Efficacy, Tolerability and Cost Benefit of a 5-Day Azacitidine Regimen

Azacitidine is a hypomethylating agent indicated for treatment of higher risk Myelodysplastic Syndromes (MDS). A recently published phase III trial demonstrated improved overall survival (OS) of MDS patients treated with Azacitidine compared to those receiving conventional care regimens, thus establishing this treatment option as first line therapy in those patients for whom bone marrow transplantation is not an option. Standard regime has been 75 mg /m²/day during 7 days; however several other treatment schedules have been explored that may have equal efficacy and tolerability though being more cost-effective.

Evaluate the efficacy of Azacitidine regimen in terms of transfusion independence (TI), overall response (OR), AML transformation and tolerability in patients with higher risk MDS and AML with dysplasia.

Higher risk (IPSS INT-2 and high risk) MDS patients were treated at a single institution with Azacitidine with a dosing regime of 500 mg/m² every 4 weeks administered over 5 days. The total dose was adjusted so that entire vials were used. OR, including complete response (CR), haematological response (HR) and partial response (PR) and TI, defined according to the 2000 International Working Group Criteria (IWG), were assessed by blood and bone marrow examination. Treatment cycles were repeated until toxicity or disease progression.

A total of 38 patients were treated with Azacitidine between January 2007 and December 2010. Mean age was 68 years old (range 85–33) and male sex was predominant (M:F of 1.5) Fifteen patients had refractory anaemia with excess blasts, eleven had AML with dysplasia, five had chronic myelomonocytic leukaemia, tree had refractory cytopenias with multilineage dysplasia and four had acute erythroblastic leukemia. Most patients were high risk according to IPSS scoring (82%). Azacytidine was used as first line therapy in 32% and as second line in 61%.

An average of 5 cycles (1–22) per patient were administered. The TI rate was of 45%, with average response duration of 6.5 months. OR rate was of 32% (9 CR, 1 HR and 2 PR). Twenty-two patients died during the follow-up period. Six patients progressed to AML: five of them had never shown any response to Azacitidine, while the other one had obtained TI.

Median survival from diagnosis was of 22 months, while median survival from beginning of treatment was of 12 months.

Tolerability was good, mainly grades I and II gastrointestinal and skin toxicity. Eleven patients (26%) had Grade III haematological toxicity and four (11%) suffered Grade IV haematological toxicity.

The Azacitidine schedule using 500 mg/m²/4 weeks with the total dose adjusted across the 5 days in order to avoid wastage, instead of 75 mg/m²/day during 7 days, allowed for significant costs reductions.

The efficacy of Azacitidine in achieving TI and prolonging survival in MDS is well recognized. In this study, Azacitidine improved quality of life and overall survival regardless of the quality of response. Treatment was well tolerated, with limited toxicity. Our results, though coming from a small group of patients, were comparable to what reported in the literature in terms of efficacy and tolerability, and we showed that it is cost effective to use our schedule regime.

Almeida:Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau.