E. Laille,1 Z. Xiao,2 X. Du,3 Q. Dong,1 S. Songer,1 C. Beach1; 1Celgene Corporation, Summit, NJ, 2Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China, 3Guangdong General Hospital, Guangzhou, China

BACKGROUND: PK-related gene polymorphisms vary among populations. Steady-state PK profiles of AZA in subjects with HR-MDS in China, and in a historical cohort of mainly Caucasian North American (NA) subjects with hematologic malignancies, were compared.
METHODS: Chinese HR-MDS subjects (IPSS Int-2 or High risk) received SC AZA 75 mg/m2/d x 7 days.
RESULTS: AZA PK parameters in 12 Chinese subjects (67% male, mean age 53±11 yrs) were compared with those in 45 NA subjects (80% male, 69±11 yrs; MDS n=30, AML n=11, CMML n=4). AZA was rapidly absorbed in Chinese (median Tmax 0.25 hr) and NA (0.50 hr) subjects. PK profiles in both cohorts were similar in shape, except Cmax was higher in Chinese subjects. Following Cmax, mean AZA concentrations declined in a multiphasic manner in both cohorts. All other PK parameters for Chinese subjects were within range of those for NA subjects (Figure). No drug accumulation following multiple-dose administration and high inter-subject variability were observed in both cohorts. AZA 7-day dosing was generally well tolerated in Chinese subjects.
CONCLUSION: No meaningful differences in PK of SC AZA between Chinese and NA subjects were evident. Differences in Cmax did not alter the safety profile in Chinese subjects. These data suggest no initial SC AZA dose adjustment is necessary for Chinese patients with HR-MDS.