Trends In Outcomes In Core Binding Factor Acute Myeloid Leukemia: A SEER Database Analysis
Authors: Brunner Andrew M. , Blonquist Traci , Sadrzadeh Hossein , Chen Yi-Bin , Neuberg Donna S. , Fathi Amir T. 
Published: October 2019

Abstract

Acute myeloid leukemia with chromosomal alterations impacting the core binding factor transcription complex (CBF-AML), specifically t(8;21) and inv(16), are associated with a greater responsiveness to cytarabine-based chemotherapies and a more favorable prognosis. The latter has been primarily gleaned from outcomes of large clinical trials of AML. However, to date, there is limited population-based outcomes data on CBF-AML. We therefore performed an epidemiologic retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database to assess survival trends for CBF-AML at the population level between 2000 and 2010.

Patients and Methods
Patients with a diagnosis of CBF-AML between 2000 and 2010 were identified using the SEER 18 registries database. We included patients with a diagnosis code of inv(16)/t(16;16) AML (Code 9871) or t(8;21) AML (Code 9896) diagnosed between January 2000 and December 2010. Patients were divided into cohorts based on age at diagnosis: 15-44 years old, 45-64 years old, 65-74 years old, and 75-84 years old. Disease incidence was calculated, as were early mortality rates, defined as death within 1 month. Overall survival (OS) was estimated using the method of Kaplan and Meier. Cox regression was performed to estimate predictors of survival by specific CBF-AML type, age cohorts, race/ethnicity, gender, year of diagnosis, number of primary malignancies, and residence.

Results
We identified 777 patients with a new diagnosis of CBF-AML between 2000 and 2010. The incidence of CBF-AML increased with advancing age (ages 15-44, 0.06 per 100,000 people; ages 45-64, 0.13; ages 65-74, 0.25; ages 75-84, 0.28). Median OS for all patients was 22 months, and the combined 3-year OS was 44.3% (Fig. 1). Median OS increased from 16 months during the period encompassing 2000 and 2002 to 25 months during the period from 2006 to 2008 (p=0.002) (Fig. 2). The rate of early death was 13%, which increased with age (15-44 5%, 45-64 10%, 65-74 20%, 75-84 33%; P<0.0001). OS also worsened with advancing age; patients ages 75-84 had a 3 year OS of 9.3% and an increased HR for mortality compared to patients ages 15-44, who had a 3 year OS of 68.7% (HR 5.61, P<0.0001) (Fig. 3). Of note, worsening OS with advancing age was observed even among the subset of patients alive at 1 month. Black race was associated with an increased HR for mortality compared to white non-Hispanic patients (HR 1.50, P=0.03). Patients with inv(16) disease had an improved OS compared to patients with t(8;21) disease (HR for mortality 0.65, P<0.0001). The 3 year OS for patients with inv(16) disease was 57.3%, while for those with t(8;21) disease it was only 35.5% (Fig. 1).

Conclusion
In spite of historically favorable prognoses associated with CBF-AML in clinical trials, we found poorer survival in the general population. Unlike inv(16) disease, patients with t(8;21) CBF-AML did not appear to have a favorable OS. Survival was significantly worse among African Americans and the elderly. The reason for these differences is unknown, and merits further evaluation.

Disclosures:
Chen: Otsuka Pharmaceuticals, Inc.: Research Funding; Seattle Genetics: Consultancy, Research Funding; Bayer / Onyx: Research Funding. Fathi:Seattle Genetics: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Teva: Membership on an entity’s Board of Directors or advisory committees; Agios: Membership on an entity’s Board of Directors or advisory committees; Millenium: Research Funding.