The Effects of Continued Azacitidine (AZA) Treatment Cycles on Response in Higher-Risk Patients (Pts) with Myelodysplastic Syndromes (MDS)

Background. The international, phase III, multicenter AZA-001 trial demonstrated AZA is the first treatment to significantly extend overall survival (OS) in higher-risk MDS pts (

Methods. Pts with higher-risk MDS (FAB: RAEB, RAEB-T, or CMML, and IPSS: Int-2 or High) were included. Pts were randomized to AZA (75 mg/m²/d SC × 7d q 28d) or to a conventional care regimen (CCR). AZA treatment was continued until disease progression (or unacceptable toxicity), regardless of hematologic response. Erythropoiesis stimulating agents were not allowed.

Results. In all, 358 pts were randomized (179 to AZA and 179 to CCR). Of the 179 AZA pts, 91 (51%) achieved a CR, PR, or HI. For the 91 pts who achieved an IWG response, the median number of cycles to first response was 3 (range: 1 – 22), 81% of pts achieved a first response by 6 cycles, and 90% achieved a first response by 9 cycles. For 57% of responders (n=52), their first response was their best response; the remaining 43% (n=39) had an improvement in their response status at a median of approximately 4 additional treatment cycles (range 1–11 treatment cycles) after their first response.

Conclusions. While many pts achieving a hematologic response with AZA do so in early treatment cycles, continued AZA dosing can further improve pt responses. In the AZA-001 study, a significant OS benefit was observed compared with CCR. In this study, AZA pts received a median of 9 treatment cycles (range 1–39). For those achieving a response of HI or better, 90% did so by 9 cycles; more than 40% of responders later achieved an improved response. In the absence of unacceptable toxicity or disease progression, continued AZA treatment is appropriate and may maximize patient benefit.