Low-Dose Decitabine (DAC), Alone or in Combination with All-Trans Retinoic Acid (ATRA), Is An Active First-Line Treatment in Older AML Patients of All Cytogenetic Risk Groups: Final Results of the FR00331 Multicenter Phase II Study.

Abstract 4141 Medically non-fit AML patients (pts), often with adverse cytogenetics, have few therapeutic options. We performed a large phase II trial in untreated AML pts >60 years ineligible for induction. Primary endpoint was best response: complete (CR) or partial remission (PR) or an antileukemic effect (ALE, >25% bone marrow [BM] blast reduction). Secondary endpoints: overall survival (OS) and safety. DAC was given at 15 mg/m 2 q8 hours on day 1-3, total 135 mg/m 2 , q6 weeks for up to 4 cycles, with ATRA (45 mg/m 2 /day p.o. for 28 days in cycle 2) to be administered to pts not attaining a CR or PR after course 1, i.e. those with ALE or stable disease (SD). Maintenance with 20 mg/m 2 DAC i.v. over 1 hour on 3 days (total 60mg/m 2 , outpatient administration) q 6-8 weeks was offered to pts completing all 4 cycles. 227 pts were recruited (median age 72 yrs, range 56-86). 38% of pts were ≥75 yrs of age, 23% had a performance status of ECOG > 2, and by comorbidity scoring (HCT-CI) 80% of pts had at least one, and 36% had three or mor comorbidities. Adverse cytogenetics or preceding MDS were present in 34% and 54%, respectively. Median WBC before treatment was 4400/μl (range, 500-241 000, >50 000/μl in 10%). Median BM blasts were 55% (10-100). A median of 2 DAC cycles was given (range 1-4). 100 pts received ATRA during course 2, and 51 pts (out of 79 who completed 4 cycles) received a total of 306 DAC maintenance cycles (median 5, range 1-19). Best response was CR in 30 pts (13%) and PR in 29 pts (13%). An ALE occurred in 60 pts (26%), resulting in a 52% overall response rate. SD was seen in 57 pts (25%), 19 pts (8%) had progressive disease, 29 (13%) had early death and 3 pts (1%) were inevaluable for response. Median OS from start of treatment was 5.5 months (range, 0-57.5+), the 1-year survival 28% (95%CI: 22%,34%). Pts with adverse cytogenetics did not differ from those with non-adverse cytogenetics in CR+PR rate nor in median OS. The addition of ATRA to DAC during cycle 2 resulted in similar survival (from start of cycle 2) despite the initial modest response to DAC of these 100 pts. Toxicities of DAC (alone or in combination with ATRA) were predominantly hematologic, no differentiation syndrome was observed. Conclusions: DAC is very well tolerated by older, medically non-fit AML pts, with myelosuppression being the major toxicity. CR+PR was attained by 26% of pts. A frequent ALE and the good feasibility of outpatient maintenance support continued DAC treatment, and the response to DAC combined with ATRA warrants a randomized study. Disclosures: Off Label Use: Decitabine (FDA approved for MDS and AML with up to 30% bone marrow blasts) is used here (at the approved dose and schedule)in AML patients with >30% blasts. ATRA (approved for APL) is used here in non M3 AML patients.