Azacytidine (AZA) in MDS (including RAEB-t and CMML) in Patients (pts) ≥ 80 Years: Results of the French ATU Program.

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).

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.

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 <75 mg/m2/d) in 46%. Dose reduction was more frequent than in pts < 80y (30%, p=0.04).

Febrile neutropenia was reported in 36% pts, 67% of whom required hospitalization. Both rates were comparable to those observed in pts < 80 years (p=0.2 and p=0.5, respectively), and were not lower in pts treated by less intensive AZA dosing (p=0.7; and p=0.6 respectively). 5 pts (12%) died before completion of 4 cycles, compared to 10% below the age of 80y (p=0.7).

According to IWG 2006 criteria, the overall response rate (ORR) was 34%, including CR in 6 pts (15%), PR in 2 (5%), marrow CR (mCR) in 3 (7%), stable disease (SD) with HI in 3 (7%), SD without HI in 9 (21%), progression in 12 (29%), and AZA discontinuation before 4 cycles in 6 (16% including 5 deaths, 1 SAE). The ORR did not significantly differ from that of pts < 80y (45% p=0.6).

Median OS was 17.1 months and 1-y and 2-y OS were and 59.7% and 49.8% respectively, not significantly different from OS of pts < 80y (median OS: 15 months, p=0.27). The number of patients was too small to analyze prognostic factors of response to AZA and survival.

Although this cohort of higher risk MDS aged 80 or greater obviously included a selected population of relatively “fit” very old persons, our results suggest that treatment with AZA in this age group is associated with significant overall response rates and OS rates at 1 or 2 years. There was no clear evidence of increased toxicity such as a higher hospitalization rate for infection or increased death rate before 4 cycles, when compared to similar patients aged less than 80.

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.