ALBERT

Description: Abstract 843 Background: AZA prolongs survival in higher-risk MDS including patients (pts) with 20-29 % marrow blasts, now considered WHO-AML ( Lancet Onc, 2009). However, no large AML cohorts (especially with '30% marrow blasts) treated upfront with AZA have been reported. Methods: An AZA compassionate program (ATU) was initiated in France in Dec 2004 for higher risk MDS, and AML considered not candidates or refractory to intensive chemotherapy (IC). We retrospectively analyzed WHO AML pts having received at least 1 cycle of AZA in the 42 centers with complete pt reporting, excluding those previously treated by IC, allo SCT, low dose AraC or a hypomethylating agent. Results: 138 pts were included between Dec 2004 and Dec 2008; M/F: 86/52; median age 73 years (y) (range 31-87), 117 pts (85%) were 〉 65 y and 54 (40%) 〉75y. 65 pts (47%) had prior WHO MDS and 30 pts (22%) therapy related (tAML). 44 pts (32%) had 20-29% marrow blasts. Median WBC was 3.0 G/L [0.8-111.5]. Karyotype (MRC classification), was intermediate (int) in 60 pts,( including 38 normal (NK), and 7 isolated +8 ) adverse in 67 pts (including 42 -7/ del7q, 41 del5q/-5, 45 complex karyotype, two 3q26) and failed in 11 pts. With a median follow-up of 11.3 months, pts received a median of 4.5 AZA cycles (range 1-26). Treatment was according to FDA-EMEA approved schedule for MDS in 95 pts (69%) and a less intensive schedule (5d/4w, or 10 G/L (32 pts in our cohort) carried poorer prognosis ( 1 y OS of 27% vs 44% ,p=0.01); NK had better OS (1-y OS: 66%) than adverse cytogenetics (1-y OS: 30%, p=0.01) but also other “intermediate-risk” abnormalities (1-y OS: 30%, p=0.03). Marrow blast % did not influence OS and survival, whatever the cut off chosen. In particular, pts with 20-29 % marrow blasts had 22% AML response and 1 y OS of 50%, compared to 21% and 1 y OS of 35%, respectively, in pts with 〉30% marrow blasts (p=NS and NS, respectively). Prior MDS also had no influence on survival. Overall, 33 pts required hospitalization during treatment, mainly for neutropenic fever. A landmark analysis at the time of evaluation showed that achievement of CR, CRi or PR was associated with improved OS (1y-OS 55% vs 31%,p=0.007). In pts with no AML-IWG response, however, achievement of HI also predicted better survival: 1 y-OS 55% vs 19 %, p=0.02. In the 54 pts older than 75 y (ie pts generally considered unfit for IC), 12 (22%) had AML response including CR in 9 (17%) and 3 PR (5%). 1y-OS was 41 % vs 38% for younger pts (p=NS). Hospitalisation was needed in 31% of them vs 32% in younger pts (p=NS). Conclusion: In this untreated cohort of generally older AML pts considered non candidates for intensive chemotherapy, response rate was 21% and 1 y OS 40%. Higher WBC counts and adverse karyotype were associated with poorer OS, but marrow blast %, whatever the threshold chosen, had no influence on outcome. Age above 75 y was associated with similar response and 1y OS. Finally, pts without AML IWG responses but with improved cytopenias also appeared to have improved survival. Disclosures: Off Label Use: Azacytidine is approved by FDA and EMEA in the treatment of high risk MDS and AML up to 30% of bone marrow blast.. Fenaux:CELGENE: Research Funding; AMGEN: Research Funding.

Description: Abstract 1773 Poster Board I-799 Background Patients aged ≥ 80 years account for as many as 30 to 35% of MDS in large registries (Rollison Blood 2008; Germing Ann Hematol 2008). Those patients (pts), when they have high risk MDS, are rarely candidates for chemotherapy (CT), even at low dose like low-dose araC, due to the risk of myelosuppression, and generally receive best supportive care (BSC) only, with very poor survival. Azacytidine (AZA) improves survival in higher-risk MDS pts, including RAEB-t and in pts aged 〉 75, with more limited myelosuppression than CT (Lancet Oncol 2009). Methods An AZA compassionate program (ATU) was opened in France between Dec 2004 and Dec 2008 for higher risk MDS, and for AML not candidates or refractory to intensive chemotherapy (IC). We retrospectively analyzed the outcome of MDS (including RAEB-t and CMML) pts ≥ 80 years from the 42 centers with complete patient (pt) reporting, and having received ≥ 1 cycle of AZA. Results The study population included 41 pts (M/F: 22/19; median age 83y, range 80-91) WHO diagnosis was RMCD in 2, RAEB-1 in 12, RAEB-2 in 16, and RAEB-t in 8, CMML in 3; IPSS cytogenetic risk favorable (fav) in 16, intermediate (int) in 10, and unfavorable (unfav) in 9 (karyotype failure/not done in 6); IPSS was int-1 in 8, int-2 in 18 and high in 13, undetermined in 2. Six pts had previously been treated unsuccessfully with low-dose AraC. With a median follow-up of 12 months, pts had received a median of 4 cycles (1-12) of AZA, at FDA/EMEA-approved schedule (75 mg/m2/d x7d/4 w) in 54% or a less intensive schedule (5d/4w, or

Description: Abstract 1054 Poster Board I-76 Background: Limited options are available in AML refractory to or relapsing after intensive chemotherapy (IC), especially in elderly patients (pts). Azacytidine (AZA) prolongs survival when used as first line treatment of higher-risk MDS and WHO AML with 20-29% BM blasts (Lancet Oncol 2009). Its role in relapsed/refractory AML, especially with baseline BM blasts 〉 30%, has not been evaluated in large patient (pt) series. Methods: An AZA compassionate program (ATU) was opened in France between Dec 2004 and Dec 2008 for higher risk MDS, and for AML not candidates or refractory to IC. We retrospectively analyzed the outcome of WHO AML (including RAEB-t) included in this program in the 42 centers with complete pt reporting, and who had received ≥ 1 cycle of AZA after relapse or failure of IC. Results: 184 pts were included. Median age was 64 years, 58 pts had prior MDS, 14 had RAEBt at diagnosis, and 16 had therapy-related AML. Cytogenetics (MRC classification) was favorable (fav) in 2, intermediate (int) in 115 (including normal karyotype (NK) in 75), unfavorable (unfav) in 53, and failed in 14 pts. 65 pts had failed to achieve CR (51 after 1, and 14 after ≥2 courses of induction IC), 91 pts were in 1st relapse (median CR duration: 11 months), 28 were in 2nd or subsequent relapse. 20 pts previously had received alloSCT (14 in 1st CR, 5 in 2d CR, 1 refractory). Median follow-up was 15 months. The median number of AZA cycles was 3 (1-28) at FDA/EMEA-approved MDS schedule (75 mg/m2/d x7d/4 w) in 75% and less intensive (5d/4w, or

Description: Abstract 3820 Poster Board III-756 Background AZA provides 50-60% responses and improves OS in higher-risk MDS (Lancet Oncol 2009) but prognostic factors of response and OS remain largely unknown. Methods An AZA compassionate program (ATU) was opened in France between Dec 2004 and Dec 2008 for higher risk MDS, and for AML not candidates or refractory to intensive chemotherapy (IC). We retrospectively analyzed the outcome of higher risk MDS (including RAEB-t) patients (pts) included in this program in the 42 centers with complete patient (pt) reporting, having received ≥ 1 cycle of AZA, and excluding those who had received prior allo SCT, IC, or a hypomethylating agent. Results 233 pts (M/F: 145/88) with a median age of 71y (range 20-91) were included. Diagnosis (WHO classification) was: RA±RS: 2, RCMD±RS: 7, RAEB-1: 48, RAEB-2: 123, and RAEB-t: 53; IPSS cytogenetic risk was favorable (fav) in 75 (32%), int (intermediate) in 35 (15%), and unfavorable (unfav) in 112 (48%) (failure in 11, 5%); IPSS was: int-2 in 133 (57%), high in 97 (42%), NA in 3 (1%). Median time since diagnosis was 5 months (range 0–209). 29 patients (12%) had previously received low dose Arac (LD AraC). 162 pts (70%) were RBC transfusion dependent, including 49% requiring ≥ 4 RBC units/8 weeks. Median follow-up was 13 months. Patients received a median of 5 cycles (range 1-26) of AZA, at FDA/EMEA-approved schedule (75 mg/m2/d x7d /4 week) in 70% patients and a less intensive schedule (5d/4w, or 50% decrease; n=47; p=NS), while reaching HI-P had a borderline favorable effect on OS (n=51, p=0.07). Conclusion No pre-treatment parameter (apart from prior LD-AraC treatment) predicted response to AZA. Regarding OS, presence of PB blasts, intermediate or unfavorable cytogenetics and transfusion dependency were associated with poorer survival. Improvement of anemia (and to a lesser extent of platelets) rather than BM blast reduction were associated with survival improvement. Whether other tests, including methylation profiles, may provide further information predicting response to AZA is being evaluated. Disclosures: Fenaux: Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Ortho Biotech: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.