Abstract
Background: Azacitidine (Vidaza®) is an effective and safe treatment (Tx) for patients (pts) with MDS (
Methods: In this phase II multicenter, open-label trial, MDS pts were randomized to 1 of 3 regimens administered every 4 weeks for 6 cycles: AZA 5-2-2 (75 mg/m²/day x 5 days, followed by 2 days no Tx, followed by 75 mg/m²/day x 2 days); AZA 5-2-5 (50 mg/m²/day x 5 days, followed by 2 days no Tx, followed by 50 mg/m²/day x 5 days); or AZA 5 (75 mg/m²/day x 5 days). Major and minor hematologic improvements (HI) were assessed by International Working Group (IWG) criteria (
Results: A total of 151 pts were randomized to Tx with AZA 5-2-2 (n=50), AZA 5-2-5 (n=51), or AZA 5 (n=50). Most pts are FAB classification RA/RARS (57%) or RAEB (30%). Of the 139 pts (92%) who received ≥56 days of Tx and are IWG evaluable, 74 pts (49%) completed ≥6 Tx cycles. The median number of Tx cycles across all Tx arms was 6. Of IWG-evaluable pts, 71 (51%) experienced HI (Table). The proportions of red blood cell (RBC) transfusion-dependent pts who achieved transfusion independence were AZA 5-2-2: 55% (12/22), AZA 5-2-5: 60% (12/20), and AZA-5: 67% (16/24). In FAB low-risk (RA/RARS) transfusion-dependent pts at baseline, RBC transfusion independence was reached by 60% (9/15), 56% (5/9), and 61% (11/18), respectively. No Tx-related mortality has been reported. Most grades 3 and 4 Tx-related AEs were hematological (AZA 5-2-2: 44%, AZA 5-2-5: 33%, AZA 5: 18%).
Conclusions: Independent of the alternative dosing regimen, the results of the initial 6-cycle Tx phase demonstrate a consistent response for HI, RBC transfusion independence, and safety profile across a broad range of MDS pts, including FAB low-risk pts. These results appear similar to those with the approved FDA regimen and further support the benefit of azacitidine in pts who are transfusion-dependent. Eligible pts continue to receive Tx during the ongoing 12-month maintenance phase of the study.
Major Hematologic Improvement in IWG Evaluable Pts (N=139)
| Major HI . | AZA 5-2-2 (N=46) . | AZA 5-2-5 (N=44) . | AZA 5 (N=49) . |
|---|---|---|---|
| *Includes major and minor HI; pts counted only once for best response in an improvement category. | |||
| n (%) (95% CI) | n (%) (95% CI) | n (%) (95% CI) | |
| Erythroid | 15 (33) (20, 48) | 17 (39) (24, 55) | 19 (39) (25, 54) |
| Platelet | 10 (22) (11, 36) | 8 (18) (8, 33) | 9 (18) (9, 32) |
| Neutrophil | 3 (7) (29, 100) | 4 (9) (40, 100) | 4 (8) (40, 100) |
| Any HI* | 20 (44) (29, 59) | 23 (52) (37, 68) | 28 (57) (42, 71) |
| Major HI . | AZA 5-2-2 (N=46) . | AZA 5-2-5 (N=44) . | AZA 5 (N=49) . |
|---|---|---|---|
| *Includes major and minor HI; pts counted only once for best response in an improvement category. | |||
| n (%) (95% CI) | n (%) (95% CI) | n (%) (95% CI) | |
| Erythroid | 15 (33) (20, 48) | 17 (39) (24, 55) | 19 (39) (25, 54) |
| Platelet | 10 (22) (11, 36) | 8 (18) (8, 33) | 9 (18) (9, 32) |
| Neutrophil | 3 (7) (29, 100) | 4 (9) (40, 100) | 4 (8) (40, 100) |
| Any HI* | 20 (44) (29, 59) | 23 (52) (37, 68) | 28 (57) (42, 71) |
Author notes
Disclosure:Employment: H. McIntyre, I. Fernando, J. Backstrom, and C.L. Beach are employees of Pharmion Corporation. Consultancy: R. Lyons. Ownership Interests:; H. McIntyre, I. Fernando, J. Backstrom, and C.L. Beach. Research Funding: R. Lyons: study only. Honoraria Information: T. Cosgriff: honorarium for Vidaza workshop in 2006, Las Vegas NV, Membership Information: R. Lyons: Pharmion advisory committee. Off Label Use: Yes, dosing regimens are different from the approved prescribing information.
