A phase II study of twice-daily (BID) cytarabine (A) and fludarabine (F) and gentuzumab ozogamycin (GO) in patients (pts) with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

Abstract

6568 Background: High-dose A containing regimens are still considered standard options for pts with AML relapsing after a first Complete Remission (CR) lasting more than 12 months. We conducted a phase II study assessing the efficacy and safety of BID FA-GO. Methods: Pts with Relapsed/Refractory AML, de novo AML unfit for other medical therapies, intermediate-2 and high-risk MDS, and CML-BC, with a PS < 3, as well as normal organ functions were eligible. Pts were scheduled to receive F 15 mg/m2 IV q12 hrs day 1 to 5 as well as A at the dose of 0.5 g/m2 IV over 2 hrs q12 hrs day 1 to 5. GO was administered at the dose of 3 mg/m2 IV on day 1 for the 1st 66 pts enrolled. Courses were repeated every 4 to 6 weeks for a maximum of 7 courses. Pts with CML were allowed to receive concomitant TKIs. Results: 103 evaluable pts were enrolled: 13 (14%) with de novo AML, 10 (10%) with AML in 1st relapse with a duration of 1st CR (CRD1) of ≥12 months, 25 (26%) with AML with CRD1 <12 months, 48 (50%) with AML in 2nd relapse and beyond, 4 (4%) with MDS, and 8 (8%) with CML-BC. Median age was 62 years; 84 pts (88%) had a PS ≥1. Cytogenetic analyses were abnormal in 68 % including chromosomes 5 and 7 abnormalities in 20%. The overall response (OR) rate was 32% including CR in 25 pts (26%) and CRp in 6 (6%). The overall 4-week mortality rate was 9% (Table). With a median follow-up of 16 weeks, the 16-week EFS, OS, and CRD rates were 30%, 59%, and 88%, respectively. When compared to historical match cohort pts treated at our institution, BID FA-GO was better, with an ORR rate of 60 % in pts with AML in first relapse with CRD1 ≥12 months compared to an expected rate of 50%, 28% in pts with relapsed AML with CRD1< 12 months compared to 11%, and 23% in pts with AML beyond the first salvage compared to 7%. The treatment was well tolerated with only 3% of the pts experiencing grade 3 and 4 toxicities including mainly skin rash. Conclusions: BID FA-GO appears to be active with an ORR of 32% in heavily pre-treated population. This combination appears to be safe with a low rate of 4-week-mortality of 9%. Parameter (%) De novo S1 (CRD1 ≥ 12 mos) S1 (CRD1 < 12 mos) ≥ S2 OR 53 60 28 23 CR 38 50 28 17 CRP 15 10 0 6 4-wk mortality 8 0 12 10