Survival Benefit with Decitabine Compared to Historical Experience with Intensive Chemotherapy in Patients with Higher Risk Myelodysplastic Syndrome (MDS).
Authors: Jabbour Elias , Kantarjian Hagop M. , Cortes Jorge , Wierda William G. , Ferrajoli Alessandra , Faderl Stefan , O’Brien Susan , Ravandi-Kashani Farhad , Verstovsek Srdan , Garcia-Manero Guillermo , Davisson Jan , Giles Francis , Shan Jianqin , Issa Jean-Pierre 
Published: October 2019

Abstract
Background
Decitabine is a hypomethylating agent, approved by the FDA for treating MDS. Intensive chemotherapy is one treatment option in higher risk MDS. The comparative efficacy of these two strategies, decitabine vs. intensive chemotherapy, has not been evaluated.
Study Aims
Compare the results of decitabine in MDS with contemporary historical experience with intensive chemotherapy (as used in AML) in patients with higher risk MDS.
Study Group and Treatment
The study group treated with decitabine included 115 patients with higher risk MDS treated on our decitabine frontline study. (Kantarjian, Blood 2006; First Edition Online). The contemporary historical experience included two cohorts:
Group A: 115 patients receiving intensive chemotherapy from 1995–2005 and matched for age, IPSS and cytogenetics; and Group B: All 376 patients treated with intensive chemotherapy from 1995–2005 with similar entry criteria as the decitabine study.
Patients received decitabine 20 mg/m2 IV/D x 5 every four weeks. Response was evaluated by the modified IWG criteria (Cheson, Blood 108:419, 2006) In comparing decitabine to Group B, a multivariate analysis was conducted to assess the independent effect of decitabine vs. intensive chemotherapy.
Results
115 patients were treated with decitabine; median age 64 years (range 37–89 years). IPSS risk groups: intermediate-1 17%, intermediate-2 30%, high 15%, not assessable 39%. Decitabine was given for a median of 7 courses (range 1 to 23); number of decitabine courses 3 or more in 81/89 patients (91%) followed on study for at least 6 months. Hemoglobin <10 g/dL in 76%; thrombocytopenia <100 x 109/L in 72%; ANC <1.0 x 109/L in 47%; chromosomal abnormalities in 63%; prior therapy for MDS in 54%; marrow blast 5% or more in 79%. Overall, 80 patients (70%) achieved IWG response: CR 40 (35%), PR 2 (2%), marrow CR +/− other hematologic improvements (HI) 26 (23%), other HI 12 (10%). Median remission duration was 20 months; median survival was 21 months. The CR rates by AML criteria (Cheson JCO21:4642, 2003) were 43% with decitabine and 46% with intensive chemotherapy in Group A, and 52% with intensive chemotherapy in Group B. Mortality at 6 weeks was 3% with decitabine vs. 12% with intensive chemotherapy (p=0.002); the 3-month mortality was 7% with decitabine vs. 22% with intensive chemotherapy. The survival was better with decitabine versus intensive chemotherapy in Group A (median 22 month vs. 11 month; estimated 2-year survival rate 47% vs. 25%, p<0.001). A multivariate analysis for survival in all 491 patients receiving decitabine or intensive chemotherapy (Group B) identified the following to be independent adverse factors for survival: abnormal cytogenetics, older age, anemia, thrombocytopenia, and poor performance status. Entering decitabine vs. intensive chemotherapy after accounting for the effect of other prognostic factors selected decitabine as an independent favorable prognostic factor for survival (pvalue 0.002; hazard risk 0.76).
Conclusions
Compared with intensive chemotherapy decitabine is associated with a survival benefit in higher risk MDS.