Hypomethylating agent therapy use and survival in older patients with chronic myelomonocytic leukemia in the United States: A large population-based study

Abstract

Background: Despite the approval of azacitidine in 2004 and the approval of decitabine in 2006 in the United States for chronic myelomonocytic leukemia (CMML), the overall survival (OS) benefit with hypomethylating agent (HMA) therapy is unclear.

Methods: Older adults (age ≥ 66 years) who had been diagnosed with CMML from 2001 to 2011 were selected from the Surveillance, Epidemiology, and End Results-Medicare database, and propensity score matching was used to match patients who had been diagnosed after HMA approval (2007-2011) and had received HMA treatment with patients diagnosed before HMA approval (2001-2003). Cox proportional hazards models with the matched sample were used to assess the change in OS. A second matched cohort of patients who did not receive HMA after approval and patients diagnosed before HMA approval was used to evaluate survival change attributable to other potential differences between the 2 time periods, such as improved supportive care.

Results: Among 1378 older adults diagnosed with CMML, the median OS was 13 months, and 18.8% received HMAs. In the primary matched analysis, with 225 HMA users diagnosed in 2007-2011 and 395 patients diagnosed in 2001-2003, the median OS times were 17 and 11 months, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.58-0.91; P = .005). In a secondary analysis, the risk of death did not differ between 395 propensity score-matched HMA nonusers diagnosed in 2007-2011 and 484 patients diagnosed in 2001-2003 (hazard ratio, 1.09; 95% CI, 0.91-1.32; P = .34).

Conclusions: Despite limited evidence, HMAs are commonly used to treat older CMML patients. The use of HMAs was associated with a 28% reduction in the risk of death in adjusted analyses. Improvements in supportive care do not appear to account for temporal improvements in OS. Cancer 2017;123:3754-3762. © 2017 American Cancer Society.

Keywords: Epidemiology; Medicare; Surveillance; and End Results (SEER); azacitidine; chronic myelomonocytic leukemia (CMML); decitabine; effectiveness; hypomethylating agents; survival.

Figure 1.. Study sample selection.

CMML, Chronic Myelomonocytic Leukemia; MDS, Myelodysplastic syndromes; AB, Medicare Parts A and Part B; HMO, Health Maintenance Organization.

Figure 2.. Propensity scoring matching methodology.

HMA, Hypomethylating agents; PS, Propensity Score; PH, Proportional Hazards.

Figure 3.. Proportion of patients with CMML who received a HMA by year of diagnosis.

CMML, Chronic Myelomonocytic Leukemia; HMA, Hypomethylating agents.

Figure 4.. Kaplan Meier survival estimates for HMA Users (N=213) stratified by Azacitidine Only (N=119) and Decitabine Only (N=94).

HMA, Hypomethylating agents. Number at risk at 48 months not reported to meet data use requirements (Number decreased from 36 months to 48 months <11)

Figure 5A.. Kaplan Meier survival estimates for Primary Propensity Score matched cohort (N=620) stratified by HMA User (N=225) and Pre-HMA (N=395).

HMA, Hypomethylating agents.

Figure 5B.. Kaplan Meier survival estimates for Secondary Propensity Score matched cohort (N=879) stratified by Non-HMA User after 2006 (N=395) and Pre-HMA (N=484).

HMA, Hypomethylating agents.