Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes

Abstract

Background: In the AZA-001 trial, azacitidine (75 mg/m(2) /d subcutaneously for Days 1-7 of every 28-day cycle) demonstrated improved survival compared with conventional care regimens in patients with International Prognostic Scoring System-defined intermediate-2- or high-risk myelodysplastic syndrome and World Health Organization-defined acute myeloid leukemia with 20% to 30% bone marrow blasts.

Methods: This secondary analysis of the AZA-001 phase 3 study evaluated the time to first response and the potential benefit of continued azacitidine treatment beyond first response in responders.

Results: Overall, 91 of 179 patients achieved a response to azacitidine; responding patients received a median of 14 treatment cycles (range, 2-30). Median time to first response was 2 cycles (range, 1-16). Although 91% of first responses occurred by 6 cycles, continued azacitidine improved response category in 48% of patients. Best response was achieved by 92% of responders by 12 cycles. Median time from first response to best response was 3.5 cycles (95% confidence interval [CI], 3.0-6.0) in 30 patients who ultimately achieved a complete response, and 3.0 cycles (95% CI, 1.0-3.0) in 21 patients who achieved a partial response.

Conclusions: Continued azacitidine therapy in responders was associated with a quantitative increase in response to a higher response category in 48% of patients, and therefore may enhance clinical benefit in patients with higher-risk MDS.

Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

The study was funded by Celgene Corporation. The authors received editorial/writing support provided by Excerpta Medica in the preparation of the manuscript, funded by Celgene Corporation. The authors are fully responsible for content and editorial decisions for this article. Arlene Swern, PhD and David McKenzie, MS of Celgene Corporation provided statistical support to the authors during manuscript development. We thank Jay Backstrom, MD and C. L. Beach, PharmD from Celgene Corporation for their assistance with manuscript development. Financial disclosures: L. R. Silverman: honoraria, Celgene; P. Fenaux: honoraria, Amgen, Celgene, Cephalon, GSK, Johnson & Johnson, Roche, and MSD; research funding, Celgene and Roche; G. J. Mufti: honoraria, speaker’s bureau, and research funding, Amgen and Celgene; V. Santini: honoraria, Celgene and Novartis; E. Hellström-Lindberg: consultancy and research funding, Celgene; N. Gattermann: research funding and honoraria, Celgene and Novartis; G. Sanz: advisory committee member, honoraria, and research funding, Celgene; A. F. List: research funding and honoraria, Celgene; S. D. Gore: consultancy, equity ownership, and research funding, Celgene; J. F. Seymour: research funding, honoraria, speaker’s bureau, and advisory committee member, Celgene.

Copyright © 2011 American Cancer Society.

Figures

Figure 1

Time to first response (complete response [CR], partial response [PR], or hematological improvement [HI]) in patients who achieved a response during treatment with azacitidine is shown.

Figure 2

Time to best response after first response in patients treated with azacitidine is shown. The vertical line on the y-axis represents the 52% of patients whose first response was their best response. The remaining 48% of patients had an improvement in their first response with continued azacitidine therapy; they all improved from a first response of hematological improvement (HI) to either partial response (PR) or complete response (CR).