Amonafide + ara-C in secondary acute myeloid leukemia (sAML): Consistent efficacy in poor risk populations.

7027 Background: The poor prognosis for sAML (prior MDS or leukemogenic therapy, i.e., tAML) relates to disease (unfavorable cytogenetics and multidrug resistance (MDR) phenotype) and patient (pt) characteristics (elderly w/comorbid illnesses). Amonafide (Xanafide), a topoisomerase II inhibitor, is not a substrate or inhibitor of the MDR efflux pump, P-glycoprotein (Pgp) (Chau 2007 Leuk Res in press; O'Loughlin 2007 Blood 110:702a; Lundberg 2008 ASCO, submitted). A 42% CR rate in this Phase 2 trial was previously reported (Erba 2007 Proc Am Soc Clin Onc 25:373s). We report updated results & long-term follow up.,sAML pts received amonafide 600 mg/m days 1-5 + ara-C 200 mg/m CIV days 1-7. A 2 course could be given for persistent leukemia on day 14. CR pts received either stem cell transplant or intermediate/high dose ara-C depending on age. Centralized pathology review and DSMB were utilized. Primary endpoint was complete remission (CR) with or without (CRi) hematologic recovery. Median duration of follow-up is 208 days.,Enrollment 88 pts; median age 63 yrs (range 23-87); prior MDS, 45.5%; tAML 54.5%; unfavorable cytogenetics, 47%. Overall CR was 42%, 34 CR + 3 CRp (CR without recovery of platelets). CR rate was consistent across poor risk subgroups: age <60yrs, 39.4%; >60yrs, 43.6%. MDS → AML without and with prior therapy for MDS (mostly azacytidine), 43.5% & 36%; tAML, 40%; intermediate & unfavorable cytogenetics, 60% & 22%. 6 of 10 CR pts with informative cytogenetics achieved cytogenetic CR. 30 pts received post-remission therapy with ara-C (21), BMT (7), or both (2). Median duration of CR is >10 months, among age > 60 is > 9 months, with pts continuing on study. Kaplan-Meier estimate of continuous CR at 12 months is 43%, 47%, 64% and 57% for all pts, older pts (>60), pts with tAML, and pts with poor risk cytogenetics. Median overall survival (OS) is 7 months, and median OS for CR pts is >11 months. Safety profile was acceptable, death within 28 days was 20.5%.,This study demonstrated robust and durable CR across poor-risk subsets of sAML, including older pts, tAML, and previously treated MDS → AML. Amonafide and ara-C may be a promising alternative for pts with sAML, especially those with over- expression of Pgp. This is being tested in a Phase 3 clinical trial. [Table: see text].