Trends in All-Cause Mortality Among Older Patients with CML: A SEER Database Analysis

Clinical outcomes for patients with chronic myeloid leukemia (CML) have dramatically improved over the course of the past ten years, following the advent of tyrosine kinase inhibitors (TKIs) that target BCR/ABL. Nonetheless, survival differences persist between age groups. Prior analyses suggested that this difference occurs in part due to treatment variation; in Sweden, patients older than age 79 had poorer relative survival, and more typically were treated with hydroxyurea rather than a TKI [Bjorkholm, J Clin Oncol 29:2514]. Other studies have noted gains made in relative survival up to the year 2004 [Brenner, Haematologica93:1544], but longer-term overall survival following the widespread use of TKI therapy is less well described among older patients in the U.S. We performed an epidemiologic study of patients registered in the Surveillance, Epidemiology, and End Results (SEER) database to estimate the 5 year overall survival (OS) of patients treated for CML in the era of TKI therapy to assess for differences in survival outcomes among patients within different age groups.

Patients with a diagnosis of CML were identified using the SEER 19 registries database [www.seer.cancer.gov, 1973–2009, November 2011 submission]. We included patients with a diagnosis code of CML NOS (Code 9863) and BCR/ABL+ CML (Code 9875) diagnosed between January 2000 and December 2005. This interval brackets the FDA approval of imatinibin 2001, and its incorporation into NCCN guidelines in 2003. To reflect the evolution of CML treatment during this interval, we trended 5-year overall survival by the year of initial diagnosis. To evaluate the effect of age on survival, 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. Overall survival was estimated using the method of Kaplan and Meier. Cox proportional hazards regression was used to model OS to estimate the effects of year of diagnosis within each age group. All analyses were performed using SAS statistical software.

We identified 5,138 patients registered in the SEER database with a new diagnosis of CML between January 2000 and December 2005. The patients were 57.6% male; this was the first recorded primary malignancy for 88.4% of the cohort. The 5-year OS improved among patients in every age group between the years 2000 and 2005 (Table 1, Figure 1). Compared to patients diagnosed in the year 2000, patients between the ages of 15 and 44 years had the greatest improvement in 5 year OS (Figure 1; hazard ratio (HR) for dying 0.427, 95% CI: [0.278;0.655], P<0.0001). Patients between ages 75 and 84 also had significant survival gains; the OS estimate at 5 years increased from 19.2% in 2000 to 36.4% in 2005 (HR for dying 0.571, 95% CI: [0.443;0.736], P<0.0001).

Tyrosine kinase inhibitors targeting BCR/ABL have been FDA-approved for the treatment of CML since 2001 and are highly effective therapy for this disease. Since their advent, patient survival has improved among all age groups; intriguingly, this is also seen among older patients. Indeed, we found marked improvements in OS at 5 years among patients between the ages of 75 and 84, a group which historically has had very poor outcomes. Our data suggests that the advent of BCR/ABL tyrosine kinaseinhibitors has had a significant impact on the outcomes of older patients with CML, likely by providing them with tolerable and effective treatment options not previously available. Further study is needed to determine specific factors that contribute to this improvement in survival. In the future, older age groups are likely to experience ongoing benefit from novel and effective therapeutics with tolerable side effect profiles.

Figure 1.

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Estimated rates of overall survival (proportion alive) at 5 years by age group and year of diagnosis.

Figure 1.

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Estimated rates of overall survival (proportion alive) at 5 years by age group and year of diagnosis.

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Fathi:Teva Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees.