Abstract
Introduction: Conventional intensive chemotherapy remains the standard of care for younger, functionally fit patients with AML, whereas patients with advanced age, poor performance indicators (PPIs), and/or increased comorbidity burden are often untreated or treated with less intensive chemotherapy and DNA hypomethylating agents (HMAs). Survival outcomes among these patients have not improved over several decades, and there is a scarcity of data on the comparative effectiveness of AML chemotherapies at the population level. We sought to describe the treatment patterns and associated survival outcomes of older AML patients in a real-world setting.
Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to obtain a cohort of elderly patients diagnosed with AML. Patients included in the study fulfilled the following eligibility criteria: diagnosed with a first primary AML between January 1, 2000 and December 31, 2013, aged > 66 years, and continuously enrolled in Medicare Part A and B in the year prior to diagnosis. The data set included Medicare claims data available up to the year 2015, which allowed a minimum 2 years of follow-up time. The study included 11,142 patients, of which 6,370 (57%) did not receive treatment within 3 months of diagnosis. Of those initiating treatment, 936 (8%) were treated with azacitidine and/or decitabine (HMA), 153 (1%) were treated with a cytarabine combination regimen (Intensive), 433 (4%) received another type of agent (Other) and 3,250 (29%) received an unidentified agent (Unknown). The Unknown group received their treatment during an inpatient stay, and claims for inpatient stays are paid based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis or procedures codes and not chemotherapy J codes. It is possible that these "Unknown" therapies are indicative of an intensive regimen that needed to be administered in a controlled inpatient setting. To compare patient characteristics by treatment type, the chi-square test for categorical variables and analysis of variance (ANOVA) or t-test for continuous variables were used. Unadjusted Kaplan-Meier survival plots and corresponding log-rank test were used to compare overall survival by treatment type. Cox proportional hazards regression modeling estimated the relative risk of death adjusting for demographic and clinical factors.
Results: Use of HMA therapies significantly increased from 2% in 2005 to 22% in 2013, whereas the untreated rate significantly decreased during that same time period, from 63% in 2005 down to 45% in 2013. Rates of Intensive therapy remained fairly consistent throughout the entire study period. There were similarities in demographic and clinical characteristics between patients receiving Intensive and Unknown therapies and between patients receiving HMA and Other therapies (Table 1). Patients receiving Intensive chemotherapy and Unknown therapy were younger, had lower comorbidity burden, and were less likely to have prior myelodysplastic syndromes (MDS) or PPIs. The median unadjusted overall survival was longest for patients receiving Intensive therapy (16.7 months), followed by HMA therapy (7.3 months), Unknown therapy (4.5 months), Other therapy (3.5 months), and was shortest for Untreated patients (1.6 months; log-rank P < 0.0001). After adjusting for age, sex, race, MDS, PPIs, comorbidity score, marital status, income, education, geographic region, and year of diagnosis in the survival model, receipt of all types of antileukemic therapy showed a significant mortality risk reduction compared with palliative care or no treatment. The largest reduction in mortality risk was noted in the Intensive therapy group (hazard ratio [HR] 0.32; 95% CI 0.25-0.40), followed by HMA (HR 0.47; 95% CI 0.43-0.52), Other (HR 0.49; 95% CI 0.43-0.56), and Unknown (HR 0.66; 95% CI 0.62-0.70) compared with the Untreated group.
Conclusions: There was a significant survival benefit for patients who received all types of antileukemic therapy, even among the HMA and Other therapy groups who had similar characteristics to the Untreated group of patients. The findings from this study provide a rationale to strongly consider therapy rather than best supportive care in older patients who do not fit the criteria for more intensive regimens.
Satram-Hoang:Celgene Corp.: Research Funding; Genentech: Research Funding. Parisi:Celgene Corp.: Employment, Equity Ownership.
