Abstract 1054

Poster Board I-76


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.


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.


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 <75 mg/m2/d) in 25% pts, with concomitant valproic acid (VPA) in 33%.

Febrile neutropenia occurred in 67% pts, requiring hospitalization in 41%. Overall response rate (ORR) (Cheson et al. JCO 2003 criteria) was 11%: CR: 13 (7%), CRi: 5 (3%), PR: 1 (1%). 44 pts died before completing 4 cycles, and AZA was stopped before 4 cycles in another 52 pts (lack of response: n=43, severe infection: n=3, pt decision: n=5, allo SCT: n=1). The remaining 69 pts failed to achieve response after 4 cycles. In the 13 pts with CR, 6 (43%) were in persistent CR after a median follow-up of 7 months. In total, 9 pts received alloSCT after AZA: 2 CR, 7 refractory. Median OS was 7.8 months (1y OS: 29.1%). In univariate analysis, age, prior MDS, disease status (1st, ≥2nd relapse, refractory), WBC count at diagnosis, addition of VPA, and CR1 duration for pts in 1st relapse, did not influence ORR or OS. Only normal karyotype at onset of AZA improved ORR and OS (ORR: 18% vs 7%, p=0.04; 1y-OS: 44.4% vs 15.9%, p=0.001).

We next restricted our analysis to the 141 pts with refractory AML (defined as failure of ≥2 IC cycles in pts <60y and ≥1 IC cycle in pts ≥60y) or in first relapse. 102 of them were aged ≥ 60y (median age 68y; 40 refractory, 62 in 1st relapse; median 1st CR duration: 12 months, range 2 - 54). Their ORR was 13% (CR 9%, CRi 4%). 1y OS was 29.4%, and median OS 8.9 months. OS was not influenced by previous MDS (n=32) or disease status (relapse/refractory). OS was improved in pts with NK (1y OS 42.5% vs 17.3%, p=0.02).

The remaining 39 pts were aged < 60y (median age 52y); 10 of them were refractory, and 29 in first relapse (including 12 with unfav karyotype and 10 having failed 1 IC cycle after 1st relapse). Only 1 pt obtained CR and 1 PR (ORR: 6%), and median OS was 6.9 months (1y OS: 30%).


In this high-risk population of relapsed/refractory AML, AZA resulted in significant responses and OS in AML pts refractory to one cycle of intensive chemotherapy (IC) or in untreated first relapse after IC, who were generally elderly pts. Results were more limited in pts with refractory disease after 2 induction cycles or first relapse resistant to one cycle of IC (who were generally younger). Those results warrant further studies of AZA in combination to other active agents in this population, particularly in elderly patients.


Off Label Use: Azacytidine (FDA and EMEA approved in higher-risk MDS and RAEBt) used in WHO AML (including with marrow blasts > 30%). Fenaux:AMGEN: Research Funding; CELGENE: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.