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 (

). The current treatment paradigm, which is based on a relationship between complete remission (CR) and survival, is increasingly being questioned (
). Results of AZA-001 show CR is sufficient but not necessary to prolong OS (
J Clin Oncol
;abstr 7006
). Indeed, the AZA CR rate in AZA-001 was modest (17%), while partial remission (PR, 12%) and hematologic improvement (HI, 49%) were also predictive of prolonged survival. This analysis was conducted to assess the median number of AZA treatment cycles associated with achievement of first response, as measured by IWG 2000-defined CR, PR, or HI (major + minor). The number of treatment cycles from first response to best response was also measured.

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.

Disclosures: Silverman:Celgene: Speakers Bureau. Fenaux:Celgene: Consultancy, Honoraria, Research Funding; Ortho Biotech: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria, Research Funding. Mufti:Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Santini:Celgene: Honoraria; Novartis: Honoraria; J&J: Honoraria. Hellström-Lindberg:Celgene: Consultancy, Research Funding. Gattermann:Celgene: Research Funding, Speakers Bureau. Sanz:Celgene: Membership on an entity’s Board of Directors or advisory committees. List:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Gore:Celgene: Consultancy, Equity Ownership, Research Funding. Seymour:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Backstrom:Celgene: Employment. McKenzie:Celgene: Employment. Beach:Celgene: Employment.

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