Increase in Chemotherapy Use and Associated Survival Benefit Among Medicare-Aged Patients with Acute Myeloid Leukemia (AML)

Introduction: The incidence of AML increases with age and more than half of patients are diagnosed at age ≥ 65 years. The prognosis of patients aged ≥ 65 years is very poor and worsens with advancing age as treatment efficacy and tolerability have been shown to deteriorate markedly with age. The objective of this analysis was to examine treatment trends over time, factors predictive of therapy receipt and prognosis, and overall survival in an elderly AML population in routine clinical practice.

Methods: This retrospective analysis utilized linked cancer registry claims data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1, 2000 to December 31, 2013, with Medicare enrollment and claims data through 2015, thus allowing a minimum 2-year follow-up. Patients were included if they were diagnosed with a first primary AML cancer, were aged > 66 years, and continuously enrolled in Medicare Parts A and B with no health maintenance organization (HMO) coverage in the year prior to diagnosis. Differences in patient characteristics by treatment status were assessed with the chi-square test for categorical variables and analysis of variance (ANOVA) or t-test for continuous variables. Unadjusted Kaplan-Meier survival curves with accompanying log-rank test were generated. A time-varying Cox proportional hazards regression model examined the relative risk of death by treatment status, adjusting for age, sex, race, prior myelodysplastic syndromes (MDS), poor performance indicators (PPIs), comorbidity burden, income, education, marital status, year of diagnosis, and geographic region.

Results: Of the 11,142 patients analyzed in the study, 4,772 (43%) patients received treatment with chemotherapy within 3 months of diagnosis and 6,370 (57%) patients did not receive treatment. Treatment rates increased over the study time period from 36% in 2000 to 55% in 2013 (P < 0.0001; Figure 1). The mean age at diagnosis was 75 years for treated patients and 80 years for untreated patients (P < 0.0001). Forty-three percent of treated patients were over the age of 75 years at diagnosis compared with 74% of untreated patients. Treated patients were more likely to be male (54% vs 50%), be married (60% vs 46%), to have a lower incidence of prior MDS (14% vs 19%), were less likely to have PPIs (8% vs 19%), and had a lower comorbidity burden (54% vs 43% with a comorbidity score of 0) compared with untreated patients. The median unadjusted overall survival was 2.13 months for the overall population and was longer for treated patients (5.3 months) compared with untreated patients (1.6 months; log-rank P < 0.0001). In multivariate survival analysis, treated patients exhibited a 14% lower risk of death compared with untreated patients (hazard ratio 0.86; 95% CI 0.81-0.91). Patients receiving treatment within 30 days of diagnosis had a 67% reduction in 30-day mortality risk and a 41% reduction in 60-day mortality risk compared with those who did not receive treatment. Advanced age, higher comorbidity score, presence of PPIs, and being unmarried were significantly associated with higher mortality risk.

Conclusions: Use of chemotherapy among the elderly AML patient population has increased over time. However, at the time of the analysis, about 45% of patients were still not receiving treatment, and the rate of undertreatment was even more pronounced among those aged > 75 years. The use of antileukemic therapy was associated with a significant survival benefit compared with palliative care, after controlling for age, comorbidities, poor performance, and other patient characteristics. An unmet treatment need among older AML patients persists.

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