Hypomethylating Agent Therapy for Acute Myelogenous Leukemia (AML) Can Induce Sustained Responses with Low Induction Mortality.

Hypomethylating agents (HMAs) are effective in inducing remission in myelodysplastic syndrome (MDS). Limited data suggests that these agents are effective in the therapy of patients with AML. A single center retrospective analysis was done to assess the response to HMAs (azacitidine or decitabine) in patients with AML in our institution.

We retrospectively reviewed all AML patients treated with either azacitidine (AZA) or decitabine (DAC) from 1/1/05 to 7/1/09. Responses were defined according to the 2003 International Working Group criteria into complete remission (CR), partial response (PR) and no response (NR). In addition some patients achieved a hematological improvement (HI) according to the modified IWG criteria for response in MDS without satisfying any of the AML response criteria. We also describe those patients as they did have clinical benefit. The overall survival (OS) was determined using the Kaplan Meier method. Patients were censored at the time of stem cell transplantation (SCT). Of the 24 patients identified, 11 were female, and 12 had not received previous treatment. All 12 previously untreated patients either refused or could not tolerate induction chemotherapy. The median age of all patients was 69. The median follow up time from start of the HMA was 196 days. 5 patients were treated with AZA, 13 with DAC and 5 patients received treatment with both HMAs sequentially. Of the 5 pts who underwent SCT, 1 received the HMA after SCT for relapse, and 4 had the SCT after induction treatment with HMAs. Of those 4 pts, 2 were previously untreated and all 4 patients achieved CR prior to SCT. The cytogenetic risk categories were good (2 patients), intermediate (10 patients) and poor risk (10 patients). The median and range for WBC, hemoglobin and platelets at the time of diagnosis was: 5 × 10⁹/L (0-850), 7 gm/dl (5-12) and 77 × 10⁹/L (13-357) respectively. Of the 21 patients evaluable for response, 7 (33%) achieved CR, 1 (4%) CRp (CR without platelet recovery), and 2 (9.4%) HI. The median number of cycles was 3.5 (range 1-23). Of the 8 patients who achieved CR/CRp, 4 had poor risk cytogenetics and 4 were previously untreated. One patient with inversion 16 was refractory to 2 chemotherapy regimens and achieved CR with DAC. The median overall survival (OS) was 366 days, 542 and 366 days for the whole group, previously treated and previously untreated patients respectively. None of the patients died from treatment related complications. The median OS was not reached for patients achieving a CR (range 206 days to 769 days) and was 149 days (range 43-664) for patients with no response. Of the 5 pts who received both HMAs, one patient achieved CR with the second agent.

Hypomethylating agents are active in newly diagnosed and refractory AML with no treatment related mortality in our institution. The results compare well with other regimens in the treatment of relapsed/refractory AML (25% response rate). Some patients may benefit despite not achieving the IWG defined response criteria. Randomized studies comparing hypomethylating agents to standard therapy in patients with AML will be open soon.

Bredeson:Esai: Honoraria. Atallah:Celgene: Honoraria.