Clinical Experience with Azacitidine In Secondary Myelodysplastic Syndrome In Spain

Secondary myelodysplastic syndromes (MDS) and acute leukemias are some of the most serious adverse side effects in the treatment with chemotherapy or radiotherapy, as those therapies affect the DNA methylation profile of different tissues. New data suggest that abnormalities in the DNA methylation profile would contribute to secondary leukemogenesis. In general, secondary MDS has a worse prognosis than de novo MDS. Azacitidine (AZA) is an hypomethylating agent approved in Europe for the treatment of MDS, based on the AZA-00 clinical trial. No secondary MDS was included in this trial. Until its approval in May 2009, AZA was used in Spain under compasionate use in clinical trials.

Retrospective, longitudinal, multicenter Spanish study of data, promoted by the Hematology and Hematotherapy Andalusian Asociation and the Andalusian Group of MDS, on the course and management of patients treated with AZA under compasionate use. We present the analysis of clinical data of the 30 patients with Secondary MDS included in the registry.

Median age at diagnosed was 76 years. Male/female ratio: 13/17. ECOG performance status score 0–1 was 60%. The most frequently used initial dose of AZA was 75 mg/m2 in cycles of 28 days, administered subcutaneously (80%). The mean received cycles was 6. Overall response to treatment was 46.6% (International Working Group 2006 criteria): 16% complete response, 3.3% complete medullary response, 6.6% partial response and 20% hematological response. In addition, 23.3% had stable disease. AZA was generally tolerated well. The 3–4 grade adverse events documented in these patients were: Neutropenia (26%), thrombocytopenia (33%), anemia (20%), febrile neutropenia (3%), rash (6%), lumbar pain like colic type (3%) and subcutaneous reaction at the injection area (6%). Similar response ranges were found in patients with primary and secondary MDS, both within the registry as well as in the published literature.

Our results show that patients with secondary MDS respond to AZA in the same manner as the primary patients do, although their prognosis is traditionally worse. These favorable results in secondary MDS suggest that these patients respond to the hypomethylating treatment, probably by the DNA methylation alterations involved in the leukemogenesis. More data from this registry and from different clinical trials are needed to confirm these data, and complete answers with survival analyses.

García:Celgene : Research Funding.