Original Study Poor Outcome of Patients With Myelodysplastic Syndrome After Azacitidine Treatment Failure Vu H. Duong, 1 Karen Lin, 2 Tea Reljic, 3 Ambuj Kumar, 3 Najla H. Al Ali, 2 Jeffrey E. Lancet, 2 Alan F. List, 2 Rami S. Komrokji 2 Abstract For patients with higher-risk myelodysplastic syndrome (MDS), treatment with azacitidine yields a meaningful survival benefit. However, most responders experience disease progression within 2 years. In our retrospective review of 59 patients in whom azacitidine therapy had failed, outcome was poor. Subsequent treatment with intensive chemotherapy or decitabine resulted in disappointing response rates, emphasizing the importance of prioritizing consideration for clinical trials. Background: Limited data have been reported describing the outcome and prognosis of patients with MDS in whom treatment with azanucleosides has failed. We report our single-institutional experience of patients with higher-risk MDS in whom therapy with azacitidine has failed. Patients and Methods: This was a retrospective study of MDS patients treated at the Moffitt Cancer Center in whom azacitidine treatment regimens had failed. Patients were identified through the Moffitt database, and clinical data were extracted. Azacitidine failure was defined as failure to achieve hematologic improvement or better after at least 4 cycles of therapy, loss of response, or disease progression during therapy. The objectives were to characterize response to salvage therapies after azacitidine failure and to estimate the overall survival. All responses were defined according to the International Working Group 2006 criteria, and survival was estimated using the Kaplan-Meier method. Results: A total of 59 patients in whom azacitidine treatment had failed were identified. The median age at treatment failure was 68 years, and most were Caucasian male patients. Thirteen patients received intensive chemotherapy with an overall response rate of 31%. Six patients were treated with decitabine, and none responded. Median overall survival of the entire cohort after azacitidine failure was 5.8 months (95% confidence interval, 1.3-10.3 months), with an estimated 12-month survival of 17%. Conclusion: Patients with higher-risk MDS in whom azacitidine treatment has failed have a poor prognosis and low probability of response to salvage treatments. The standard of care after azanucleoside failure should be enrollment in clinical trials. Clinical Lymphoma, Myeloma & Leukemia, Vol. 13, No. 6, 711-5 ª 2013 Elsevier Inc. All rights reserved. Keywords: Azacitidine failure, Azanucleosides, Decitabine, Higher risk, MDS Introduction The myelodysplastic syndromes (MDS) encompass a group of heterogeneous hematopoietic stem cell malignancies characterized by ineffective hematopoiesis, peripheral blood cytopenias, cytologic atypia, and a variable risk of progression to acute myeloid leukemia (AML). 1 Median survival for patients with de novo disease ranges from more than 10 years to approximately 6 months in those with the highest-risk disease. 2-4 Within the past decade, the azanucleo- side analogues, azacitidine and decitabine, were shown to have clinical activity, leading to their approval by the US Food and Drug Administration (FDA). These agents are nucleoside analogues that have dual mechanisms of action that include genomic hypomethylation-restoring expression of silenced genes and direct cytotoxicity. Azacitidine and decitabine are generally well tolerated and are widely used in the treatment of MDS. In phase III studies, deci- tabine was associated with complete remission rates of 9% to 13%, with partial response rates of 6% to 8% and a trend toward improved survival, especially in higher-risk patients. 5,6 Azacitidine Presented, in part, at the American Society of Hematology 2010 meeting (abstract 2913) 1 University of Maryland Greenebaum Cancer Center, Baltimore, MD 2 Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 3 College of Medicine, Center for Evidence Based Medicine, University of South Florida, Tampa, FL Submitted: Apr 16, 2013; Revised: Jul 8, 2013; Accepted: Jul 29, 2013; Epub: Sep 17, 2013 Address for correspondence: Rami S. Komrokji, MD, Department of Hematologic Malignancies, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL 33612 E-mail contact: Rami.komrokji@moffitt.org 2152-2650/$ - see frontmatter ª 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clml.2013.07.007 Clinical Lymphoma, Myeloma & Leukemia December 2013 - 711