyses showed improvements in OS over time for the subgroup of patients aged 50 years and older at the time of their AML diagnosis. Specifically, the respective rates of 2-year OS in 2002 and 2016 were 41% and 58% for patients aged 50 to 59 years at AML diagnosis (P =.03). The same rate was 21% and 32% for those diagnosed with AML at age 60 to 75 years (P =.009). In contrast, no significant change in 2-year OS rate was observed for patients aged 40 to 49 years (P =.4), and there was a very limited increase in the rate of 2-year OS observed for patients older than 75 years at time of AML diagnosis (P =.046).

For each patient included in the analysis, the most intensive therapy received within 30 days of diagnosis was classified as either intensive (ie, corresponding to therapy that could induce disease remission), nonintensive (eg, low-dose cytarabine or azacitidine), or palliative/no treatment.

Intensive therapy was administered to 53%, 49%, and 44% of study patients during the years 2000 to 2006, 2007 to 2011, and 2012 to 2016, respectively. However, within this group of 1872 patients, there was a substantial increase in the proportion of patients in the 50 to 59 year age subgroup receiving intensive therapy 82.5% during 2000 to 2006 and 92.3% during 2012 to 2016. There was also an increase in the proportion of patients achieving complete remission (CR) following administration of the first or second course of intensive chemotherapy when comparing 2012 to 2016 with 2000 to 2016 (76% vs 71%, respectively; P =.09). These findings translated into a significant improvement in OS (P =.004), which, on age-adjusted survival analyses, was observed for patients between 50 and 75 years treated with intensive therapy.

Whereas only 8% of patients achieving a CR with intensive chemotherapy were referred for ASCT from 2000 to 2006, with a corresponding median age of 46 years, this percentage increased to 28% from 2012 to 2016 (P <.001) and the median age of these patients was 58 years.

Nonintensive chemotherapy was the most intensive therapeutic approach within 30 days of AML diagnosis for 14% of patients from 2012 to 2016 compared with only 3% of patients from 2000 to 2006, and this temporal trend was particularly notable in patients older than 75 years at the time at AML diagnosis, with 21% undergoing nonintensive therapy in the more recent time interval compared with only 3.8% in 2000 to 2006.

Palliative treatment/no treatment was the most intensive therapeutic approach in approximately 40% of patients in between 2000 to 2006 and 2012 to 2016.

In summarizing the results of this study, the presenting author Lasse Jakobsen, PhD, of the Department of Hematology at Aalborg University Hospital in Denmark, stated that when looking specifically at patients between 50 and 75 years of age, we observed a large increase in 2-year OS, which may be attributable to increased use of stem cell transplantation and non-palliative treatment. He also noted that an improvement in selection for both intensive and nonintensive therapies may also contribute to the increase.

Although we observed a significant improvement in OS among the very elderly patients, this improvement was rather limited and these patients still have a very poor outcome, Dr Jakobsen concluded.

Read more of Cancer Therapy Advisors coverage of the EHA virtual meeting by visiting the conference page.

Reference

Jakobsen LH, Roug AS, vlisen AK, et al. Temporal trends in overall survival among adult non-APL AML patients in the period 2000-2016: A Danish population-based study. Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S145.

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Real World Evidence Shows OS Improvements in Older Patients With AML From 2000 to 2016 - Cancer Therapy Advisor