Myelodysplastic Syndrome Patients Obtaining a Cytogenetic Response to Outpatient Decitabine Experience Improved Hematological Responses and Longer Survival: Additional Analyses From the ADOPT Trial.

Abstract 3817 Poster Board III-753 Background The multi-center ADOPT trial (J Clin Oncol 2009; 27:3942) demonstrated that decitabine (Dacogen), a cytidine analog with hypomethylating and direct cytotoxic properties, when administered to MDS patients with IPSS '0.5 on an outpatient schedule of 20 mg/m2 IV infusion 5 days per month resulted in an overall improvement rate of 51%, including 32% complete responses (CR+mCR), using the International Working Group 2006 criteria. The impact of obtaining a cytogenetic response to decitabine therapy on subsequent hematological parameters or survival is the focus of this analysis. Study Design/Methods 99 patients with de novo or secondary MDS were enrolled on the ADOPT trial. 49 patients had abnormal cytogenetics at baseline. 33 patients underwent at least one successful post-treatment karyotypic analysis and were therefore evaluable for cytogenetic response. Data analysis utilized student t-tests and comparisons of proportions. Results 17/33 evaluable patients (52%) achieved a cytogenetic response, with 11 complete responses and 6 partial responses (i.e., >50% reduction in abnormal metaphases). Responses were noted among patients in all IPSS cytogenetic risk categories: low risk cytogenetics 3/3 (100%), intermediate risk cytogenetic 5/8 (62%), and high risk cytogenetic (43%). Cytogenetic responses by abnormality included: -Y (3/3), del 5q (1/7) 1, del 20q (1/2), complex (6/14), chromosome 7 abnormalities (6/14), +8 (5/6), and others (3/7). Baseline characteristics were similar among cytogenetic responders and non-responders: mean age 72.2 vs 68.6 years (p=0.30), males 94 vs 63% (p=0.07), secondary MDS 24 vs 13% (p=0.72), high risk IPSS 35 vs 63% (p=0.21), int-2+high risk IPSS 59 vs 85% (p=0.20), blasts <10% 59 vs 31% (p=0.21), red cell transfusion dependent 41 vs 69% (p=0.21) and platelet transfusion dependent 6 vs 19% (p=0.54). The median time to cytogenetic response was 2.3 months, coinciding with the first post-treatment marrow sampling timing. Of the 17 cytogenetic responders, 13 (76%) had a clinical hematological responses (10 CR and 3 mCR) which was significantly higher (p=0.003) than the 3 of 16 evaluable patients (18%) not experiencing a cytogenetic response. Among cytogenetic responders the duration of the hematological response (451 days, 95% CI 143, NE) also was greater than the duration of hematological response among cytogenetic non-responders (219 days, 95% CI 184, NE). 71% (12/17) of cytogenetic responders were red cell transfusion independent on study by IWG criteria compared to 44% (7/16) non-cytogenetic responders (p=0.22). Significantly more cytogenetic responders achieved prolonged red cell transfusion independence lasting at least 24 weeks (10/17; 59%) compared to cytogenetic non-responders (3/16; 19%) (p=0.04). 88% (15/17) of cytogenetic responders were platelet transfusion independent during the study compared to 75% (12/16) non-cytogenetic responders (p=0.61). Higher rates of prolonged platelet transfusion independence lasting at least 24 weeks were achieved among 82% (14/17) cytogenetic responders versus only 38% (6/16) cytogenetic non-responders (p=0.03). Achieving a cytogenetic response correlated with improved survival. Cytogenetic responders had a median survival of 627 days (95% CI 420,760) versus 318 days (95% CI 265, 447) for cytogenetic non-responders. Conclusions Outpatient administration of decitabine (20mg/m2 IV 5 days per month) resulted in cytogenetic responses in 52% of patients with MDS with baseline cytogenetic abnormalities, with a median time to response of 2.3 months. Patients achieving a cytogenetic response had higher rates of hematological responses, longer durations of transfusion independence, and a doubling of projected survival. This analysis suggests that a deeper early response documented by cytogenetics with decitabine correlates with improved long term outcomes, and supports early cytogenetic testing to predict hematological response. Disclosures: Goldberg: Eisai, Inc.: Research Funding.