Clinical analysis regarding the therapeutic effect of hypomethylating agent in MDS

Abstract

Purpose To analyses clinical impacts of hypomehthylating agents in MDS and to evaluate predictive prognostic factors for response and survival in MDS treated with hypomethylating agents.Patients and Methods Ninety four patients (median age 66 years, range 25~88 years) treated with hypomethylating agents at least 4 cycles were enrolled. Hypomehtylating agents consisted of Azacitidine (AZA, 75mg/m2/day, SQ, for 7days every 4 weeks) and Decitabine (20mg/m2/day, IV, for 5days every 4weeks). Results Median best cycle was 4 (range 1~14 cycles). Overall response rates (ORR) was 67.7% and in subgroup analysis, AZA and Decitabine group was each 70.4%, 69.5%, Higher risk and Lower risk group of IPSS was 70.4%, 69.5%. There were no statistical significances among them. Early achievement of Hematologic improvement (HI, HI on 2nd cycle) was associated with maintenance of HI (P<0.001) and independently predicted better response (Odds ratio (OR)=6.3; 95% CI 1.0~37.0, P= 0.041). Median overall survival (OS) was 15. 4 months (range 3.6~65 months). In multivariate analysis, RAEB-1, RAEB-2 of WHO classification (RAEB-1: Hazard Ratio (HR)=20.1 95% CI 3.8~106.1 ; P<0.001, RAEB-2: HR=19.5 95% CI 2.7~138.7 ; P=0.003 ), Higher risk of IPSS (HR=0.2 95% CI 0.1~9.1) ; P=0.044), presence of complex karyotype (HR=10.3 95% CI 1.1~99.5 ; P=0.044) independently predict poorer OS. RAEB-1 of WHO classification (RAEB-1: HR=4.2 95% CI 1.6~10.9 ; P=0.004) also independently made a role as a predictive factor for poorer progression free survival (PFS).Conclusion In clinical real setting, I found that early achievement of HI independently predict better response and might be a factor for continuation of hypomethylating agents. Complex karyotype, IPSS risk was significantly associated with OS and RAEB-1, RAEB-2 of WHO classification independently predict both worse OS and PFS.