Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemia: Commercially available Therapy, excluding Transplantation: Poster III
Patients and Methods: From 2009 to 2014 we treated 75 consecutive patients with newly diagnosed high-risk MDS or de novo AML, with AZA (75mg/m2 sc. d1-7, qd29). Patients who responded to AZA after at least four courses and had a subsequent relapse, as defined by worsening of peripheral blood counts, increase of blasts or increase in transfusion frequency, received a second-line treatment with subcutaneous LDARAC (2x 10 mg/m2/d sc., d1-10, qd29) until progression or were followed by best supportive care, including symptomatic treatment, transfusions or treatment of clinical infections- but without chemotherapy.
Results: After first-line AZA 48/75 (64%) achieved a partial hematologic response (n=23), stable disease (n=14) or clinical benefit (n=7). The median overall survival (OS) of all 48 patients with response or clinical benefit to AZA was 27 months. Median duration of response was 13 (4-56) months. Cytogenetic risk at diagnosis was a significant prognostic factor for OS (P<0.001), but not age or ECOG-PS (P=0.17 and P=0.68, respectively). After a median follow-up of 24 months, 31 patients had a loss of hematologic response. Fifteen of 31 relapsed patients were treated with a second-line therapy with LDARAC until progression. Two of those 15 patients received an initial re-induction therapy with intermediate dose cytarabine plus daunorubicine ("5+2"). 16 patients were followed by BSC. Four of 15 patients who were treated with LDARAC achieved a partial hematologic response and 6/15 had stable disease with a median response duration of 4 months. In the BSC group no objective responses were observed. The median overall survival from the time of progression on AZA (OS-2) was 7.2 months in patients treated with LDARAC versus 2.9 months in patients who received BSC care only (P<0.01). In a multivariate analysis response to LDARAC was the only significant prognostic factor for OS-2 (P=0.02, HR: 3.16), while age, ECOG-PS or cytogenetic risk did not reach statistical significance.
Conclusions: Our analysis shows that second-line treatment with LDARAC may add a survival benefit of approximately 3 months compared to BSC alone. The second overall survival (OS-2) of 7.2 months is within the range achieved with LDARAC as primary treatment for this patient population. Our data indicate that LDARAC can be considered as a reasonable therapeutic option after failure of first-line treatment with demethylating agents like AZA. This clinical observation is supported by recent pre-clinical data, showing that epigenetic modifications in AML cells can have a sensitizing effect for the subsequent administration of cytarabine.
Disclosures: No relevant conflicts of interest to declare.
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