Phase II trial of the combination of subcutaneous bortezomib (Bortez) and pegylated liposomal doxorubicin (PLD) for the treatment of patients with acute myelogenous leukemia (AML).

7081 Background: The proteasome inhibitor Bortez has activity in AML, both as a single agent and in combination with standard induction. Bortez inhibits NF-κB signaling, and NF-κB activity promotes anthracycline resistance. The combination of Bortez and PLD was well tolerated in trials for multiple myeloma. Methods: We performed a phase II trial of Bortez and PLD in subjects at least 18 years old with relapsed/refractory AML or treatment naive AML unfit for or who refused standard therapy. Bortez 1.5mg/m2 was given subcutaneously on days 1, 4, 8, and 11, and PLD 40mg/m2was given IV on day 4. Cycles were 21 days long. The primary endpoint was objective response rate (ORR), defined as complete remission (CR) plus partial remission (PR). Results: Fifteen subjects (53% male) were enrolled. Median age was 70 years (range 32-83). Four had relapsed, five had refractory, and six had untreated AML. Subjects had a median of two prior lines of therapy (range 0-7), including two with prior allogeneic transplantation....