Efficacy of the hypomethylating agents as frontline, salvage, or maintenance therapy among older adults with acute myeloid leukemia (AML).

Abstract

e18002 Background: The hypomethylating agents, azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with AML. Little is known about how AML responds to hypomethylating agents after standard therapy and the use of these agents in the treatment of AML is currently evolving. Methods: We retrospectively examined 76 consecutive AML patients ≥60 years old treated with hypomethylating agents at Wake Forest from 2002-2009 as either 1st-line therapy (n=35), salvage (n=28) or consolidation (n=13). We collected data on age, gender, race, Charleston Comorbidity index (CCI), cytogenetics, type of treatment, Complete Remission (CR), Complete Remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and cox proportional hazards models. Results: In the front line setting 11.4% of patients received azacitidine (AZA), 34.3% received 5 days of decitabine (5DD) and 54.3% received 10 days (10DD). In the salvage cohort 3.6% received AZA, 42.8% received 5DD and 53.6% received 10DD. In the consolidation cohort 18.2% received AZA and 81.8% received 5DD. Response rates (CR+CRi) were reduced in the salvage cohort compared to frontline (3.6% versus 25.7%, p=0.033). Despite the reduced response rate, overall survival in the two cohorts was similar when survival was calculated from time of hypomethylating agent (8.2 [CI 4.8-10.3] vs. 3.1 [CI 1.9-12.0] months, p = 0.2967). In the salvage cohort overall survival from the time of relapse was similar to the overall survival of those treated in 1st consolidation (18.3 [CI 15.1 -23.5] vs. 13.7 [CI 8.0 – 21.6] months, p= 0.3346). This suggests that hypomethylating agents given in first remission did not improve survival over patients who received them only after relapse. Comorbidity burden (by the CCI) showed a non-significant trend with prognosis (p= 0.0667). Conclusions: These data suggest prior cytotoxic therapy decreases marrow response rates to hypomethylating agents but not survival. Furthermore, use of hypomethylating agents for consolidation did not result in an increase in median overall survival when compared to their use in salvage.