title: Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML).
abstract: The hypomethylating agents (HAs), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with acute myeloid leukemia (AML). Little is known about how AML responds to hypomethylating agents after standard therapy, and the activity of these agents in a real-world setting is not well studied. We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002 to 2011 treated with HAs either as first-line (n = 34), salvage (n = 28), or consolidation (n = 13) therapy. We collected data on age, gender, race, Charlson 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. Frontline response rate (CR + CRi) was 26.5 %, and median overall survival (OS) was 3.4 months (95 % CI 1.3-7.4), with 18 % alive at 1 year. In the salvage cohort, the response rate was significantly lower compared to frontline (3.6 versus 26.5 %, p = 0.017). Despite the reduced response, OS from time of HA treatment was longer than frontline at 8.2 months (CI 4.8-10.3). In the consolidation cohort, OS was 13.8 months (CI 8.0-21.6) with one patient in remission more than 30 months from diagnosis. These data suggest that prior cytotoxic therapy decreases marrow response rates to HAs but not survival. Furthermore, use of hypomethylating agents for consolidation resulted in a median overall survival over 1 year in a cohort of older patients. This suggests that hypomethylating agents have activity in all phases of AML treatment.
authors.affiliation: Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Tawfik
authors.forename: Sarunas
authors.initials: S
authors.lastname: Sliesoraitis
authors.forename: Susan
authors.initials: S
authors.lastname: Lyerly
authors.forename: Heidi D
authors.initials: HD
authors.lastname: Klepin
authors.forename: Julia
authors.initials: J
authors.lastname: Lawrence
authors.forename: Scott
authors.initials: S
authors.lastname: Isom
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Ellis
authors.forename: Megan
authors.initials: M
authors.lastname: Manuel
authors.forename: Sarah
authors.initials: S
authors.lastname: Dralle
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Berenzon
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Timothy
authors.initials: T
authors.lastname: Pardee
mesh_terms: D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015897:Comorbidity; D060830:Consolidation Chemotherapy; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D004249:DNA Damage; D019175:DNA Methylation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects; D000077209:Decitabine; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D000077209:Decitabine; D004248:DNA (Cytosine-5-)-Methyltransferases; D001374:Azacitidine